Review Article Chinese Herbal Compounds for the Prevention and...

16
Review Article Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms Qing Liu, 1,2 Jianping Li, 1 Adam Hartstone-Rose, 1 Jing Wang, 2 Jiqiang Li, 2 Joseph S. Janicki, 1 and Daping Fan 1 1 Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29208, USA 2 Guangdong Provincial Hospital of Chinese Medicine, e Second Clinical School of Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China Correspondence should be addressed to Daping Fan; [email protected] Received 19 August 2014; Accepted 15 October 2014 Academic Editor: Qunhao Zhang Copyright © 2015 Qing Liu et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Atherosclerosis is a leading cause of disability and death worldwide. Research into the disease has led to many compelling hypotheses regarding the pathophysiology of atherosclerotic lesion formation and the resulting complications such as myocardial infarction and stroke. Herbal medicine has been widely used in China as well as other Asian countries for the treatment of cardiovascular diseases for hundreds of years; however, the mechanisms of action of Chinese herbal medicine in the prevention and treatment of atherosclerosis have not been well studied. In this review, we briefly describe the mechanisms of atherogenesis and then summarize the research that has been performed in recent years regarding the effectiveness and mechanisms of antiatherogenic Chinese herbal compounds in an attempt to build a bridge between traditional Chinese medicine and cellular and molecular cardiovascular medicine. 1. Introduction Atherosclerosis is a disease of the arterial wall that occurs at susceptible sites in major arteries. It is initiated by endothelial injury and subsequent lipid retention and oxidation in the intima which then provokes chronic inflammation and ulti- mately causes stenosis or thrombosis [1]. During this progres- sion, residential arterial wall cells including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), as well as circulating leukocytes, especially monocytes/macrophages, are mainly involved. Atherosclerotic lesions can cause steno- sis with potentially lethal distal ischemia or, if ruptured, can trigger thrombotic occlusion of major arteries to the heart, brain, legs, and other organs [2]. A variety of risk factors may intensify or provoke atherosclerosis through their effects on endothelial function, low-density lipoprotein (LDL) con- centration and modification, and vascular wall inflammation. ese risk factors include hypertension, smoking, diabetes mellitus, obesity, and bacterial infection [3]. Traditional Chinese medicine (TCM), especially herbal medicine, has been used for the treatment of cardiovascular diseases for hundreds of years as documented in Inner Canon of Yellow Emperor and Synopsis of Golden Chamber. Also, the effectiveness of several extracts derived from Chinese herbs has been evaluated in recent years. However, the cellular and molecular details regarding the underlying effi- cacious mechanisms of Chinese herbal medicine in treating atherosclerosis have just begun to be understood. erefore, the purpose of this review is to first provide a brief description of the mechanisms of atherogenesis and then to summarize the recent research results regarding the effectiveness and mechanisms of antiatherogenic Chinese herbal compounds. 2. Mechanisms of Atherogenesis Atherogenesis is an inflammatory process, initiated by the retention of lipids in the subendothelial space of the vascular wall and encompasses a complex interaction among the Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2015, Article ID 752610, 15 pages http://dx.doi.org/10.1155/2015/752610

Transcript of Review Article Chinese Herbal Compounds for the Prevention and...

Page 1: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Review ArticleChinese Herbal Compounds for the Prevention and Treatmentof Atherosclerosis Experimental Evidence and Mechanisms

Qing Liu12 Jianping Li1 Adam Hartstone-Rose1 Jing Wang2 Jiqiang Li2

Joseph S Janicki1 and Daping Fan1

1 Department of Cell Biology and Anatomy University of South Carolina School of Medicine 6439 Garners Ferry RoadColumbia SC 29208 USA

2Guangdong Provincial Hospital of Chinese Medicine The Second Clinical School of MedicineGuangzhou University of Chinese Medicine Guangzhou 510405 China

Correspondence should be addressed to Daping Fan dapingfanuscmedscedu

Received 19 August 2014 Accepted 15 October 2014

Academic Editor Qunhao Zhang

Copyright copy 2015 Qing Liu et alThis is an open access article distributed under the Creative Commons Attribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Atherosclerosis is a leading cause of disability anddeathworldwide Research into the disease has led tomany compelling hypothesesregarding the pathophysiology of atherosclerotic lesion formation and the resulting complications such as myocardial infarctionand stroke Herbal medicine has been widely used in China as well as other Asian countries for the treatment of cardiovasculardiseases for hundreds of years however the mechanisms of action of Chinese herbal medicine in the prevention and treatment ofatherosclerosis have not been well studied In this review we briefly describe the mechanisms of atherogenesis and then summarizethe research that has been performed in recent years regarding the effectiveness and mechanisms of antiatherogenic Chineseherbal compounds in an attempt to build a bridge between traditional Chinese medicine and cellular andmolecular cardiovascularmedicine

1 Introduction

Atherosclerosis is a disease of the arterial wall that occurs atsusceptible sites inmajor arteries It is initiated by endothelialinjury and subsequent lipid retention and oxidation in theintima which then provokes chronic inflammation and ulti-mately causes stenosis or thrombosis [1] During this progres-sion residential arterial wall cells including endothelial cells(ECs) and vascular smooth muscle cells (VSMCs) as well ascirculating leukocytes especially monocytesmacrophagesare mainly involved Atherosclerotic lesions can cause steno-sis with potentially lethal distal ischemia or if ruptured cantrigger thrombotic occlusion of major arteries to the heartbrain legs and other organs [2] A variety of risk factorsmay intensify or provoke atherosclerosis through their effectson endothelial function low-density lipoprotein (LDL) con-centration andmodification and vascular wall inflammationThese risk factors include hypertension smoking diabetesmellitus obesity and bacterial infection [3]

Traditional Chinese medicine (TCM) especially herbalmedicine has been used for the treatment of cardiovasculardiseases for hundreds of years as documented in Inner Canonof Yellow Emperor and Synopsis of Golden Chamber Alsothe effectiveness of several extracts derived from Chineseherbs has been evaluated in recent years However thecellular and molecular details regarding the underlying effi-cacious mechanisms of Chinese herbal medicine in treatingatherosclerosis have just begun to be understood Thereforethe purpose of this review is to first provide a brief descriptionof the mechanisms of atherogenesis and then to summarizethe recent research results regarding the effectiveness andmechanisms of antiatherogenic Chinese herbal compounds

2 Mechanisms of Atherogenesis

Atherogenesis is an inflammatory process initiated by theretention of lipids in the subendothelial space of the vascularwall and encompasses a complex interaction among the

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 752610 15 pageshttpdxdoiorg1011552015752610

2 Evidence-Based Complementary and Alternative Medicine

modified lipoproteins residential vascular cells and immunesystem [4] The schematic in Figure 1 depicts the main stepsof atherogenesis In the following section the main elementsinvolved in the pathogenesis of atherosclerosis will be brieflydescribed

21 Hyperlipidemia Dyslipidemia is one of the main riskfactors leading to atherosclerosis [5] The lipid hypothesis ofatherogenesis states that abnormally elevated levels of plasmaLDL and low levels of plasma high density lipoproteins(HDL) are the primary causes of atherosclerosis [6ndash8] Thishypothesis has been strongly supported by the success ofstatin drug therapy which has significantly reduced coronaryartery disease mortality through lowering plasma LDL levelsduring the past 40 years [9] However the HDL wing ofthe hypothesis remains to be confirmed by successful HDL-targeting approaches A commonmechanism through whichhyperlipidemia causes atherosclerosis involves the accumula-tion of cholesteryl esters in macrophages of the arterial wall[10]

22 Endothelial Injury The response-to-injury hypothe-sis of atherogenesis states that endothelial injury triggerssubsequent interactions among all of the cells found inthe atherosclerosis lesions [11] Injured endothelium allowslipoproteins to migrate into subendothelial space Thistogether with the discovery of adhesion molecules expressedby endothelial cells (eg vascular cell adhesion molecule-1)provides important insight into the initiation of atheroscle-rotic lesions [12] That is increased expression of adhesionmolecules favors monocyte adhesion and penetration whichresults in accumulation of macrophages within the suben-dothelial space where they encounter lipoprotein particles[13]

23 LDL Subendothelial Retention and Oxidation Suben-dothelial retention of lipoproteins is a key early step inatherosclerosis provoking a cascade of adverse events to thepathogenic response [14] High levels of plasma lipids par-ticularly LDL and very-low density lipoproteins (VLDL) areamong the pathophysiologic stimuli that induce endothelialdysfunction Retention and modification of apolipoproteinB (apoB) containing lipoproteins LDL intermediate densitylipoprotein (IDL) and lipoprotein (a) [Lp(a)] in the arterialintima extracellular matrix (ECM) represent early events ofplaque development which is referred to as the ldquoresponse-to-retentionrdquo hypothesis [15]

The oxidation hypothesis of atherosclerosis suggests thatan early event in the development of atherosclerosis is anoxidative modification of LDL that significantly increasesits uptake into the arterial intima [16 17] Moreover lipidoverload may increase lipopolysaccharide (LPS) circulatinglevels and oxidative stress In particular the oxidation oflipoproteins that results from an imbalance of the pro- andantioxidant equilibrium is involved in the pathologic processof atherosclerotic alterations of cellular function Lipid oxida-tion induced by leukocyte-derived reactive oxygen speciesnot only promotes the growth and migration of smooth

muscle cells monocytesmacrophages and fibroblasts butalso amplifies foam cell formation through oxidized LDL(oxLDL) formation and uptake [18]

24 Monocyte Migration and Activation The overexpressionof inducible adhesion molecules results in the adherenceof mononuclear cells to the endothelial surface whereuponthey receive chemoattractant signals that beckon them toenter the intima With regard to the mechanisms thatmediate monocyte-derived macrophage maturation it hasbeen reported that macrophage colony-stimulating factor(M-CSF) induces scavenger receptors and promotes theproliferation of monocytes in early atherosclerotic lesions[19] Macrophages also contribute to the thrombotic compli-cations of atherosclerosis in pivotal ways These phagocytesfurnish the bulk of the enzymes (ie matrix metallopro-teinases MMPs) that catabolize collagen a key constituentof the fibrous cap of the plaque which when activatedpredisposes the plaque to rupture [20]

25 Vascular Smooth Muscle Cell (VSMC) Migration andProliferation In response to atherogenic stimuli VSMCsundergo a phenotypic switch from contractile phenotype tosynthetic and inflammatory phenotype the inflammatoryVSMCs migrate into intima and proliferate contributing tothe atherogenesis [21 22] VSMCs are the major producers ofECM within the vessel wall [23] and can modify the type ofmatrix proteins produced In turn the type of matrix presentcan affect the lipid content of the developing plaques andthe proliferative index of the cells that are adherent to themLike endothelial cells VSMCs can also express a variety ofadhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) to which monocytes and lymphocytes can adhere andmigrate into the vessel wall [24] Like macrophages VSMCscan also express a variety of receptors for lipid uptake andcan form foam-like cells thereby participating in the earlyaccumulation of plaque lipid [25]

26 FoamCell Formation Foamcellsmainly arise frommon-onuclear phagocytes although smooth muscle and endothe-lial cells can also become engorged with lipids Withinthe plaque the mononuclear phagocytes express scavengerreceptors (SRs) including CD36 SR-A and SR-BI Thesescavenger receptorsmediate the engulfment ofmodified LDLparticles that contribute to macrophage foam cell formation[26] Other receptors for native lipoprotein particles includ-ing LDLR VLDLR and LRP1 also contribute to foam cellformation As mentioned above VSMCs which acquire asynthetic and inflammatory phenotype in the plaque can alsotake up lipoproteins and transform into foamcells [27] Deathof foam cells leads to formation of a necrotic core whichserves as a depot for cellular debris and lipids [28]

27 Apoptosis and Efferocytosis and Unresolved InflammationAs atherosclerotic lesions evolve both the macrophage-derived and smooth muscle-derived foam cells can undergoprogrammed cell death or apoptosis [29] The death of foam

Evidence-Based Complementary and Alternative Medicine 3

Tunica media

SubendothelialspaceEndothelium

(a)

Injured endothelium

(b)

(c) (d)

Necrotic core

Fibrous cap

LDLOxidized LDLMonocyteSmooth muscle cell

MacrophageFoam cellApoptotic cell

(e)

Ruptured thrombus

B cellsT cellsMast cell

Dendritic cell

Extracellular matrixCholesterol crystals

(f)

Figure 1 A schematic drawing depicting the formation of atherosclerotic plaques (a) In the wall of a normal artery there is a very smallsubendothelial space in the intima between the endothelium and the smooth muscle cell layer in tunica media (b) Hyperlipidemia andendothelial injury lead to the infiltration of LDL particles into the subendothelial space (c) A large number of LDL particles are retainedand subsequently oxidized in the subendothelial space followed by monocyte infiltration (from lumen) and smooth muscle cell migration(from tunica media) (d) Monocytes and smooth muscle cells differentiate into macrophages which engulf LDL and turn into foam cells andare activated by oxidized LDL SMCs are also activated proliferate and transform into lipid-laden foam cells (e) Macrophage and smoothmuscle foam cells undergo apoptosis unbalanced apoptosisefferocytosis results in necrotic core formation and unresolved inflammationOther immune cell types also participate in the arterial wall inflammation (f) Erosion of the fibrous cap caused by the matrix degradingenzymes secreted by the macrophages leads to unstable plaques which eventually rupture and result in thrombus formation and adverseclinical events

4 Evidence-Based Complementary and Alternative Medicine

cells may not be a random event or the result of bursting likean overinflated balloon due to lipid overload Rather it maybe due in part to gradients of concentration of factors such asmacrophage colony-stimulating factor (M-CSF) required forsurvival of humanmonocytes [20] However some apoptoticcells may not disappear from the atherosclerotic lesions butinstead accumulate in a ldquomummifiedrdquo state [20] The elegantstudies of Ira Tabas have elaborated upon this concept ofimpaired clearance or ldquoefferocytosisrdquo of apoptotic cells inplaques which leads to unresolved inflammation [30] Theapoptotic foam cells that escape efferocytosis release theirlipid content to the extracellular space and contribute to lipidcore formation

Over the last dozen years appreciation of the role ofinflammation in atherosclerosis has burgeoned Intralesionalor extralesional inflammation may hasten atheroma evolu-tion and precipitate acute events Circulating acute-phasereactants elicited by inflammation not only may serve asa biomarker for increased risk of vascular events but alsoin some cases may contribute to their pathogenesis [31]Advances stemming from basic research have established afundamental role for inflammation in mediating all stagesof this disease from initiation through progression and ulti-mately to the thrombotic complications of atherosclerosis

The basic science of inflammatory biology applied toatherosclerosis has provided considerable insight into themechanisms underlying the recruitment of leukocytes Earlyafter the initiation of atherogenesis arterial endothelialcells begin to express on their surface selective adhesionmolecules that bind various classes of leukocytes [12] Inparticular VCAM-1 binds precisely the types of leukocytesinvolved in early atheroma the monocyte and T lymphocyteNot only does VCAM-1 expression increase on endothelialcells overlying nascent atheroma but defective VCAM-1shows interrupted lesion development [32] Once adheredto the endothelium leukocytes penetrate into the intima inresponse to chemoattractant molecules For example mono-cyte chemoattractant protein-1 (MCP-1) appears responsiblefor the direct migration of monocytes into the intima at sitesof lesion formation [33] Once resident in the arterial wall theblood-derived inflammatory cells participate in and perpetu-ate a local inflammatory response The macrophages expressscavenger receptors for modified lipoproteins permittingthem to ingest lipid and become foam cells In additionto MCP-1 macrophage colony-stimulating factor (M-CSF)contributes to the differentiation of the blood monocyte intothe macrophage foam cell [34] T cells likewise encountersignals that cause them to elaborate inflammatory cytokinessuch as tumor necrosis factor-120572 (TNF-120572) that in turn canstimulate macrophages as well as vascular endothelial cellsand SMCs [35] As this inflammatory process continues theactivated leukocytes and intrinsic arterial cells can releasefibrogenic mediators including a variety of peptide growthfactors that can promote replication of SMCs and contributeto elaboration by these cells of a dense ECM characteristic ofa more advanced atherosclerosis lesion Inflammatory pro-cesses not only promote initiation and evolution of atheromabut also contribute decisively to precipitating the acutethrombotic complications of atheroma [3] The activated

macrophages abundant in atheroma can produce proteolyticenzymes capable of degrading the collagen that lends strengthto the plaquersquos protective fibrous cap rendering the cap thinweak and susceptible to rupture Inflammatory mediatorsregulate tissue factor expression by plaque macrophagesdemonstrating an essential link between arterial inflamma-tion and thrombosis [36]

Both innate and adaptive immunity are involved inatherosclerosis Inflammation per se can drive arterial hyper-plasia even in the absence of traditional risk factors [37]Cytokines as inflammatorymessengers provide amechanismwhereby risk factors for atherosclerosis can alter arterialbiology Inflammation regulates aspects of plaque biologythat trigger the thrombotic complications of atheroscle-rosis [38] Overall inflammatory mediators participate inall phases of atherogenesis from lesion initiation throughprogression and ultimately to the clinical complications ofthis disease The fact that all types of immune cells have beenfound in atherosclerotic plaques indicates that all immunecomponents may participate in atherogenesis All of thesefactors form the basis of the ldquoinflammatory hypothesisrdquo

3 Effects and Mechanisms of ChineseHerb Compounds in the Attenuation ofAtherosclerosis

An early description of the clinical manifestations andtreatment of atherosclerosis can be found in the classictraditional Chinese medicine book Inner Canon of YellowEmperor which was completed around 500 BC In the theoryof traditional Chinese medicine atherosclerosis is usuallyreferred to as ldquoMaiBirdquo a vascular problem that is caused byQistagnation Blood stasis andor coagulated Phlegm in whichQi stands for the energy Blood stands for the material andPhlegm stands for a kind of pathological product For overtwo thousand years atherosclerosis and its resulting heartdisease have been treated with numerous herbal remediesWhile somewhat effective these herbal remedies have notbeen well studied using evidence-based approaches or usingmodern cellular and molecular techniques Recently how-ever investigations to examine the effects andmechanisms ofsingle herbal compounds in the modulation of atherogenesishave occurred A summary of these studies is presented inthe following section wherein the compounds are discussedaccording to their site of activity

31 Chinese Herbal Compounds with Endothelial ProtectiveActivity (Table 1) The study by Lee et al demonstratedthat pretreatment of human umbilical vein endothelial cells(HUVEC) with Buddleja Officinalis (BO 1ndash10microgmL)for 18 hrs dose-dependently inhibited TNF-120572-induced adhe-sion U937 monocytic cells as well as mRNA and proteinexpressions of VCAM-1 and ICAM-1 Pretreatment withBO also blocked TNF-120572-induced reactive oxygen species(ROS) formation Nuclear factor-kappa B (NF-kappa B) isrequired for the transcription of these adhesion moleculegenes [43] Wan et al found that Panax notoginseng saponins(PNS) derived from the Chinese herb Panax notoginseng

Evidence-Based Complementary and Alternative Medicine 5

Table 1 Chinese herbal compounds with endothelial protective activity

Compound Herb Target or indicator Type of study Reference

Resveratrol Rhizoma polygonumcuspidatum cav-1 VEGF KDR In vitro [39]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO E-selectin

VCAM-1 ICAM-1 ET-1 In vivo [40]

Protocatechuicaldehyde

Salvia miltiorrhizaBunge

Caspase-3 caspase-2 Bcl-2Baxcytochrome c caspase-9granzyme B

In vitro [41]

Cryptotanshinone Salvia miltiorrhizaBunge

oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Panax notoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo bilobaextract Ginkgo biloba VCAM-1 ICAM-1 E-selectin

ROS RSTF Both [46 47]

Salvia miltiorrhiza Salvia miltiorrhizaBunge

eNOS NO NADPH oxidasesubunit Nox4 In vitro [48]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Magnolol Magnolia officinalis

IL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyteadhesion cyclin D1 MCP-1NF-kB VCAM-1

Both [50 51]

Aqueous extract ofSalvia miltiorrhiza

Salvia miltiorrhizaBunge ICAM-1 VCAM-1 GSH NF-120581B In vitro [52]

Salvianolic acid B Salvia miltiorrhizaBunge ICAM-1 E-selectin NF-120581B In vitro [53]

dose-dependently inhibited monocyte adhesion to activatedendothelium as well as the expression of TNF-120572-inducedendothelial adhesionmolecules such as ICAM-1 andVCAM-1 [45] Recent findings reported by Tian et al indicatedthat Resveratrol a compound derived from the Chineseherb Rhizoma polygonum cuspidatum downregulated theincreased expressions of vascular endothelial growth factor(VEGF) and kinase insert domain receptor (KDR or VEGFreceptor-2) [39] Results from Choi et al showed that extractfrom Cynanchum wilfordii (ECW) treatment significantlydecreased vascular inflammation through an inhibition ofcellular adhesionmolecules such as E-selectin VCAM-1 andICAM-1 as well as endothelin-1 (ET-1) expression [40]

32 Chinese Herbal Compounds That Lower Lipids and Anti-oxidation (Tables 2 and 3) Zhang et al [54] using a plasmalipid analysis approach found Celastrus orbiculatus ThunbExtract (COT) a compound derived from the Chinese herbCelastrus orbiculatus Thunb to decrease total cholesterol(TC) non-high-density lipoprotein cholesterol (non-HDL-C) triglyceride (TG) apolipoprotein B100 (apoB100) andapolipoprotein E (apoE) levels and to increase the levelof HDL cholesterol (HDL-C) Quantitative real-time PCRrevealed that COTupregulated themRNA abundance of LDLreceptor (LDL-R) scavenger receptor class B type 1 (SR-B1)

cholesterol 7120572-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [54] Choi et alreported that extract from the herb Cynanchum wilfordiitreatment in HFCD-fed rats lessened LDL cholesterol andtriglyceride levels and elevated HDL cholesterol [40] Resultsfrom Subramaniam et al indicated that the ethanolic fractionof the herb T arjuna significantly decreased TC LDL andTG levels increased HDL and lessened the number of aorticatherosclerotic lesions [57] Dinani et al demonstrated theability of the extract from the Chinese herbArtemisia aucherito significantly reduce the levels of TC LDL cholesterol andTG and to increase HDL cholesterol [58]

Li et al discovered that Farrerol an extract from theChinese herbRhododendron dauricum L significantly inhib-ited the H

2O2-induced loss of cell viability and enhanced

superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) activities in EAhy926 cells In addition Far-rerol inhibited the H

2O2-induced elevation in the levels of

intracellular malondialdehyde (MDA) and reactive oxygenspecies (ROS) [63] Chen et al reported that treatment withSalvianolic acid B (Sal B) a main compound derived from theherb Salvia miltiorrhiza Bunge suppressed ERK12 and JNKphosphorylation and attenuated the increase in prostaglandinE2 production and NADPH oxidase activity in LPS-treatedhuman aortic smoothmuscle cells (HASMCs) indicating that

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 2: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

2 Evidence-Based Complementary and Alternative Medicine

modified lipoproteins residential vascular cells and immunesystem [4] The schematic in Figure 1 depicts the main stepsof atherogenesis In the following section the main elementsinvolved in the pathogenesis of atherosclerosis will be brieflydescribed

21 Hyperlipidemia Dyslipidemia is one of the main riskfactors leading to atherosclerosis [5] The lipid hypothesis ofatherogenesis states that abnormally elevated levels of plasmaLDL and low levels of plasma high density lipoproteins(HDL) are the primary causes of atherosclerosis [6ndash8] Thishypothesis has been strongly supported by the success ofstatin drug therapy which has significantly reduced coronaryartery disease mortality through lowering plasma LDL levelsduring the past 40 years [9] However the HDL wing ofthe hypothesis remains to be confirmed by successful HDL-targeting approaches A commonmechanism through whichhyperlipidemia causes atherosclerosis involves the accumula-tion of cholesteryl esters in macrophages of the arterial wall[10]

22 Endothelial Injury The response-to-injury hypothe-sis of atherogenesis states that endothelial injury triggerssubsequent interactions among all of the cells found inthe atherosclerosis lesions [11] Injured endothelium allowslipoproteins to migrate into subendothelial space Thistogether with the discovery of adhesion molecules expressedby endothelial cells (eg vascular cell adhesion molecule-1)provides important insight into the initiation of atheroscle-rotic lesions [12] That is increased expression of adhesionmolecules favors monocyte adhesion and penetration whichresults in accumulation of macrophages within the suben-dothelial space where they encounter lipoprotein particles[13]

23 LDL Subendothelial Retention and Oxidation Suben-dothelial retention of lipoproteins is a key early step inatherosclerosis provoking a cascade of adverse events to thepathogenic response [14] High levels of plasma lipids par-ticularly LDL and very-low density lipoproteins (VLDL) areamong the pathophysiologic stimuli that induce endothelialdysfunction Retention and modification of apolipoproteinB (apoB) containing lipoproteins LDL intermediate densitylipoprotein (IDL) and lipoprotein (a) [Lp(a)] in the arterialintima extracellular matrix (ECM) represent early events ofplaque development which is referred to as the ldquoresponse-to-retentionrdquo hypothesis [15]

The oxidation hypothesis of atherosclerosis suggests thatan early event in the development of atherosclerosis is anoxidative modification of LDL that significantly increasesits uptake into the arterial intima [16 17] Moreover lipidoverload may increase lipopolysaccharide (LPS) circulatinglevels and oxidative stress In particular the oxidation oflipoproteins that results from an imbalance of the pro- andantioxidant equilibrium is involved in the pathologic processof atherosclerotic alterations of cellular function Lipid oxida-tion induced by leukocyte-derived reactive oxygen speciesnot only promotes the growth and migration of smooth

muscle cells monocytesmacrophages and fibroblasts butalso amplifies foam cell formation through oxidized LDL(oxLDL) formation and uptake [18]

24 Monocyte Migration and Activation The overexpressionof inducible adhesion molecules results in the adherenceof mononuclear cells to the endothelial surface whereuponthey receive chemoattractant signals that beckon them toenter the intima With regard to the mechanisms thatmediate monocyte-derived macrophage maturation it hasbeen reported that macrophage colony-stimulating factor(M-CSF) induces scavenger receptors and promotes theproliferation of monocytes in early atherosclerotic lesions[19] Macrophages also contribute to the thrombotic compli-cations of atherosclerosis in pivotal ways These phagocytesfurnish the bulk of the enzymes (ie matrix metallopro-teinases MMPs) that catabolize collagen a key constituentof the fibrous cap of the plaque which when activatedpredisposes the plaque to rupture [20]

25 Vascular Smooth Muscle Cell (VSMC) Migration andProliferation In response to atherogenic stimuli VSMCsundergo a phenotypic switch from contractile phenotype tosynthetic and inflammatory phenotype the inflammatoryVSMCs migrate into intima and proliferate contributing tothe atherogenesis [21 22] VSMCs are the major producers ofECM within the vessel wall [23] and can modify the type ofmatrix proteins produced In turn the type of matrix presentcan affect the lipid content of the developing plaques andthe proliferative index of the cells that are adherent to themLike endothelial cells VSMCs can also express a variety ofadhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) to which monocytes and lymphocytes can adhere andmigrate into the vessel wall [24] Like macrophages VSMCscan also express a variety of receptors for lipid uptake andcan form foam-like cells thereby participating in the earlyaccumulation of plaque lipid [25]

26 FoamCell Formation Foamcellsmainly arise frommon-onuclear phagocytes although smooth muscle and endothe-lial cells can also become engorged with lipids Withinthe plaque the mononuclear phagocytes express scavengerreceptors (SRs) including CD36 SR-A and SR-BI Thesescavenger receptorsmediate the engulfment ofmodified LDLparticles that contribute to macrophage foam cell formation[26] Other receptors for native lipoprotein particles includ-ing LDLR VLDLR and LRP1 also contribute to foam cellformation As mentioned above VSMCs which acquire asynthetic and inflammatory phenotype in the plaque can alsotake up lipoproteins and transform into foamcells [27] Deathof foam cells leads to formation of a necrotic core whichserves as a depot for cellular debris and lipids [28]

27 Apoptosis and Efferocytosis and Unresolved InflammationAs atherosclerotic lesions evolve both the macrophage-derived and smooth muscle-derived foam cells can undergoprogrammed cell death or apoptosis [29] The death of foam

Evidence-Based Complementary and Alternative Medicine 3

Tunica media

SubendothelialspaceEndothelium

(a)

Injured endothelium

(b)

(c) (d)

Necrotic core

Fibrous cap

LDLOxidized LDLMonocyteSmooth muscle cell

MacrophageFoam cellApoptotic cell

(e)

Ruptured thrombus

B cellsT cellsMast cell

Dendritic cell

Extracellular matrixCholesterol crystals

(f)

Figure 1 A schematic drawing depicting the formation of atherosclerotic plaques (a) In the wall of a normal artery there is a very smallsubendothelial space in the intima between the endothelium and the smooth muscle cell layer in tunica media (b) Hyperlipidemia andendothelial injury lead to the infiltration of LDL particles into the subendothelial space (c) A large number of LDL particles are retainedand subsequently oxidized in the subendothelial space followed by monocyte infiltration (from lumen) and smooth muscle cell migration(from tunica media) (d) Monocytes and smooth muscle cells differentiate into macrophages which engulf LDL and turn into foam cells andare activated by oxidized LDL SMCs are also activated proliferate and transform into lipid-laden foam cells (e) Macrophage and smoothmuscle foam cells undergo apoptosis unbalanced apoptosisefferocytosis results in necrotic core formation and unresolved inflammationOther immune cell types also participate in the arterial wall inflammation (f) Erosion of the fibrous cap caused by the matrix degradingenzymes secreted by the macrophages leads to unstable plaques which eventually rupture and result in thrombus formation and adverseclinical events

4 Evidence-Based Complementary and Alternative Medicine

cells may not be a random event or the result of bursting likean overinflated balloon due to lipid overload Rather it maybe due in part to gradients of concentration of factors such asmacrophage colony-stimulating factor (M-CSF) required forsurvival of humanmonocytes [20] However some apoptoticcells may not disappear from the atherosclerotic lesions butinstead accumulate in a ldquomummifiedrdquo state [20] The elegantstudies of Ira Tabas have elaborated upon this concept ofimpaired clearance or ldquoefferocytosisrdquo of apoptotic cells inplaques which leads to unresolved inflammation [30] Theapoptotic foam cells that escape efferocytosis release theirlipid content to the extracellular space and contribute to lipidcore formation

Over the last dozen years appreciation of the role ofinflammation in atherosclerosis has burgeoned Intralesionalor extralesional inflammation may hasten atheroma evolu-tion and precipitate acute events Circulating acute-phasereactants elicited by inflammation not only may serve asa biomarker for increased risk of vascular events but alsoin some cases may contribute to their pathogenesis [31]Advances stemming from basic research have established afundamental role for inflammation in mediating all stagesof this disease from initiation through progression and ulti-mately to the thrombotic complications of atherosclerosis

The basic science of inflammatory biology applied toatherosclerosis has provided considerable insight into themechanisms underlying the recruitment of leukocytes Earlyafter the initiation of atherogenesis arterial endothelialcells begin to express on their surface selective adhesionmolecules that bind various classes of leukocytes [12] Inparticular VCAM-1 binds precisely the types of leukocytesinvolved in early atheroma the monocyte and T lymphocyteNot only does VCAM-1 expression increase on endothelialcells overlying nascent atheroma but defective VCAM-1shows interrupted lesion development [32] Once adheredto the endothelium leukocytes penetrate into the intima inresponse to chemoattractant molecules For example mono-cyte chemoattractant protein-1 (MCP-1) appears responsiblefor the direct migration of monocytes into the intima at sitesof lesion formation [33] Once resident in the arterial wall theblood-derived inflammatory cells participate in and perpetu-ate a local inflammatory response The macrophages expressscavenger receptors for modified lipoproteins permittingthem to ingest lipid and become foam cells In additionto MCP-1 macrophage colony-stimulating factor (M-CSF)contributes to the differentiation of the blood monocyte intothe macrophage foam cell [34] T cells likewise encountersignals that cause them to elaborate inflammatory cytokinessuch as tumor necrosis factor-120572 (TNF-120572) that in turn canstimulate macrophages as well as vascular endothelial cellsand SMCs [35] As this inflammatory process continues theactivated leukocytes and intrinsic arterial cells can releasefibrogenic mediators including a variety of peptide growthfactors that can promote replication of SMCs and contributeto elaboration by these cells of a dense ECM characteristic ofa more advanced atherosclerosis lesion Inflammatory pro-cesses not only promote initiation and evolution of atheromabut also contribute decisively to precipitating the acutethrombotic complications of atheroma [3] The activated

macrophages abundant in atheroma can produce proteolyticenzymes capable of degrading the collagen that lends strengthto the plaquersquos protective fibrous cap rendering the cap thinweak and susceptible to rupture Inflammatory mediatorsregulate tissue factor expression by plaque macrophagesdemonstrating an essential link between arterial inflamma-tion and thrombosis [36]

Both innate and adaptive immunity are involved inatherosclerosis Inflammation per se can drive arterial hyper-plasia even in the absence of traditional risk factors [37]Cytokines as inflammatorymessengers provide amechanismwhereby risk factors for atherosclerosis can alter arterialbiology Inflammation regulates aspects of plaque biologythat trigger the thrombotic complications of atheroscle-rosis [38] Overall inflammatory mediators participate inall phases of atherogenesis from lesion initiation throughprogression and ultimately to the clinical complications ofthis disease The fact that all types of immune cells have beenfound in atherosclerotic plaques indicates that all immunecomponents may participate in atherogenesis All of thesefactors form the basis of the ldquoinflammatory hypothesisrdquo

3 Effects and Mechanisms of ChineseHerb Compounds in the Attenuation ofAtherosclerosis

An early description of the clinical manifestations andtreatment of atherosclerosis can be found in the classictraditional Chinese medicine book Inner Canon of YellowEmperor which was completed around 500 BC In the theoryof traditional Chinese medicine atherosclerosis is usuallyreferred to as ldquoMaiBirdquo a vascular problem that is caused byQistagnation Blood stasis andor coagulated Phlegm in whichQi stands for the energy Blood stands for the material andPhlegm stands for a kind of pathological product For overtwo thousand years atherosclerosis and its resulting heartdisease have been treated with numerous herbal remediesWhile somewhat effective these herbal remedies have notbeen well studied using evidence-based approaches or usingmodern cellular and molecular techniques Recently how-ever investigations to examine the effects andmechanisms ofsingle herbal compounds in the modulation of atherogenesishave occurred A summary of these studies is presented inthe following section wherein the compounds are discussedaccording to their site of activity

31 Chinese Herbal Compounds with Endothelial ProtectiveActivity (Table 1) The study by Lee et al demonstratedthat pretreatment of human umbilical vein endothelial cells(HUVEC) with Buddleja Officinalis (BO 1ndash10microgmL)for 18 hrs dose-dependently inhibited TNF-120572-induced adhe-sion U937 monocytic cells as well as mRNA and proteinexpressions of VCAM-1 and ICAM-1 Pretreatment withBO also blocked TNF-120572-induced reactive oxygen species(ROS) formation Nuclear factor-kappa B (NF-kappa B) isrequired for the transcription of these adhesion moleculegenes [43] Wan et al found that Panax notoginseng saponins(PNS) derived from the Chinese herb Panax notoginseng

Evidence-Based Complementary and Alternative Medicine 5

Table 1 Chinese herbal compounds with endothelial protective activity

Compound Herb Target or indicator Type of study Reference

Resveratrol Rhizoma polygonumcuspidatum cav-1 VEGF KDR In vitro [39]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO E-selectin

VCAM-1 ICAM-1 ET-1 In vivo [40]

Protocatechuicaldehyde

Salvia miltiorrhizaBunge

Caspase-3 caspase-2 Bcl-2Baxcytochrome c caspase-9granzyme B

In vitro [41]

Cryptotanshinone Salvia miltiorrhizaBunge

oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Panax notoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo bilobaextract Ginkgo biloba VCAM-1 ICAM-1 E-selectin

ROS RSTF Both [46 47]

Salvia miltiorrhiza Salvia miltiorrhizaBunge

eNOS NO NADPH oxidasesubunit Nox4 In vitro [48]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Magnolol Magnolia officinalis

IL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyteadhesion cyclin D1 MCP-1NF-kB VCAM-1

Both [50 51]

Aqueous extract ofSalvia miltiorrhiza

Salvia miltiorrhizaBunge ICAM-1 VCAM-1 GSH NF-120581B In vitro [52]

Salvianolic acid B Salvia miltiorrhizaBunge ICAM-1 E-selectin NF-120581B In vitro [53]

dose-dependently inhibited monocyte adhesion to activatedendothelium as well as the expression of TNF-120572-inducedendothelial adhesionmolecules such as ICAM-1 andVCAM-1 [45] Recent findings reported by Tian et al indicatedthat Resveratrol a compound derived from the Chineseherb Rhizoma polygonum cuspidatum downregulated theincreased expressions of vascular endothelial growth factor(VEGF) and kinase insert domain receptor (KDR or VEGFreceptor-2) [39] Results from Choi et al showed that extractfrom Cynanchum wilfordii (ECW) treatment significantlydecreased vascular inflammation through an inhibition ofcellular adhesionmolecules such as E-selectin VCAM-1 andICAM-1 as well as endothelin-1 (ET-1) expression [40]

32 Chinese Herbal Compounds That Lower Lipids and Anti-oxidation (Tables 2 and 3) Zhang et al [54] using a plasmalipid analysis approach found Celastrus orbiculatus ThunbExtract (COT) a compound derived from the Chinese herbCelastrus orbiculatus Thunb to decrease total cholesterol(TC) non-high-density lipoprotein cholesterol (non-HDL-C) triglyceride (TG) apolipoprotein B100 (apoB100) andapolipoprotein E (apoE) levels and to increase the levelof HDL cholesterol (HDL-C) Quantitative real-time PCRrevealed that COTupregulated themRNA abundance of LDLreceptor (LDL-R) scavenger receptor class B type 1 (SR-B1)

cholesterol 7120572-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [54] Choi et alreported that extract from the herb Cynanchum wilfordiitreatment in HFCD-fed rats lessened LDL cholesterol andtriglyceride levels and elevated HDL cholesterol [40] Resultsfrom Subramaniam et al indicated that the ethanolic fractionof the herb T arjuna significantly decreased TC LDL andTG levels increased HDL and lessened the number of aorticatherosclerotic lesions [57] Dinani et al demonstrated theability of the extract from the Chinese herbArtemisia aucherito significantly reduce the levels of TC LDL cholesterol andTG and to increase HDL cholesterol [58]

Li et al discovered that Farrerol an extract from theChinese herbRhododendron dauricum L significantly inhib-ited the H

2O2-induced loss of cell viability and enhanced

superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) activities in EAhy926 cells In addition Far-rerol inhibited the H

2O2-induced elevation in the levels of

intracellular malondialdehyde (MDA) and reactive oxygenspecies (ROS) [63] Chen et al reported that treatment withSalvianolic acid B (Sal B) a main compound derived from theherb Salvia miltiorrhiza Bunge suppressed ERK12 and JNKphosphorylation and attenuated the increase in prostaglandinE2 production and NADPH oxidase activity in LPS-treatedhuman aortic smoothmuscle cells (HASMCs) indicating that

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 3: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 3

Tunica media

SubendothelialspaceEndothelium

(a)

Injured endothelium

(b)

(c) (d)

Necrotic core

Fibrous cap

LDLOxidized LDLMonocyteSmooth muscle cell

MacrophageFoam cellApoptotic cell

(e)

Ruptured thrombus

B cellsT cellsMast cell

Dendritic cell

Extracellular matrixCholesterol crystals

(f)

Figure 1 A schematic drawing depicting the formation of atherosclerotic plaques (a) In the wall of a normal artery there is a very smallsubendothelial space in the intima between the endothelium and the smooth muscle cell layer in tunica media (b) Hyperlipidemia andendothelial injury lead to the infiltration of LDL particles into the subendothelial space (c) A large number of LDL particles are retainedand subsequently oxidized in the subendothelial space followed by monocyte infiltration (from lumen) and smooth muscle cell migration(from tunica media) (d) Monocytes and smooth muscle cells differentiate into macrophages which engulf LDL and turn into foam cells andare activated by oxidized LDL SMCs are also activated proliferate and transform into lipid-laden foam cells (e) Macrophage and smoothmuscle foam cells undergo apoptosis unbalanced apoptosisefferocytosis results in necrotic core formation and unresolved inflammationOther immune cell types also participate in the arterial wall inflammation (f) Erosion of the fibrous cap caused by the matrix degradingenzymes secreted by the macrophages leads to unstable plaques which eventually rupture and result in thrombus formation and adverseclinical events

4 Evidence-Based Complementary and Alternative Medicine

cells may not be a random event or the result of bursting likean overinflated balloon due to lipid overload Rather it maybe due in part to gradients of concentration of factors such asmacrophage colony-stimulating factor (M-CSF) required forsurvival of humanmonocytes [20] However some apoptoticcells may not disappear from the atherosclerotic lesions butinstead accumulate in a ldquomummifiedrdquo state [20] The elegantstudies of Ira Tabas have elaborated upon this concept ofimpaired clearance or ldquoefferocytosisrdquo of apoptotic cells inplaques which leads to unresolved inflammation [30] Theapoptotic foam cells that escape efferocytosis release theirlipid content to the extracellular space and contribute to lipidcore formation

Over the last dozen years appreciation of the role ofinflammation in atherosclerosis has burgeoned Intralesionalor extralesional inflammation may hasten atheroma evolu-tion and precipitate acute events Circulating acute-phasereactants elicited by inflammation not only may serve asa biomarker for increased risk of vascular events but alsoin some cases may contribute to their pathogenesis [31]Advances stemming from basic research have established afundamental role for inflammation in mediating all stagesof this disease from initiation through progression and ulti-mately to the thrombotic complications of atherosclerosis

The basic science of inflammatory biology applied toatherosclerosis has provided considerable insight into themechanisms underlying the recruitment of leukocytes Earlyafter the initiation of atherogenesis arterial endothelialcells begin to express on their surface selective adhesionmolecules that bind various classes of leukocytes [12] Inparticular VCAM-1 binds precisely the types of leukocytesinvolved in early atheroma the monocyte and T lymphocyteNot only does VCAM-1 expression increase on endothelialcells overlying nascent atheroma but defective VCAM-1shows interrupted lesion development [32] Once adheredto the endothelium leukocytes penetrate into the intima inresponse to chemoattractant molecules For example mono-cyte chemoattractant protein-1 (MCP-1) appears responsiblefor the direct migration of monocytes into the intima at sitesof lesion formation [33] Once resident in the arterial wall theblood-derived inflammatory cells participate in and perpetu-ate a local inflammatory response The macrophages expressscavenger receptors for modified lipoproteins permittingthem to ingest lipid and become foam cells In additionto MCP-1 macrophage colony-stimulating factor (M-CSF)contributes to the differentiation of the blood monocyte intothe macrophage foam cell [34] T cells likewise encountersignals that cause them to elaborate inflammatory cytokinessuch as tumor necrosis factor-120572 (TNF-120572) that in turn canstimulate macrophages as well as vascular endothelial cellsand SMCs [35] As this inflammatory process continues theactivated leukocytes and intrinsic arterial cells can releasefibrogenic mediators including a variety of peptide growthfactors that can promote replication of SMCs and contributeto elaboration by these cells of a dense ECM characteristic ofa more advanced atherosclerosis lesion Inflammatory pro-cesses not only promote initiation and evolution of atheromabut also contribute decisively to precipitating the acutethrombotic complications of atheroma [3] The activated

macrophages abundant in atheroma can produce proteolyticenzymes capable of degrading the collagen that lends strengthto the plaquersquos protective fibrous cap rendering the cap thinweak and susceptible to rupture Inflammatory mediatorsregulate tissue factor expression by plaque macrophagesdemonstrating an essential link between arterial inflamma-tion and thrombosis [36]

Both innate and adaptive immunity are involved inatherosclerosis Inflammation per se can drive arterial hyper-plasia even in the absence of traditional risk factors [37]Cytokines as inflammatorymessengers provide amechanismwhereby risk factors for atherosclerosis can alter arterialbiology Inflammation regulates aspects of plaque biologythat trigger the thrombotic complications of atheroscle-rosis [38] Overall inflammatory mediators participate inall phases of atherogenesis from lesion initiation throughprogression and ultimately to the clinical complications ofthis disease The fact that all types of immune cells have beenfound in atherosclerotic plaques indicates that all immunecomponents may participate in atherogenesis All of thesefactors form the basis of the ldquoinflammatory hypothesisrdquo

3 Effects and Mechanisms of ChineseHerb Compounds in the Attenuation ofAtherosclerosis

An early description of the clinical manifestations andtreatment of atherosclerosis can be found in the classictraditional Chinese medicine book Inner Canon of YellowEmperor which was completed around 500 BC In the theoryof traditional Chinese medicine atherosclerosis is usuallyreferred to as ldquoMaiBirdquo a vascular problem that is caused byQistagnation Blood stasis andor coagulated Phlegm in whichQi stands for the energy Blood stands for the material andPhlegm stands for a kind of pathological product For overtwo thousand years atherosclerosis and its resulting heartdisease have been treated with numerous herbal remediesWhile somewhat effective these herbal remedies have notbeen well studied using evidence-based approaches or usingmodern cellular and molecular techniques Recently how-ever investigations to examine the effects andmechanisms ofsingle herbal compounds in the modulation of atherogenesishave occurred A summary of these studies is presented inthe following section wherein the compounds are discussedaccording to their site of activity

31 Chinese Herbal Compounds with Endothelial ProtectiveActivity (Table 1) The study by Lee et al demonstratedthat pretreatment of human umbilical vein endothelial cells(HUVEC) with Buddleja Officinalis (BO 1ndash10microgmL)for 18 hrs dose-dependently inhibited TNF-120572-induced adhe-sion U937 monocytic cells as well as mRNA and proteinexpressions of VCAM-1 and ICAM-1 Pretreatment withBO also blocked TNF-120572-induced reactive oxygen species(ROS) formation Nuclear factor-kappa B (NF-kappa B) isrequired for the transcription of these adhesion moleculegenes [43] Wan et al found that Panax notoginseng saponins(PNS) derived from the Chinese herb Panax notoginseng

Evidence-Based Complementary and Alternative Medicine 5

Table 1 Chinese herbal compounds with endothelial protective activity

Compound Herb Target or indicator Type of study Reference

Resveratrol Rhizoma polygonumcuspidatum cav-1 VEGF KDR In vitro [39]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO E-selectin

VCAM-1 ICAM-1 ET-1 In vivo [40]

Protocatechuicaldehyde

Salvia miltiorrhizaBunge

Caspase-3 caspase-2 Bcl-2Baxcytochrome c caspase-9granzyme B

In vitro [41]

Cryptotanshinone Salvia miltiorrhizaBunge

oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Panax notoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo bilobaextract Ginkgo biloba VCAM-1 ICAM-1 E-selectin

ROS RSTF Both [46 47]

Salvia miltiorrhiza Salvia miltiorrhizaBunge

eNOS NO NADPH oxidasesubunit Nox4 In vitro [48]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Magnolol Magnolia officinalis

IL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyteadhesion cyclin D1 MCP-1NF-kB VCAM-1

Both [50 51]

Aqueous extract ofSalvia miltiorrhiza

Salvia miltiorrhizaBunge ICAM-1 VCAM-1 GSH NF-120581B In vitro [52]

Salvianolic acid B Salvia miltiorrhizaBunge ICAM-1 E-selectin NF-120581B In vitro [53]

dose-dependently inhibited monocyte adhesion to activatedendothelium as well as the expression of TNF-120572-inducedendothelial adhesionmolecules such as ICAM-1 andVCAM-1 [45] Recent findings reported by Tian et al indicatedthat Resveratrol a compound derived from the Chineseherb Rhizoma polygonum cuspidatum downregulated theincreased expressions of vascular endothelial growth factor(VEGF) and kinase insert domain receptor (KDR or VEGFreceptor-2) [39] Results from Choi et al showed that extractfrom Cynanchum wilfordii (ECW) treatment significantlydecreased vascular inflammation through an inhibition ofcellular adhesionmolecules such as E-selectin VCAM-1 andICAM-1 as well as endothelin-1 (ET-1) expression [40]

32 Chinese Herbal Compounds That Lower Lipids and Anti-oxidation (Tables 2 and 3) Zhang et al [54] using a plasmalipid analysis approach found Celastrus orbiculatus ThunbExtract (COT) a compound derived from the Chinese herbCelastrus orbiculatus Thunb to decrease total cholesterol(TC) non-high-density lipoprotein cholesterol (non-HDL-C) triglyceride (TG) apolipoprotein B100 (apoB100) andapolipoprotein E (apoE) levels and to increase the levelof HDL cholesterol (HDL-C) Quantitative real-time PCRrevealed that COTupregulated themRNA abundance of LDLreceptor (LDL-R) scavenger receptor class B type 1 (SR-B1)

cholesterol 7120572-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [54] Choi et alreported that extract from the herb Cynanchum wilfordiitreatment in HFCD-fed rats lessened LDL cholesterol andtriglyceride levels and elevated HDL cholesterol [40] Resultsfrom Subramaniam et al indicated that the ethanolic fractionof the herb T arjuna significantly decreased TC LDL andTG levels increased HDL and lessened the number of aorticatherosclerotic lesions [57] Dinani et al demonstrated theability of the extract from the Chinese herbArtemisia aucherito significantly reduce the levels of TC LDL cholesterol andTG and to increase HDL cholesterol [58]

Li et al discovered that Farrerol an extract from theChinese herbRhododendron dauricum L significantly inhib-ited the H

2O2-induced loss of cell viability and enhanced

superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) activities in EAhy926 cells In addition Far-rerol inhibited the H

2O2-induced elevation in the levels of

intracellular malondialdehyde (MDA) and reactive oxygenspecies (ROS) [63] Chen et al reported that treatment withSalvianolic acid B (Sal B) a main compound derived from theherb Salvia miltiorrhiza Bunge suppressed ERK12 and JNKphosphorylation and attenuated the increase in prostaglandinE2 production and NADPH oxidase activity in LPS-treatedhuman aortic smoothmuscle cells (HASMCs) indicating that

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 4: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

4 Evidence-Based Complementary and Alternative Medicine

cells may not be a random event or the result of bursting likean overinflated balloon due to lipid overload Rather it maybe due in part to gradients of concentration of factors such asmacrophage colony-stimulating factor (M-CSF) required forsurvival of humanmonocytes [20] However some apoptoticcells may not disappear from the atherosclerotic lesions butinstead accumulate in a ldquomummifiedrdquo state [20] The elegantstudies of Ira Tabas have elaborated upon this concept ofimpaired clearance or ldquoefferocytosisrdquo of apoptotic cells inplaques which leads to unresolved inflammation [30] Theapoptotic foam cells that escape efferocytosis release theirlipid content to the extracellular space and contribute to lipidcore formation

Over the last dozen years appreciation of the role ofinflammation in atherosclerosis has burgeoned Intralesionalor extralesional inflammation may hasten atheroma evolu-tion and precipitate acute events Circulating acute-phasereactants elicited by inflammation not only may serve asa biomarker for increased risk of vascular events but alsoin some cases may contribute to their pathogenesis [31]Advances stemming from basic research have established afundamental role for inflammation in mediating all stagesof this disease from initiation through progression and ulti-mately to the thrombotic complications of atherosclerosis

The basic science of inflammatory biology applied toatherosclerosis has provided considerable insight into themechanisms underlying the recruitment of leukocytes Earlyafter the initiation of atherogenesis arterial endothelialcells begin to express on their surface selective adhesionmolecules that bind various classes of leukocytes [12] Inparticular VCAM-1 binds precisely the types of leukocytesinvolved in early atheroma the monocyte and T lymphocyteNot only does VCAM-1 expression increase on endothelialcells overlying nascent atheroma but defective VCAM-1shows interrupted lesion development [32] Once adheredto the endothelium leukocytes penetrate into the intima inresponse to chemoattractant molecules For example mono-cyte chemoattractant protein-1 (MCP-1) appears responsiblefor the direct migration of monocytes into the intima at sitesof lesion formation [33] Once resident in the arterial wall theblood-derived inflammatory cells participate in and perpetu-ate a local inflammatory response The macrophages expressscavenger receptors for modified lipoproteins permittingthem to ingest lipid and become foam cells In additionto MCP-1 macrophage colony-stimulating factor (M-CSF)contributes to the differentiation of the blood monocyte intothe macrophage foam cell [34] T cells likewise encountersignals that cause them to elaborate inflammatory cytokinessuch as tumor necrosis factor-120572 (TNF-120572) that in turn canstimulate macrophages as well as vascular endothelial cellsand SMCs [35] As this inflammatory process continues theactivated leukocytes and intrinsic arterial cells can releasefibrogenic mediators including a variety of peptide growthfactors that can promote replication of SMCs and contributeto elaboration by these cells of a dense ECM characteristic ofa more advanced atherosclerosis lesion Inflammatory pro-cesses not only promote initiation and evolution of atheromabut also contribute decisively to precipitating the acutethrombotic complications of atheroma [3] The activated

macrophages abundant in atheroma can produce proteolyticenzymes capable of degrading the collagen that lends strengthto the plaquersquos protective fibrous cap rendering the cap thinweak and susceptible to rupture Inflammatory mediatorsregulate tissue factor expression by plaque macrophagesdemonstrating an essential link between arterial inflamma-tion and thrombosis [36]

Both innate and adaptive immunity are involved inatherosclerosis Inflammation per se can drive arterial hyper-plasia even in the absence of traditional risk factors [37]Cytokines as inflammatorymessengers provide amechanismwhereby risk factors for atherosclerosis can alter arterialbiology Inflammation regulates aspects of plaque biologythat trigger the thrombotic complications of atheroscle-rosis [38] Overall inflammatory mediators participate inall phases of atherogenesis from lesion initiation throughprogression and ultimately to the clinical complications ofthis disease The fact that all types of immune cells have beenfound in atherosclerotic plaques indicates that all immunecomponents may participate in atherogenesis All of thesefactors form the basis of the ldquoinflammatory hypothesisrdquo

3 Effects and Mechanisms of ChineseHerb Compounds in the Attenuation ofAtherosclerosis

An early description of the clinical manifestations andtreatment of atherosclerosis can be found in the classictraditional Chinese medicine book Inner Canon of YellowEmperor which was completed around 500 BC In the theoryof traditional Chinese medicine atherosclerosis is usuallyreferred to as ldquoMaiBirdquo a vascular problem that is caused byQistagnation Blood stasis andor coagulated Phlegm in whichQi stands for the energy Blood stands for the material andPhlegm stands for a kind of pathological product For overtwo thousand years atherosclerosis and its resulting heartdisease have been treated with numerous herbal remediesWhile somewhat effective these herbal remedies have notbeen well studied using evidence-based approaches or usingmodern cellular and molecular techniques Recently how-ever investigations to examine the effects andmechanisms ofsingle herbal compounds in the modulation of atherogenesishave occurred A summary of these studies is presented inthe following section wherein the compounds are discussedaccording to their site of activity

31 Chinese Herbal Compounds with Endothelial ProtectiveActivity (Table 1) The study by Lee et al demonstratedthat pretreatment of human umbilical vein endothelial cells(HUVEC) with Buddleja Officinalis (BO 1ndash10microgmL)for 18 hrs dose-dependently inhibited TNF-120572-induced adhe-sion U937 monocytic cells as well as mRNA and proteinexpressions of VCAM-1 and ICAM-1 Pretreatment withBO also blocked TNF-120572-induced reactive oxygen species(ROS) formation Nuclear factor-kappa B (NF-kappa B) isrequired for the transcription of these adhesion moleculegenes [43] Wan et al found that Panax notoginseng saponins(PNS) derived from the Chinese herb Panax notoginseng

Evidence-Based Complementary and Alternative Medicine 5

Table 1 Chinese herbal compounds with endothelial protective activity

Compound Herb Target or indicator Type of study Reference

Resveratrol Rhizoma polygonumcuspidatum cav-1 VEGF KDR In vitro [39]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO E-selectin

VCAM-1 ICAM-1 ET-1 In vivo [40]

Protocatechuicaldehyde

Salvia miltiorrhizaBunge

Caspase-3 caspase-2 Bcl-2Baxcytochrome c caspase-9granzyme B

In vitro [41]

Cryptotanshinone Salvia miltiorrhizaBunge

oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Panax notoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo bilobaextract Ginkgo biloba VCAM-1 ICAM-1 E-selectin

ROS RSTF Both [46 47]

Salvia miltiorrhiza Salvia miltiorrhizaBunge

eNOS NO NADPH oxidasesubunit Nox4 In vitro [48]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Magnolol Magnolia officinalis

IL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyteadhesion cyclin D1 MCP-1NF-kB VCAM-1

Both [50 51]

Aqueous extract ofSalvia miltiorrhiza

Salvia miltiorrhizaBunge ICAM-1 VCAM-1 GSH NF-120581B In vitro [52]

Salvianolic acid B Salvia miltiorrhizaBunge ICAM-1 E-selectin NF-120581B In vitro [53]

dose-dependently inhibited monocyte adhesion to activatedendothelium as well as the expression of TNF-120572-inducedendothelial adhesionmolecules such as ICAM-1 andVCAM-1 [45] Recent findings reported by Tian et al indicatedthat Resveratrol a compound derived from the Chineseherb Rhizoma polygonum cuspidatum downregulated theincreased expressions of vascular endothelial growth factor(VEGF) and kinase insert domain receptor (KDR or VEGFreceptor-2) [39] Results from Choi et al showed that extractfrom Cynanchum wilfordii (ECW) treatment significantlydecreased vascular inflammation through an inhibition ofcellular adhesionmolecules such as E-selectin VCAM-1 andICAM-1 as well as endothelin-1 (ET-1) expression [40]

32 Chinese Herbal Compounds That Lower Lipids and Anti-oxidation (Tables 2 and 3) Zhang et al [54] using a plasmalipid analysis approach found Celastrus orbiculatus ThunbExtract (COT) a compound derived from the Chinese herbCelastrus orbiculatus Thunb to decrease total cholesterol(TC) non-high-density lipoprotein cholesterol (non-HDL-C) triglyceride (TG) apolipoprotein B100 (apoB100) andapolipoprotein E (apoE) levels and to increase the levelof HDL cholesterol (HDL-C) Quantitative real-time PCRrevealed that COTupregulated themRNA abundance of LDLreceptor (LDL-R) scavenger receptor class B type 1 (SR-B1)

cholesterol 7120572-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [54] Choi et alreported that extract from the herb Cynanchum wilfordiitreatment in HFCD-fed rats lessened LDL cholesterol andtriglyceride levels and elevated HDL cholesterol [40] Resultsfrom Subramaniam et al indicated that the ethanolic fractionof the herb T arjuna significantly decreased TC LDL andTG levels increased HDL and lessened the number of aorticatherosclerotic lesions [57] Dinani et al demonstrated theability of the extract from the Chinese herbArtemisia aucherito significantly reduce the levels of TC LDL cholesterol andTG and to increase HDL cholesterol [58]

Li et al discovered that Farrerol an extract from theChinese herbRhododendron dauricum L significantly inhib-ited the H

2O2-induced loss of cell viability and enhanced

superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) activities in EAhy926 cells In addition Far-rerol inhibited the H

2O2-induced elevation in the levels of

intracellular malondialdehyde (MDA) and reactive oxygenspecies (ROS) [63] Chen et al reported that treatment withSalvianolic acid B (Sal B) a main compound derived from theherb Salvia miltiorrhiza Bunge suppressed ERK12 and JNKphosphorylation and attenuated the increase in prostaglandinE2 production and NADPH oxidase activity in LPS-treatedhuman aortic smoothmuscle cells (HASMCs) indicating that

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 5: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 5

Table 1 Chinese herbal compounds with endothelial protective activity

Compound Herb Target or indicator Type of study Reference

Resveratrol Rhizoma polygonumcuspidatum cav-1 VEGF KDR In vitro [39]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO E-selectin

VCAM-1 ICAM-1 ET-1 In vivo [40]

Protocatechuicaldehyde

Salvia miltiorrhizaBunge

Caspase-3 caspase-2 Bcl-2Baxcytochrome c caspase-9granzyme B

In vitro [41]

Cryptotanshinone Salvia miltiorrhizaBunge

oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Panax notoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo bilobaextract Ginkgo biloba VCAM-1 ICAM-1 E-selectin

ROS RSTF Both [46 47]

Salvia miltiorrhiza Salvia miltiorrhizaBunge

eNOS NO NADPH oxidasesubunit Nox4 In vitro [48]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Magnolol Magnolia officinalis

IL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyteadhesion cyclin D1 MCP-1NF-kB VCAM-1

Both [50 51]

Aqueous extract ofSalvia miltiorrhiza

Salvia miltiorrhizaBunge ICAM-1 VCAM-1 GSH NF-120581B In vitro [52]

Salvianolic acid B Salvia miltiorrhizaBunge ICAM-1 E-selectin NF-120581B In vitro [53]

dose-dependently inhibited monocyte adhesion to activatedendothelium as well as the expression of TNF-120572-inducedendothelial adhesionmolecules such as ICAM-1 andVCAM-1 [45] Recent findings reported by Tian et al indicatedthat Resveratrol a compound derived from the Chineseherb Rhizoma polygonum cuspidatum downregulated theincreased expressions of vascular endothelial growth factor(VEGF) and kinase insert domain receptor (KDR or VEGFreceptor-2) [39] Results from Choi et al showed that extractfrom Cynanchum wilfordii (ECW) treatment significantlydecreased vascular inflammation through an inhibition ofcellular adhesionmolecules such as E-selectin VCAM-1 andICAM-1 as well as endothelin-1 (ET-1) expression [40]

32 Chinese Herbal Compounds That Lower Lipids and Anti-oxidation (Tables 2 and 3) Zhang et al [54] using a plasmalipid analysis approach found Celastrus orbiculatus ThunbExtract (COT) a compound derived from the Chinese herbCelastrus orbiculatus Thunb to decrease total cholesterol(TC) non-high-density lipoprotein cholesterol (non-HDL-C) triglyceride (TG) apolipoprotein B100 (apoB100) andapolipoprotein E (apoE) levels and to increase the levelof HDL cholesterol (HDL-C) Quantitative real-time PCRrevealed that COTupregulated themRNA abundance of LDLreceptor (LDL-R) scavenger receptor class B type 1 (SR-B1)

cholesterol 7120572-hydroxylase A1 (CYP7A1) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [54] Choi et alreported that extract from the herb Cynanchum wilfordiitreatment in HFCD-fed rats lessened LDL cholesterol andtriglyceride levels and elevated HDL cholesterol [40] Resultsfrom Subramaniam et al indicated that the ethanolic fractionof the herb T arjuna significantly decreased TC LDL andTG levels increased HDL and lessened the number of aorticatherosclerotic lesions [57] Dinani et al demonstrated theability of the extract from the Chinese herbArtemisia aucherito significantly reduce the levels of TC LDL cholesterol andTG and to increase HDL cholesterol [58]

Li et al discovered that Farrerol an extract from theChinese herbRhododendron dauricum L significantly inhib-ited the H

2O2-induced loss of cell viability and enhanced

superoxide dismutase (SOD) and glutathione peroxidase(GSH-Px) activities in EAhy926 cells In addition Far-rerol inhibited the H

2O2-induced elevation in the levels of

intracellular malondialdehyde (MDA) and reactive oxygenspecies (ROS) [63] Chen et al reported that treatment withSalvianolic acid B (Sal B) a main compound derived from theherb Salvia miltiorrhiza Bunge suppressed ERK12 and JNKphosphorylation and attenuated the increase in prostaglandinE2 production and NADPH oxidase activity in LPS-treatedhuman aortic smoothmuscle cells (HASMCs) indicating that

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 6: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

6 Evidence-Based Complementary and Alternative Medicine

Table 2 Chinese herbal compounds that lower lipids

Compound Herb Target or indicator Type of study Reference

CelastrusorbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100apoE HDL LDL receptor SR-B1CYP7A1 HMGCR CRP MDA

In vivo [54]

Salvianolic acid B Salvia MiltiorrhizaBunge mLDL CD36 In vitro [55]

Cynanchumwilfordii Cynanchum wilfordii LDL HDL NO Akt In vivo [56]

Ethanolic fractionof T arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Artemisia aucheri Artemisia aucheriTotal cholesterol LDLcholesterol triglycerides HDLcholesterol

In vivo [58]

Tribulus terrestrisextract Tribulus terrestris TC HDL LDL TG In vivo [44]

Ginsenosides Panax spp PPARs total cholesteroltriglyceride In vivo [59]

Ocimum basilicum Ocimum basilicumTotal cholesterol triglyceridesLDL-cholesterolHDL-cholesterol

In vivo [60]

Sal B has antioxidant properties [71] Jia et al showed thatTanshinone IIA (TSN IIA) another main compound derivedfrom the Chinese herb Salvia Miltiorrhiza Bunge markedlyinhibited the elevation of ROS evoked by H

2O2 Real time

RT-PCR and Western blotting analysis demonstrated theability of TSN IIA to significantly decrease theH

2O2-induced

expression of proapoptotic proteins Bax and caspase-3 and tosignificantly increase the expression of antiapoptotic proteinBcl-2 in EAhy926 cells [64]

Results fromXu et al showed that the Lectin-like oxidizedLDL (oxLDL) receptor-1 (LOX-1) a novel scavenger receptorhighly expressed in human and experimental atheroscleroticlesions is responsible for the uptake of oxLDL in vascularcells oxLDL induced LOX-1 expression at the mRNA andprotein levels which was abrogated by the addition of Tan-shinone IIA or a widely used inhibitor of NF-120581B suggestingthe involvement of NF-120581B [65] Hung et al described thata low dose (0015mgmL) of S miltiorrhiza aqueous extract(SMAE) derived from the Chinese herb Salvia miltiorrhizaBunge significantly inhibited the growth of a rat smoothmuscle cell line (A10) under Hcy stimulation and the intra-cellular ROS concentration decreased after SMAE treatmentin terms of reducing p47 (phox) translocation and increasingcatalase activity The signaling profile suggests that SMAEinhibited Hcy-induced A10 cell growth via the PKCMAPK-dependent pathway [68]

33 Chinese Herbal Compounds That Suppress MonocyteMigration and Activation (Table 4) Within plaque forma-tion activated endothelial cells increase the expression ofadhesion molecules and inflammatory genes and circulatingmonocytes migrate into subendothelial space and differen-tiate into macrophages In support of this concept Chenet al found that extract from Ginkgo biloba a Chineseherb with antioxidant activity could significantly suppress

inflammatory cytokine-stimulated endothelial adhesivenessto human monocytic cells by attenuating intracellular ROSformation redox-sensitive transcription factor activationand VCAM-1 as well as ICAM-1 expression in human aorticendothelial cells [46] Wan et al found that Panax notogin-seng saponins (PNS) dose-dependently inhibited monocyteadhesion on activated endothelium as well as the expressionof TNF-120572-induced endothelial adhesion molecules such asICAM-1 and VCAM-1 [45] According to the report byPark Prunella vulgaris ethanol extract inhibited adhesionof monocytemacrophage-like THP-1 cells to the activatedHASMCs [91] The role of Curcumin derived from theChinese herb Curcuma longa was shown by Wang et al tohave a sonodynamic effect on THP-1-derived macrophagesand therefore to be a promising treatment for atherosclerosis[92] Finally Duan et al identifiedPhyllanthus emblica extractas being able to prevent ECV-304 cells from adhering tomonocytes [79]

34 Chinese Herbal Compounds That Suppress VSMC Migra-tion and Proliferation (Table 5) Several lines of evidenceexist to indicate the effectiveness of Chinese herbs onVSMC migration and proliferation Moon et al observedthat Protocatechuic aldehyde (PCA) a compound derivedfrom theChinese herb Salviamiltiorrhiza Bunge significantlyattenuated PDGF-induced VSMC proliferation and migra-tion at a pharmacologically relevant concentration (100 120583M)On a molecular level they observed downregulation of thephosphatidylinositol 3-kinase (PI3 K)Akt and the mitogen-activated protein kinase (MAPK) pathways both of whichare known to regulate key enzymes associated withmigrationand proliferation Moreover they found that PCA arrestedthe S-phase of the VSMC cell cycle and suppressed cyclinD2 expression [93] Results from Kim et al indicatedthat Corynoxeine derived from the Chinese herb Hook of

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 7: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 7

Table 3 Chinese herbal compounds with antioxidation activity

Compound Herb Target or indicator Type of study ReferenceArisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Andrographolidederivatives Andrographolide VLDL-C LDL-C HDL-C superoxide

anions hydroxyl radicals In vivo [62]

Farrerol Rhododendron dauricum L(ManShanHong) SOD GSH-Px caspase-3 p38 MAPK Bcl-2 In vitro [63]

Celastrus orbiculatusThunb Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoE HDLLDL receptor SR-B1 CYP7A1 HMGCRCRP MDA

In vivo [54]

Tanshinone IIA Salvia miltiorrhiza Bunge

ROS BaxBcl-2 caspase-3 LOX-1 NF-120581BoxLDL monocyte adhesion VSMCmigration and proliferation macrophagecholesterol accumulation TNF-120572 TGF-1205731platelet aggregation GPx

Both [64ndash67]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1 monocyteadhesion In vitro [42]

Ethanolic fraction ofT arjuna Terminalia arjuna LDL TG VLDL HDL In vivo [57]

Salvia miltiorrhizaaqueous extract Salvia miltiorrhiza Bunge Hcy ROS PKCMAPK In vivo [68]

Chlorophytumborivilianum rootextract

Chlorophytum borivilianum LDL oxidation lipid hydroperoxidesthiobarbituric acid In vitro [69]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Salvianolic acid B Salvia miltiorrhiza BungeoxLDL ROS COX ERK12 JNK MAPKprostaglandin E2 NADPH oxidase MMP-2MMP-9

Both [70ndash73]

Caffeoylquinic acids(CQs) Chwinamul ROS Both [74]

Epimedium(Berberidaceae) Epimedium spp ROS Both [75]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROS RSTF Both [46]Salvia miltiorrhiza Salvia miltiorrhiza Bunge eNOS NO NADPH oxidase subunit Nox4 In vitro [48]Scutellaria baicalensisGeorgi flavonoids Scutellaria baicalensis Georgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Ethanol extract ofGlossogyne tenuifolia Glossogyne tenuifolia oxLDL ROS In vitro [80]

Ocimum basilicum Ocimum basilicum total cholesterol triglycerides LDL HDL In vivo [60]Paeonol Paeonia lactiflora Pallas ICAM-1 NF-120581B p65 translocation ERK p38 In vitro [81]Water extracts ofAchyroclinesatureoides

Achyrocline satureoides LDL oxidation In vitro [82]

Alaternin Cassia tora NO Peroxynitrite In vitro [83]Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge Hcy In vitro [84]

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 8: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

8 Evidence-Based Complementary and Alternative Medicine

Table 3 Continued

Compound Herb Target or indicator Type of study ReferenceGypenosidesSaponins Gynostemma pentaphyllum mitochondrial enzyme In vitro [85]

baicalein baicalin andwogonin Scutellaria baicalensis VSMC proliferation In vitro [86]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foam cells In vivo [87]Trilinolein Panax pseudoginseng OFR In vitro [88]

Celastrol Tripterygium wilfordiiHook F oxLDL LOX-1 ROS iNOS NO TNF-aIL-6 In vivo [89]

Phenolic Rye (Secalecereale L) Ferulic acid oxLDL In vitro [90]

Table 4 Chinese herbal compounds that suppress monocyte migration and activation

Compound Herb Target or indicator Type of study ReferencePrunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin

ROS p38 MAPK ERK In vitro [91]

Curcumin Curcuma longa Macrophage morphologicalchanges In vitro [92]

Panaxnotoginseng Panax notoginsengsaponins ICAM-1 and VCAM-1 In vivo [45]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectinROS RSTF Both [46]

Phyllanthus emblicaextract Phyllanthus emblica oxLDL MDA In vitro [79]

Table 5 Chinese herbal compounds that suppress VSMC migration and proliferation

Compound Herb Target or indicator Type of study ReferenceProtocatechuicaldehyde

Salvia miltiorrhizaBunge PI3KAkt MAPK cyclin D2 In vitro [93]

Gleditsia sinensisthorn extract

Gleditsia sinensisthorns

MMP-9 p21WAF1 cyclinB1Cdc2 and Cdc25c ERK12 p38MAPK JNK NF-120581B AP-1

In vitro [94]

Corynoxeine Hook of Uncariarhynchophylla

DNA synthesis of VSMCsERK12 In vivo [95]

Phyllanthus emblicaextract Phyllanthus emblica ox-LDL MDA In vitro [79]

Berberine Coptis chinensis MAPK12 ERK Egr-1 PDGFc-Fos Cyclin D1 In vitro [96]

Nucifera leaf extract Nelumbo nuciferaGAERTN

JNK MAPK FAKPI3-kinasesmall G protein In vitro [97]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L triglyceride LDL foam cell

formation VSMC migration In vivo [98]

Panax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone Artemisia scoparia monocyte adhesion lipid ladenfoam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L TC LDL-C foam cell formation

VSMC migration In vivo [98]

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 9: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 9

Table 6 Chinese herbal compounds that suppress foam cell formation

Compound Herb Target or indicator Type of study ReferencePanax notoginsengsaponins Panax notoginseng integrin FAK NF-120581B In vivo [99]

Astragaluspolysaccharide

Astragalusmembranaceus ABCA1 NF-120581B In vitro [100]

Scoparone (67-dimethoxycoumarin) Artemisia scoparia monocyte adhesion

lipid laden foam cells In vivo [87]

Hibiscus sabdariffaExtract Hibiscus sabdariffa L

TC LDL-C foam cellformation VSMCmigration

In vivo [98]

Uncaria rhynchophylla significantly inhibited the PDGF-BB-induced DNA synthesis of VSMCs in a concentration-dependent manner without causing any cytotoxicity Prein-cubation of VSMCs with corynoxeine significantly inhibitedPDGF-BB-induced extracellular signal-regulated kinase 12(ERK12) activation [95] Liang et al showed that Berber-ine a compound from the Chinese herb Coptis chinensisinhibited serum-stimulated rat aortic VSMC growth in aconcentration-dependent manner Berberine blocked injury-induced VSMC regrowth by inactivation of the ERKEgr-1 signaling pathway thereby preventing the early signalinginduced by injury in vitro [96]

35 Chinese Herb Compounds That Suppress Foam Cell For-mation (Table 6) In the studies reported by Yuan et al theformation of foam cells was inhibited by Panax notoginsengsaponins (PNS) via its ability to inhibit the phosphorylationof FAK on threonine 397 and the translocation of NF-120581BWang et al discovered that TNF-120572 could enhance the activityof NF-kappa B in the foam cells and this effect could beattenuated by Astragalus polysaccharide (APS) a compoundderived from the Chinese herb Astragalus membranaceus[99] In a study by Chen et al large numbers of monocyteswere found adherent to the luminal surface and a markedlythickened intima filled with many lipid laden foam cellswas apparent However when treated with Scoparone acompoundderived from theChinese herbArtemisia scopariaatherosclerosis was less advanced and the plasma cholesterolwas lower [87] Interestingly Chen et al reported that uponhistopathological examination Hibiscus sabdariffa Extract(HSE) was noted to reduce foam cell formation and inhibitsmooth muscle cell migration and calcification in the bloodvessel of rabbits These results clearly indicate that Chineseherb-derived extracts can be used to lower serum lipids andproduce antiatherosclerotic activity [98]

36 Anti-Inflammatory Chinese Herb Compounds (Table 7)Intralesional or extralesional inflammation may hastenatheroma evolution and precipitate acute adverse eventsHence herb-associated treatment targeting inflammation isbeneficial From the findings of Jia et al real time RT-PCR and Western blotting analysis revealed that TanshinoneIIA (TSN IIA) significantly decreased the expressions ofthe proapoptotic proteins Bax and caspase-3 significantlyincreased the expression of antiapoptotic protein Bcl-2 and

resulted in the reduction of the BaxBcl-2 ratio in EAhy926cells induced by H

2O2[64] Li et al reported that Farrerol

inhibitedH2O2-induced elevation in the levels of intracellular

malondialdehyde andROS as well as cell apoptosis [63] Xinget al found that LPS (15 120583gmL) stimulation for 30 hr resultedin significant HUVEC apoptosis as detected by Hoechst33258 staining and Annexin V analysis and that Protocat-echuic aldehyde (PCA 025ndash10mmolL 12 h) inhibited theapoptosis in a dose-dependent manner [41]

Recently the research ofNapagoda et al indicated that theethnopharmacological use of Plectranthus zeylanicus extractconstituted an anti-inflammatory remedy [101] Zhang etal found that Celastrus orbiculatus Thunb (COT) loweredthe levels of C-reactive protein (CRP) interleukin-6 (IL-6) and TNF-120572 in plasma [54] Wang et al discovered thatArtemisinin a compound derived from the Chinese herbArtemisia annua inhibited the secretion and mRNA levelsof TNF-120572 interleukin (IL)-1120573 and IL-6 in a dose-dependentmanner in THP-1 human monocytes They also found thatthe NF-120581B pathway may be involved in a decreased cytokinerelease [107] Chen and Cheng reported that the extract fromChinese herb Feverfew effectively reduced LPS-mediatedTNF-120572 and CCL2 (MCP-1) release by THP-1 cells [109]

4 Summary and Perspective

Herein we have reviewed most of the Chinese herbal com-pounds recently reported to have antiatherogenic propertieseither in vitro or in vivo Chinese herbal medicine has thepotential to provide amajor public health benefit by reducingmorbidity andmortality secondary to cardiovascular diseaseRecent experimental prevention and treatment studies usingChinese medicine clearly demonstrate the benefits of low-ering LDL retention and LDL oxidant protecting endothe-lium inhibiting monocytemacrophageVSMC proliferationand migration and preventing foam cell formation as wellas the accompanying inflammation While the promise ofChinese herb-derived compounds as effective therapies foratherosclerotic cardiovascular diseases has been indicatedin the literature the published studies have severe limi-tations and apparently more research is required Firstlymost of the clinical studies are of limited value becauseof the small sample size andor incomplete data and mostexperimental studies have focused mainly on single com-pounds extracted from Chinese herbs Studies of Chinese

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 10: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

10 Evidence-Based Complementary and Alternative Medicine

Table 7 Anti-inflammatory Chinese herbal compounds

Compound Herb Target or indicator Type of study ReferencePlectranthuszeylanicus extracts

Plectranthus zeylanicusBenth 5-LO In vitro [101]

Arisaema tortuosumtuber extract Arisaema tortuosum Schott 120573-Glucuronidase FRAP In vitro [61]

Prunella vulgarisethanol extract Prunella vulgaris VCAM-1 ICAM-1 E-selectin ROS

p38 MAPK ERK In vitro [91]

Celastrus orbiculatusThunb

Celastrus orbiculatusThunb

TC non-HDL TG apoB100 apoEHDL LDL receptor SR-B1 CYP7A1HMGCR CRP MDA

In vivo [54]

23541015840-Tetrahydroxystilbene-2-O-120573-D-glucoside(TSG)

Polygonum multiflorum HSP 70 lipocortin 1 Apo A-Icalreticulin vimentin In vivo [102]

Salvianolic acid B Salvia miltiorrhiza Bunge

JAK2 (Tyr 10071008) STAT1 (Tyr701and Ser727) CXC chemokinesrsquo IP-10Mig I-TAC monocyte adhesionPIAS1 SOCS1

In vitro [103]

Cynanchum wilfordii Cynanchum wilfordii LDL HDL NO E-selectin VCAM-1ICAM-1 ET-1 In vivo [40]

Panax notoginsengextract Panax notoginseng TNF-120572 IL-6 TGF-120573 IL-1120573 In vivo [104]

Cryptotanshinone Salvia miltiorrhiza Bunge oxLDL NO ICAM-1 VCAM-1monocyte adhesion In vitro [42]

Salvianolic acid B Salvia miltiorrhiza Bunge

CD40 CD86 CD1a HLA-DR IL-12IL-10 TNF-120572 TLR4 PPAR120574p38-MAPK PAI-1 JNK NF-120581B COXERK12 prostaglandin E2 NADPHoxidase MMP-2 MMP-9 oxLDLICAM-1 E-selectin

Both [53 71 72105 106]

Tanshinone IIA Salvia miltiorrhiza Bunge

oxLDL monocyte adhesion VSMCmigration and proliferationmacrophage cholesterol accumulationTNF-120572 TGF-1205731 platelet aggregationGPx

Both [66 67]

Aqueous extract ofBuddleja officinalis Buddleja officinalis VCAM-1 ICAM-1 ROS NF-120581B In vitro [43]

Artemisinin Artemisia annua TNF-120572 IL-1szlig IL-6 NF-120581B IKK120572szligI120581B120572 In vitro [107]

Evodiamine Evodia rutaecarpa COX-2 iNOS prostaglandin E2HIF-1a Akt p70S6K 4E-BP In vitro [108]

Panax notoginseng Panax notoginsengsaponins ICAM-1 VCAM-1 In vivo [45]

Goji Lycium barbarum and Lchinense SOD MDA JNK Both [76]

Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 E-selectin ROSRSTF Both [46]

Scutellaria baicalensisGeorgi flavonoids

Scutellaria baicalensisGeorgi SOD Both [77]

Emodin Rheum rhabarbarum ApoE PPAR-120574 GM-CSF MMP-9 In vivo [78]

Bisacurone Curcuma longa Linne(Zingiberaceae) VCAM-1 NF-120581B p65 Akt PKC In vitro [49]

Feverfew extract Tanacetum parthenium TNF-120572 CCL2 In vitro [109]

Magnolol Magnolia officinalisIL-6 STAT3 Tyr705 and Ser727ICAM-1 IREs monocyte adhesioncyclin D1 MCP-1

In vitro [50]

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 11: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 11

Table 7 Continued

Compound Herb Target or indicator Type of study Reference

Paeonol Paeonia lactiflora Pallas ICAM-1 NF-kB p65 translocationERK p38 In vitro [81]

Aqueous extract ofSalvia miltiorrhiza Salvia miltiorrhiza Bunge ICAM-1 VCAM-1 GSH NF-kB In vitro [52]

Magnolol Magnolia officinalis MCP-1 NF-120581B VCAM-1 In vivo [51]Ginkgo biloba extract Ginkgo biloba VCAM-1 ICAM-1 In vitro [47]

Scoparone Artemisia scoparia monocyte adhesion lipid laden foamcells In vivo [87]

Celastrol Tripterygium wilfordiiHook F

oxLDL LOX-1 ROS iNOS NOTNF-120572 IL-6 In vivo [89]

decoctions or formulations are scarce although decoctionand formulations are the main forms of therapy in traditionalChinese medicine practice Capitalization of the interactionsbetween the different components and herbs is the essenceof traditional Chinese medicine whereby herbs are combinedto attenuate toxicity as well as to enhance efficacy Secondlylike other therapies Chinese herbs and the compoundsderived from them are expected to have side effects Howeverpublished in vivo studies seldom mention whether adverseeffects occurred In future studies including animal studiesand clinical studies systemic and organ-specific side effectsof Chinese herb medicine should be carefully examinedThirdly in modern medical practice it is unlikely thatChinese herbal medicine will be used as a sole treatmentfor cardiovascular disease instead they will more likely beused in combination with other proven drugs Therefore theherb-drug interaction should be carefully evaluated in futurestudies where Chinese herbs or compounds are used in addi-tion to traditional proven therapies Fourth atherosclerosisis a multiple-staged andmultifaceted disease most publishedstudies are focused on examining the effects of Chinese herbmedicine on one or only a few aspects of the disease In futurestudies a more systemic evaluation of the effects of Chineseherbal medicine on all aspects of atherosclerosis should beperformed including lipoprotein metabolism endothelialinjury systemic and arterial local inflammation as well as cellapoptosis and efferocytosis dynamicsbalance in the plaques

Abbreviations

5-LO 5-LipoxygenaseABCA1 ATP-binding cassette transporter

A1AP-1 Activator protein-1ApoB100 Apolipoprotein B100ApoE Apolipoprotein ECav-1 Caveolin-1CDC6 Cell division cycle 6COX CyclooxygenaseCRP C-Reactive proteinCYP7A1 Cholesterol 7120572-hydroxylase A1Egr-1 Early growth response protein 1ERK Extracellular-signal-regulated

kinase

E-selectin Endothelial cell selectinET-1 Endothelin-1FRAP Ferric reducing antioxidant powerGM-CSF Granulocyte-macrophage

colony-stimulating factorGPx Glutathione peroxidaseGSH Intracellular glutathioneHcy HomocysteineHGL High density lipoproteinHIF-1120572 Hypoxia-inducible factor 1alphaHMGCR 3-Hydroxy-3-methyl-glutaryl-CoA

reductaseICAM-1 Intercellular cell adhesion

molecule-1IL InterleukiniNOS Inducible nitric oxide synthaseIREs IL-6 response elementsJNK c-Jun NH2-terminal kinaseKDR or VEGFreceptor-2

Kinase insert domain receptor

LDL Low density lipoproteinLOX-1 Oxidized low density lipoprotein

receptor-1MAPK p38 mitogen-activated protein

kinaseMCP-1 Monocyte chemotactic protein-1MDA MalondialdehydemLDL Modified low density lipoproteinMMP Matrix metalloproteinaseNF-120581B Nuclear factor kappa BNO Nitric oxidenon-HDL Non-high-density lipoproteinOFR Oxygen-derived free radicalsoxLDL Oxidized low-density lipoproteinPAI-1 Plasminogen activator inhibitor

type 1PDGF Platelet-derived growth factorPI3K Phosphatidylinositol 3-kinasePPARs Peroxisome proliferator-activated

receptorsROS Reactive oxygen speciesRSTF Redox-sensitive transcription

factorSOD Superoxide dismutase

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 12: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

12 Evidence-Based Complementary and Alternative Medicine

SR-B1 Scavenger receptor class B type 1STAT3 Signal transducer and activator of

transcription protein 3TC Total cholesterolTG TriglyceridesTNF-120572 Tumor necrosis factor-120572VCAM-1 Vascular cell adhesion molecule-1VEGF Vascular endothelial growth factorVLDL Very low density lipoproteinVSMC Vascular smooth muscle cell

Conflict of Interests

The authors declare that they have no conflict of interestsregarding the publication of this paper

Acknowledgment

This work was supported by Grants from the NationalInstitute of Health nos R21AT006767 and R01HL116626 (toDaping Fan)

References

[1] W Insull Jr ldquoThe pathology of atherosclerosis plaque develop-ment and plaque responses tomedical treatmentrdquoTheAmericanJournal of Medicine vol 122 no 1 pp S3ndashS14 2009

[2] M B Furie and R N Mitchell ldquoPlaque attack one hundredyears of atherosclerosis in the American Journal of PathologyrdquoTheAmerican Journal of Pathology vol 180 no 6 pp 2184ndash21872012

[3] P Libby P M Ridker and A Maseri ldquoInflammation and ather-osclerosisrdquo Circulation vol 105 no 9 pp 1135ndash1143 2002

[4] N Foin P Evans and R Krams ldquoAtherosclerosis cell biologyand lipoproteinsmdashnew developments in imaging of inflamma-tion of the vulnerable plaquerdquo Current Opinion in Lipidologyvol 19 no 1 pp 98ndash100 2008

[5] A Tavridou and V G Manolopoulos ldquoNovel molecules tar-geting dyslipidemia and atherosclerosisrdquo Current MedicinalChemistry vol 15 no 8 pp 792ndash802 2008

[6] D Steinberg ldquoThematic review series the pathogenesis ofatherosclerosis an interpretive history of the cholesterol con-troversy part III mechanistically defining the role of hyperlipi-demiardquo Journal of Lipid Research vol 46 no 10 pp 2037ndash20512005

[7] S Omoigui ldquoCholesterol synthesis is the trigger and isoprenoiddependent interleukin-6 mediated inflammation is the com-mon causative factor and therapeutic target for atheroscleroticvascular disease and age-related disorders including osteoporo-sis and type 2 diabetesrdquo Medical Hypotheses vol 65 no 3 pp559ndash569 2005

[8] K J Williams and I Tabas ldquoAtherosclerosis and inflammationrdquoScience vol 297 no 5581 pp 521ndash522 2002

[9] D Steinberg ldquoAn interpretive history of the cholesterol contro-versy Part V The discovery of the statins and the end of thecontroversyrdquo Journal of Lipid Research vol 47 no 7 pp 1339ndash1351 2006

[10] R B Singh S A Mengi Y-J Xu A S Arneja and N SDhalla ldquoPathogenesis of atherosclerosis a multifactorial pro-cessrdquo Experimental and Clinical Cardiology vol 7 no 1 pp 40ndash53 2002

[11] R Ross ldquoMechanisms of atherosclerosismdasha reviewrdquo Advancesin Nephrology from the Necker Hospital vol 19 pp 79ndash86 1990

[12] D B Cines E S Pollak C A Buck et al ldquoEndothelial cells inphysiology and in the pathophysiology of vascular disordersrdquoBlood vol 91 no 10 pp 3527ndash3561 1998

[13] P Rajendran T Rengarajan J Thangavel et al ldquoThe vascularendothelium and human diseasesrdquo International Journal ofBiological Sciences vol 9 no 10 pp 1057ndash1069 2013

[14] L Badimon J Martinez-Gonzalez V Llorente-Cortes CRodriguez and T Padro ldquoCell biology and lipoproteins inatherosclerosisrdquo Current Molecular Medicine vol 6 no 5 pp439ndash456 2006

[15] K J Williams and I Tabas ldquoThe response-to-retention hypoth-esis of early atherogenesisrdquo Arteriosclerosis Thrombosis andVascular Biology vol 15 no 5 pp 551ndash562 1995

[16] I Peluso G Morabito L Urban F Ioannone and M SerafinildquoOxidative stress in atherosclerosis development the centralrole of LDL and oxidative burstrdquo Endocrine Metabolic andImmuneDisorders Drug Targets vol 12 no 4 pp 351ndash360 2012

[17] J Steinberger S R Daniels R H Eckel et al ldquoProgress andchallenges in metabolic syndrome in children and adolescentsa scientific statement from the American Heart AssociationAtherosclerosis Hypertension and Obesity in the Young Com-mittee of the Council on Cardiovascular Disease in the YoungCouncil on Cardiovascular Nursing and Council on NutritionPhysical Activity and Metabolismrdquo Circulation vol 119 no 4pp 628ndash647 2009

[18] L Badimon G Vilahur and T Padro ldquoLipoproteins plateletsand atherothrombosisrdquoRevista Espanola de Cardiologia vol 62no 10 pp 1161ndash1178 2009

[19] K Ley Y I Miller and C C Hedrick ldquoMonocyte and macro-phage dynamics during atherogenesisrdquo Arteriosclerosis Throm-bosis and Vascular Biology vol 31 no 7 pp 1506ndash1516 2011

[20] P Libby ldquoInflammation in atherosclerosisrdquo ArteriosclerosisThrombosis and Vascular Biology vol 32 no 9 pp 2045ndash20512012

[21] D Gomez and G K Owens ldquoSmooth muscle cell phenotypicswitching in atherosclerosisrdquo Cardiovascular Research vol 95no 2 pp 156ndash164 2012

[22] P Lacolley V Regnault ANicoletti Z Li and J-BMichel ldquoThevascular smoothmuscle cell in arterial pathology a cell that cantake on multiple rolesrdquo Cardiovascular Research vol 95 no 2pp 194ndash204 2012

[23] A C Doran N Meller and C A McNamara ldquoRole ofsmooth muscle cells in the initiation and early progressionof atherosclerosisrdquo Arteriosclerosis Thrombosis and VascularBiology vol 28 no 5 pp 812ndash819 2008

[24] M Braun P Pietsch K Schror G Baumann and S B FelixldquoCellular adhesion molecules on vascular smooth muscle cellsrdquoCardiovascular Research vol 41 no 2 pp 395ndash401 1999

[25] S Ma D Yang D Li B Tang and Y Yang ldquoOleic acid inducessmooth muscle foam cell formation and enhances atheroscle-rotic lesion development via CD36rdquo Lipids in Health andDisease vol 10 article 53 2011

[26] N Platt R Haworth L Darley and S Gordon ldquoThemany rolesof the class A macrophage scavenger receptorrdquo InternationalReview of Cytology vol 212 pp 1ndash40 2002

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 13: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 13

[27] R E Clempus and K K Griendling ldquoReactive oxygen speciessignaling in vascular smooth muscle cellsrdquo CardiovascularResearch vol 71 no 2 pp 216ndash225 2006

[28] L Hegyi J N Skepper N R Cary andM J Mitchinson ldquoFoamcell apoptosis and the development of the lipid core of humanatherosclerosisrdquo The Journal of Pathology vol 180 no 4 pp423ndash429 1996

[29] B L Gerber ldquoIn vivo evaluation of atherosclerotic plaqueinflammation and of anti-inflammatory effects of statins by 18F-fluorodeoxyglucose positron emission tomographyrdquo Journal ofthe American College of Cardiology vol 62 no 10 pp 918ndash9202013

[30] E Thorp and I Tabas ldquoMechanisms and consequences ofefferocytosis in advanced atherosclerosisrdquo Journal of LeukocyteBiology vol 86 no 5 pp 1089ndash1095 2009

[31] R R S Packard and P Libby ldquoInflammation in atherosclerosisfrom vascular biology to biomarker discovery and risk predic-tionrdquo Clinical Chemistry vol 54 no 1 pp 24ndash38 2008

[32] F Grover-Paez and A B Zavalza-Gomez ldquoEndothelial dys-function and cardiovascular risk factorsrdquoDiabetes Research andClinical Practice vol 84 no 1 pp 1ndash10 2009

[33] R Natarajan and Q Cai ldquoMonocyte retention in the pathologyof atherosclerosisrdquo Future Cardiology vol 1 no 3 pp 331ndash3402005

[34] H Kanda S Tateya Y Tamori et al ldquoMCP-1 contributes tomacrophage infiltration into adipose tissue insulin resistanceand hepatic steatosis in obesityrdquoThe Journal of Clinical Investi-gation vol 116 no 6 pp 1494ndash1505 2006

[35] C Zhang ldquoThe role of inflammatory cytokines in endothelialdysfunctionrdquo Basic Research in Cardiology vol 103 no 5 pp398ndash406 2008

[36] EGalkina andK Ley ldquoImmune and inflammatorymechanismsof atherosclerosisrdquo Annual Review of Immunology vol 27 pp165ndash197 2009

[37] P Libby ldquoInflammation in atherosclerosisrdquoNature vol 420 no6917 pp 868ndash874 2002

[38] P Libby ldquoMolecular and cellular mechanisms of the thromboticcomplications of atherosclerosisrdquoThe Journal of Lipid Researchvol 50 pp S352ndashS357 2009

[39] C Tian R Zhang X Ye et al ldquoResveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae viaVEGFKDRpathwayrdquoGenes andNutrition vol 8 no 2 pp 231ndash239 2013

[40] D H Choi Y J Lee H C Oh et al ldquoImproved endothelialdysfunction by Cynanchum wilfordii in Apolipoprotein Eminusminusmice fed a high fatcholesterol dietrdquo Journal of Medicinal Foodvol 15 no 2 pp 169ndash179 2012

[41] Y-L Xing Z Zhou Z-Y Zhong et al ldquoProtocatechuicaldehyde inhibits lipopolysaccharide-induced human umbilicalvein endothelial cell apoptosis via regulation of caspase-3rdquoPhytotherapy Research vol 26 no 9 pp 1334ndash1341 2012

[42] K-P Ang H-K Tan M Selvaraja et al ldquoCryptotanshinoneattenuates in vitro oxLDL-induced pre-lesional atheroscleroticeventsrdquo Planta Medica vol 77 no 16 pp 1782ndash1787 2011

[43] Y J Lee M K Moon S M Hwang et al ldquoAnti-inflammatoryeffect of buddleja officinalis on vascular inflammation in humanumbilical vein endothelial cellsrdquo The American Journal ofChinese Medicine vol 38 no 3 pp 585ndash598 2010

[44] MAAltugTuncer B Yaymaci L Sati et al ldquoInfluence ofTribu-lus terrestris extract on lipid profile and endothelial structurein developing atherosclerotic lesions in the aorta of rabbits on

a high-cholesterol dietrdquo Acta Histochemica vol 111 no 6 pp488ndash500 2009

[45] J-B Wan S M-Y Lee J-D Wang et al ldquoPanax notoginsengreduces atherosclerotic lesions in ApoE-deficient mice andinhibits TNF-120572-induced endothelial adhesionmolecule expres-sion and monocyte adhesionrdquo Journal of Agricultural and FoodChemistry vol 57 no 15 pp 6692ndash6697 2009

[46] Y-H Chen S-J Lin Y-L Chen P-L Liu and J-W ChenldquoAnti-inflammatory effects of different drugsagents withantioxidant property on endothelial expression of adhesionmoleculesrdquoCardiovascular andHematological DisordersmdashDrugTargets vol 6 no 4 pp 279ndash304 2006

[47] J-W Chen Y-H Chen F-Y Lin Y-L Chen and S-J LinldquoGinkgo biloba extract inhibits tumor necrosis factor-120572-inducedreactive oxygen species generation transcription factor activa-tion and cell adhesion molecule expression in human aorticendothelial cellsrdquo Arteriosclerosis Thrombosis and VascularBiology vol 23 no 9 pp 1559ndash1566 2003

[48] K Steinkamp-Fenske L Bollinger N Voller et al ldquoUrsolicacid from the Chinese herb Danshen (Salvia miltiorrhizaL) upregulates eNOS and downregulates Nox4 expression inhuman endothelial cellsrdquo Atherosclerosis vol 195 no 1 ppe104ndashe111 2007

[49] D-I Sun I T Nizamutdinova Y M Kim et al ldquoBisacuroneinhibits adhesion of inflammatory monocytes or cancer cells toendothelial cells through down-regulation of VCAM-1 expres-sionrdquo International Immunopharmacology vol 8 no 9 pp1272ndash1281 2008

[50] S-C Chen Y-L Chang D L Wang and J-J Cheng ldquoHerbalremedy magnolol suppresses IL-6-induced STAT3 activationand gene expression in endothelial cellsrdquo British Journal ofPharmacology vol 148 no 2 pp 226ndash232 2006

[51] Y-H Chen S-J Lin J-W Chen H-H Ku and Y-L ChenldquoMagnolol attenuates VCAM-1 expression in vitro in TNF-120572-treated human aortic endothelial cells and in vivo in the aortaof cholesterol-fed rabbitsrdquo British Journal of Pharmacology vol135 no 1 pp 37ndash47 2002

[52] M Ding G-R Zhao Y-J Yuan and Z-X Guo ldquoAqueousextract of Salvia miltiorrhoza regulates adhesion moleculeexpression of tumor necrosis factor 120572-induced endothelialcells by blocking activation of nuclear factor 120581Brdquo Journal ofCardiovascular Pharmacology vol 45 no 6 pp 516ndash524 2005

[53] Y-H Chen S-J Lin H-H Ku et al ldquoSalvianolic acid Battenuates VCAM-1 and ICAM-1 expression in TNF-120572-treatedhuman aortic endothelial cellsrdquo Journal of Cellular Biochemistryvol 82 no 3 pp 512ndash521 2001

[54] Y Zhang Y Si S Yao et al ldquoCelastrus orbiculatus thunbdecreases athero-susceptibility in lipoproteins and the aorta ofGuinea pigs fed high fat dietrdquo Lipids vol 48 no 6 pp 619ndash6312013

[55] Y Bao L Wang Y Xu et al ldquoSalvianolic acid B inhibitsmacrophage uptake of modified low density lipoprotein(mLDL) in a scavenger receptor CD36-dependent mannerrdquoAtherosclerosis vol 223 no 1 pp 152ndash159 2012

[56] D H Choi Y J Lee J S Kim D G Kang and H S LeeldquoCynanchum wilfordii ameliorates hypertension and endothe-lial dysfunction in rats fed with high fatcholesterol dietsrdquoImmunopharmacology and Immunotoxicology vol 34 no 1 pp4ndash11 2012

[57] S Subramaniam R Subramaniam S Rajapandian S Uthrap-athi V R Gnanamanickam and G P Dubey ldquoAnti-atherogenicactivity of ethanolic fraction of terminalia arjuna bark on

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 14: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

14 Evidence-Based Complementary and Alternative Medicine

hypercholesterolemic rabbitsrdquo Evidence-Based Complementaryand Alternative Medicine vol 2011 Article ID 487916 8 pages2011

[58] N J Dinani S Asgary H Madani G H Naderi and PMahzoni ldquoHypocholesterolemic and antiatherosclerotic effectof Artemisia aucheri in hypercholesterolemic rabbitsrdquo PakistanJournal of Pharmaceutical Sciences vol 23 no 3 pp 321ndash3252010

[59] H-X Ni N-J Yu and X-H Yang ldquoThe study of ginsenosideon PPAR120574 expression of mononuclear macrophage in type 2diabetesrdquo Molecular Biology Reports vol 37 no 6 pp 2975ndash2979 2010

[60] S Amrani H Harnafi N E H Bouanani et al ldquoHypolipi-daemic activity of aqueous Ocimum basilicum extract in acutehyperlipidaemia induced by triton WR-1339 in rats and itsantioxidant propertyrdquo Phytotherapy Research vol 20 no 12 pp1040ndash1045 2006

[61] S H Nile and S W Park ldquoHPTLC analysis antioxidantanti-inflammatory and antiproliferative activities of Arisaematortuosum tuber extractrdquo Pharmaceutical Biology vol 52 no 2pp 221ndash227 2014

[62] S Pandeti R Sonkar A Shukla G Bhatia and N TadigoppulaldquoSynthesis of new andrographolide derivatives and evaluationof their antidyslipidemic LDL-oxidation and antioxidant activ-ityrdquo European Journal of Medicinal Chemistry vol 69 pp 439ndash448 2013

[63] J-K Li R Ge L Tang and Q-S Li ldquoProtective effectsof farrerol against hydrogen-peroxide-induced apoptosis inhuman endothelium-derived EAhy926 cellsrdquoCanadian Journalof Physiology and Pharmacology vol 91 no 9 pp 733ndash740 2013

[64] L-Q Jia G-L Yang L Ren et al ldquoTanshinone IIA reducesapoptosis induced by hydrogen peroxide in the humanendothelium-derived EAhy926 cellsrdquo Journal of Ethnopharma-cology vol 143 no 1 pp 100ndash108 2012

[65] S Xu Z Liu Y Huang et al ldquoTanshinone II-A inhibitsoxidized LDL-induced LOX-1 expression in macrophages byreducing intracellular superoxide radical generation andNF-120581Bactivationrdquo Translational Research vol 160 no 2 pp 114ndash1242012

[66] S Gao Z Liu H Li P J Little P Liu and S Xu ldquoCardiovascularactions and therapeutic potential of tanshinone IIArdquoAtheroscle-rosis vol 220 no 1 pp 3ndash10 2012

[67] Y-I Li G Elmer and R C LeBoeuf ldquoTanshinone IIA reducesmacrophage death induced by hydrogen peroxide by upregulat-ing glutathione peroxidaserdquo Life Sciences vol 83 no 15-16 pp557ndash562 2008

[68] Y-C Hung P-WWang and T-L Pan ldquoFunctional proteomicsreveal the effect of Salvia miltiorrhiza aqueous extract againstvascular atherosclerotic lesionsrdquo Biochimica et Biophysica ActaProteins and Proteomics vol 1804 no 6 pp 1310ndash1321 2010

[69] N P Visavadiya B Soni N Dalwadi and D MadamwarldquoChlorophytum borivilianum as potential terminator of freeradicals in various in vitro oxidation systemsrdquo Drug andChemical Toxicology vol 33 no 2 pp 173ndash182 2010

[70] T-L Yang F-Y Lin Y-H Chen et al ldquoSalvianolic acidB inhibits low-density lipoprotein oxidation and neointimalhyperplasia in endothelium-denuded hypercholesterolaemicrabbitsrdquo Journal of the Science of Food and Agriculture vol 91no 1 pp 134ndash141 2011

[71] Y-L Chen C-S Hu F-Y Lin et al ldquoSalvianolic acid B attenu-ates cyclooxygenase-2 expression in vitro in LPS-treated human

aortic smooth muscle cells and in vivo in the apolipoprotein-E-deficient mouse aortardquo Journal of Cellular Biochemistry vol 98no 3 pp 618ndash631 2006

[72] S J Lin I T Lee Y H Chen et al ldquoSalvianolic acid B attenuatesMMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aorticsmooth muscle cellsrdquo Journal of Cellular Biochemistry vol 100no 2 pp 372ndash384 2007

[73] Y-JWu C-Y Hong S-J Lin PWu andM-S Shiao ldquoIncreaseof vitamin e content in LDL and reduction of atherosclerosisin cholesterol-fed rabbits by a water-soluble antioxidant-richfraction of SalviamiltiorrhizardquoArteriosclerosisThrombosis andVascular Biology vol 18 no 3 pp 481ndash486 1998

[74] H-J Park ldquoChemistry and pharmacological action of caf-feoylquinic acid derivatives and pharmaceutical utilizationof chwinamul (Korean Mountainous Vegetable)rdquo Archives ofPharmacal Research vol 33 no 11 pp 1703ndash1720 2010

[75] H Ma X He Y Yang M Li D Hao and Z Jia ldquoThegenus Epimedium an ethnopharmacological and phytochem-ical reviewrdquo Journal of Ethnopharmacology vol 134 no 3 pp519ndash541 2011

[76] O Potterat ldquoGoji (Lycium barbarum and L chinense) phy-tochemistry pharmacology and safety in the perspective oftraditional uses and recent popularityrdquo Planta Medica vol 76no 1 pp 7ndash19 2010

[77] M Broncel ldquoAntiatherosclerotic properties of flavones from theroots of Scutellaria baicalensis Georgirdquo Wiadomosci Lekarskievol 60 no 5-6 pp 294ndash297 2007

[78] M Zhou H Xu L Pan J Wen Y Guo and K ChenldquoEmodin promotes atherosclerotic plaque stability in fat-fedapolipoprotein E-deficient micerdquo Tohoku Journal of Experimen-tal Medicine vol 215 no 1 pp 61ndash69 2008

[79] W Duan Y Yu and L Zhang ldquoAntiatherogenic effects ofPhyllanthus Emblica associated with corilagin and its analoguerdquoYakugaku Zasshi vol 125 no 7 pp 587ndash591 2005

[80] M-J Wu C-L Huang T-W Lian M-C Kou and L WangldquoAntioxidant activity of Glossogyne tenuifoliardquo Journal of Agri-cultural and FoodChemistry vol 53 no 16 pp 6305ndash6312 2005

[81] I T Nizamutdinova H M Oh Y N Min et al ldquoPaeonol sup-presses intercellular adhesion molecule-1 expression in tumornecrosis factor-120572-stimulated human umbilical vein endothelialcells by blocking p38 ERK and nuclear factor-120581B signalingpathwaysrdquo International Immunopharmacology vol 7 no 3 pp343ndash350 2007

[82] A Gugliucci and T Menini ldquoThree different pathways forhuman LDL oxidation are inhibited in vitro by water extractsof the medicinal herbAchyrocline satureoidesrdquo Life Sciences vol71 no 6 pp 693ndash705 2002

[83] T H Park D H Kim C H Kim et al ldquoPeroxynitritescavengingmode of alaternin isolated fromCassia torardquo Journalof Pharmacy and Pharmacology vol 56 no 10 pp 1315ndash13212004

[84] K Chan S H Chui D Y LWongW Y Ha C L Chan and RN S Wong ldquoProtective effects of Danshensu from the aqueousextract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunctionrdquo Life Sciences vol 75 no 26pp 3157ndash3171 2004

[85] L Li L-P Jiao and B H Lau ldquoProtective effect of gypenosidesagainst oxidative stress in phagocytes vascular endothelial cellsand liver microsomesrdquoCancer Biotherapy vol 8 no 3 pp 263ndash272 1993

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 15: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Evidence-Based Complementary and Alternative Medicine 15

[86] H-C Huang H-R Wang and L-M Hsieh ldquoAntiproliferativeeffect of baicalein a flavonoid from a Chinese herb on vascularsmooth muscle cellrdquo European Journal of Pharmacology vol251 no 1 pp 91ndash93 1994

[87] Y-L Chen H-C Huang Y-I Weng Y-J Yu and Y-TLee ldquoMorphological evidence for the antiatherogenic effect ofscoparone in hyperlipidaemic diabetic rabbitsrdquo CardiovascularResearch vol 28 no 11 pp 1679ndash1685 1994

[88] P Chan and B Tomlinson ldquoAntioxidant effects of Chinesetraditional medicine focus on trilinolein isolated from theChinese herb sanchi (Panax pseudoginseng)rdquo The Journal ofClinical Pharmacology vol 40 no 5 pp 457ndash461 2000

[89] L Gu W Bai S Li et al ldquoCelastrol prevents atherosclerosis viainhibiting LOX-1 and oxidative stressrdquo PLoS ONE vol 8 no 6Article ID e65477 2013

[90] M F Andreasen A-K Landbo L P Christensen A Hansenand A S Meyer ldquoAntioxidant effects of phenolic rye (Secalecereale L) extracts monomeric hydroxycinnamates and ferulicacid dehydrodimers on human low-density lipoproteinsrdquo Jour-nal of Agricultural and Food Chemistry vol 49 no 8 pp 4090ndash4096 2001

[91] S H Park H J Koo Y Y Sung and H K Kim ldquoThe protectiveeffect of Prunella vulgaris ethanol extract against vascularinflammation in TNF-120572-stimulated human aortic smoothmus-cle cellsrdquo BMB Reports vol 46 no 7 pp 352ndash357 2013

[92] F Wang Q Gao S Guo et al ldquoThe sonodynamic effectof curcumin on THP-1 cell-derived macrophagesrdquo BioMedResearch International vol 2013 Article ID 737264 9 pages2013

[93] C Y Moon C R Ku Y H Cho and E J Lee ldquoProtocate-chuic aldehyde inhibits migration and proliferation of vascularsmoothmuscle cells and intravascular thrombosisrdquoBiochemicaland Biophysical Research Communications vol 423 no 1 pp116ndash121 2012

[94] S-J Lee S-S Park W-J Kim and S-K Moon ldquoGleditsiasinensis thorn extract inhibits proliferation and TNF-120572-inducedMMP-9 expression in vascular smooth muscle cellsrdquo TheAmerican Journal of Chinese Medicine vol 40 no 2 pp 373ndash386 2012

[95] T-J Kim J-H Lee J-J Lee et al ldquoCorynoxeine isolatedfrom the hook of Uncaria rhynchophylla inhibits rat aorticvascular smooth muscle cell proliferation through the blockingof extracellular signal regulated kinase 12 phosphorylationrdquoBiological and Pharmaceutical Bulletin vol 31 no 11 pp 2073ndash2078 2008

[96] K-W Liang C-T Ting S-C Yin et al ldquoBerberine suppressesMEKERK-dependent Egr-1 signaling pathway and inhibitsvascular smooth muscle cell regrowth after in vitro mechanicalinjuryrdquo Biochemical Pharmacology vol 71 no 6 pp 806ndash8172006

[97] H H Ho L S Hsu K C Chan H M Chen C H Wuand C J Wang ldquoExtract from the leaf of nucifera reducedthe development of atherosclerosis via inhibition of vascularsmooth muscle cell proliferation and migrationrdquo Food andChemical Toxicology vol 48 no 1 pp 159ndash168 2010

[98] C-C Chen J-D Hsu S-F Wang et al ldquoHibiscus sabdar-iffa extract inhibits the development of atherosclerosis incholesterol-fed rabbitsrdquo Journal of Agricultural and Food Chem-istry vol 51 no 18 pp 5472ndash5477 2003

[99] Z Yuan Y Liao G Tian et al ldquoPanax notoginseng saponinsinhibit Zymosan A induced atherosclerosis by suppressing

integrin expression FAK activation and NF-120581B translocationrdquoJournal of Ethnopharmacology vol 138 no 1 pp 150ndash155 2011

[100] Y-F Wang X-F Yang B Cheng et al ldquoProtective effect ofastragalus polysaccharides on ATP binding cassette transporterA1 in THP-1 derived foam cells exposed to tumor necrosisfactor-alphardquo Phytotherapy Research vol 24 no 3 pp 393ndash3982010

[101] M Napagoda J Gerstmeier S Wesely et al ldquoInhibitionof 5-lipoxygenase as anti-inflammatory mode of action ofPlectranthus zeylanicus Benth and chemical characterizationof ingredients by a mass spectrometric approachrdquo Journal ofEthnopharmacology vol 151 no 2 pp 800ndash809 2014

[102] W Yao W Fan C Huang H Zhong X Chen and WZhang ldquoProteomic analysis for anti-atherosclerotic effect oftetrahydroxystilbene glucoside in ratsrdquo Biomedicine amp Pharma-cotherapy vol 67 no 2 pp 140ndash145 2013

[103] S C Chen Y L Lin B Huang D L Wang and J J ChengldquoSalvianolic acid B suppresses IFN-120574-induced JAKSTAT1 acti-vation in endothelial cellsrdquoThrombosis Research vol 128 no 6pp 560ndash564 2011

[104] K D Tsai S M Yang J C Lee et al ldquoPanax notoginsengattenuates bleomycin-induced pulmonary fibrosis in micerdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 404761 7 pages 2011

[105] A Sun H Liu S Wang et al ldquoSalvianolic acid B suppressesmaturation of human monocyte-derived dendritic cells byactivating PPAR120574rdquo British Journal of Pharmacology vol 164 no8 pp 2042ndash2053 2011

[106] Z Zhou Y Liu A-DMiao and S-QWang ldquoSalvianolic acid Battenuates plasminogen activator inhibitor type 1 production inTNF-120572 treated human umbilical vein endothelial cellsrdquo Journalof Cellular Biochemistry vol 96 no 1 pp 109ndash116 2005

[107] Y Wang Z Huang L Wang et al ldquoThe anti-malarialartemisinin inhibits pro-inflammatory cytokines via the NF-120581B canonical signaling pathway in PMA-induced THP-1mono-cytesrdquo International Journal of Molecular Medicine vol 27 no2 pp 233ndash241 2011

[108] Y-N Liu S-L Pan C-H Liao et al ldquoEvodiamine represseshypoxia-induced inflammatory proteins expression andhypoxia-inducible factor 1120572 accumulation in RAW2647rdquoShock vol 32 no 3 pp 263ndash269 2009

[109] C-F Chen and C-H Cheng ldquoRegulation of cellular meta-bolism and cytokines by the medicinal herb feverfew inthe human monocytic THP-1 cellsrdquo Evidence-Based Comple-mentary and Alternative Medicine vol 6 no 1 pp 91ndash98 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom

Page 16: Review Article Chinese Herbal Compounds for the Prevention and …downloads.hindawi.com/journals/ecam/2015/752610.pdf · 2019-07-31 · Review Article Chinese Herbal Compounds for

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

MEDIATORSINFLAMMATION

of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Behavioural Neurology

EndocrinologyInternational Journal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Disease Markers

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

BioMed Research International

OncologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Oxidative Medicine and Cellular Longevity

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Computational and Mathematical Methods in Medicine

OphthalmologyJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Diabetes ResearchJournal of

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Research and TreatmentAIDS

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Gastroenterology Research and Practice

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom