EditorialTherapeutic Potential of Natural Antioxidants

Kota V. Ramana ,1 Aramati B. M. Reddy,2N. V. Ravi KumarMajeti,3 and Sharad S. Singhal4

1Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA2Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, TS 500046, India3Department of Pharmaceutical Sciences, Irma Lerma Rangel College of Pharmacy, Texas A&M University, College Station,TX 77843, USA4Department of Medical Oncology, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USA

Correspondence should be addressed to Kota V. Ramana; kvramana@utmb.edu

Received 30 May 2018; Accepted 30 May 2018; Published 15 August 2018

Copyright © 2018 Kota V. Ramana et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Natural antioxidants are the plants- and other livingorganism-derived compounds with a strong potential toinhibit oxidative stress by controlling the formation of freeradicals, scavenging the free radicals, interrupting the freeradical-mediated chain reactions, and preventing the lipidperoxidation process. Thus, natural antioxidants have poten-tial to balance the irregulated oxidative stress and to restorethe cellular homeostasis. Therefore, natural antioxidantscan decrease the deleterious effects of various oxidativestress-induced pathological conditions. The practice of usingcrude natural plant products to treat multiple diseases isancestrally going on for thousands of years without or withthe knowledge of their active antioxidant molecules wellbefore the development of modern medicine with syntheticdrugs and antioxidants. Indeed, after careful preclinical andclinical studies, most of the plant products have now beenshown to act as potential therapeutic agents in preventingvarious human pathologies such as diabetes, aging, neurolog-ical, cardiovascular, and cancer. Furthermore, increase in thetechnical advancements made possible to identify vital activeingredients from the natural sources and develop them aspotential therapeutic agents. Nowadays, an increase in theawareness of a healthy lifestyle has resulted in everydayconsumption of nutritionally rich antioxidant organic natu-ral food products over synthetic and processed foods whichcould restore our body’s ability to fight against various kindsof stresses, infections, and related pathologies. Therefore,identification and development of novel antioxidants from

nature could be beneficial in limiting the deleterious effectsof oxidative stress in different pathological conditions.With this goal, we brought this special issue that reportsthe past and current research focused on identifying aswell as understanding the mechanistic role of various anti-oxidants from the natural sources with a potential forfuture therapeutic development.

This special issue on “Therapeutic Potential of NaturalAntioxidants” compiles 27 exceptional scientific manuscriptsincluding eighteen research articles and nine review articles,which provide comprehensive evidence demonstrating thetherapeutic significance of natural antioxidants in variouspathological conditions.

The nine review articles of this issue describe thetherapeutic potential of various natural antioxidants, possiblemechanisms of action, and role in controlling oxidativestress-induced inflammatory signaling and pathologies. Thereview article by J. Kocot et al. nicely described the role ofnatural honey bees products specifically propolis, bee pollen,and royal jelly in counteracting the oxidative stress in varioushuman diseases and mechanism of action. Further, in thisexcellent review article, authors have highlighted the influ-ence of bee species, geographical location, and extractionmethods on the composition of the bee product as well astheir effectiveness as therapeutic agents. Similarly, S. Ahmedet al. in-depth discussed molecular mechanisms throughwhich honey exhibits several medicinal and health benefits.Specifically, they discussed various cell signaling pathways

HindawiOxidative Medicine and Cellular LongevityVolume 2018, Article ID 9471051, 3 pageshttps://doi.org/10.1155/2018/9471051

that lead to apoptosis, proliferation, and regulation ofinflammatory response. Another interesting review articleby A. Baptista et al. has addressed antimicrobial and antiox-idant properties of cashew (Anacardium occidentale), cajui(Anacardium microcarpum), and pequi (Caryocar brasi-liense). This review described the analysis of data from adatabase of published studies on these compounds. Theirreport suggests that most of the studied species have shownsignificant antioxidant and antimicrobial properties.

The review article by M.Wojcik et al. described how anti-oxidative and anti-inflammatory properties of ancestrallywell-known plant product curcumin beneficial for treatingdiabetes and cancer. In this article, authors have done an out-standing job in describing the current research on molecularsignaling pathways through which curcumin exerted its anti-cancer and antidiabetic activities and discussed the necessityof its further therapeutic development.

Polyphenols naturally found in the fruits and vegetableshave been shown to exhibit pleiotropic health benefits inpreventing various human diseases such as diabetes, cancer,asthma, and cardiovascular. An excellent review article byS. Li et al. discussed how various polyphenols isolated frommultiple natural sources help in the prevention of liverdiseases. Further, they discussed the possible mechanismsof actions through which these natural polyphenols decreaseliver diseases in vitro and in vivo animal models and clinicalstudies. Similarly, plant flavonoids with their potential anti-oxidative and anti-inflammatory actions prevent a numberof diseases including diabetes, cancer, and cardiovascular.Recent investigations also suggest their beneficial role indepressive disorders. L. Hritcu et al. nicely reviewed variousantidepressant flavonoids and their antioxidant potential.They further discussed the mechanism of action of flavo-noids and how they combat the oxidative stress-induceddepressive diseases. Ginseng is a natural plant product widelyused in Asian countries for its anticancer and immunomod-ulatory activities. Q. Zheng et al. have discussed the role ofginsenoside Rb1, a major pharmacological extract fromginseng, in myocardial infarction. The review based on ameta-analysis of published information from scientific data-bases indicate that ginsenoside Rb1 possess cardioprotectiveactions in acute myocardial infarction largely due to its anti-oxidative, anti-inflammatory, and antiapoptotic propertiesand suggest that it could be an ideal candidate for furtherdevelopment for use in cardiovascular complications. In thesame contest of cardiovascular complications, J. Tian et al.have discussed the role of various herbal medicines in dia-betic cardiomyopathy. Specifically, they discussed the roleand mechanism of actions of various natural flavonoids andothers such as triptolide, curcumin, Ginkgo biloba extract,resveratrol, astragalus polysaccharides, Salvia miltiorrhiza,and ginseng. A final review article by X. Su et al. hasdescribed anticancer activities of sulforaphane, a naturalantioxidant derived from cruciferous vegetables. Specifically,they discussed the role of sulforaphane in Nrf2 activation andits mediated antioxidative pathways. They have alsodescribed how this natural antioxidant reverses epigeneticalterations in cancers by targeting DNA methyltransferases,histone diacetyltransferases, and noncoding RNAs.

The research article by X. Liu et al. investigates theeffect of isoliquiritigenin, a natural flavonoid compoundderived from the herb licorice root, in the prevention ofmild and acute pancreatitis in mouse models. Specifically,in caerulein-induced mild pancreatitis and L-arginine-induced acute pancreatitis mouse models, treatment of isoli-quiritigenin shows significant beneficial effects. This studysuggests that by inhibiting the oxidative stress and modulat-ing the Nrf2/HO-1 pathways, isoliquiritigenin could preventacute pancreatitis. Article by J. Benites et al. has reportedanti-Helicobacter pylori activities of a series of 2- and 3-phenylaminojuglone-based substances prepared fromjuglone (extract of the husk of walnut fruit). They identifieda most active compound 2-((3,4,5-trimethoxyphenyl)a-mino)-5-hydroxynaphthalene-1,4-dione 7 has potential anti-bacterial activity at low concentration. In another study byS.-H. Cha et al. reports protective effects of diphlorethohy-droxycarmalol (DPHC), a polyphenol isolated from edibleseaweed (Ishige okamurae) on methylglyoxal-induced oxi-dative stress in human embryonic kidney cells. They havealso shown that DPHC increases the activation of Nrf2transcription factor and expression of antioxidativeenzymes. Further, DPHC also decreases the formation ofadvanced glycation end products and increases glyoxalase-1. These results suggest that DPHC could be developedfurther as potential therapeutic agent for the prevention ofdiabetic nephropathy.

A research report by I. Castellano et al. has demonstratedhow anti-inflammatory activities of ovothiol A, a naturalantioxidant isolated from sea urchin eggs, preventshyperglycemia-induced endothelial dysfunction. They haveshown that ovothiol A prevents TNF-alpha-induced mono-cyte adhesion to the human umbilical vascular endothelialcell (HUVEC), reactive oxygen, and nitrogen species andincreases NO bioavailability. These results suggest a potentialtherapeutic use of this compound for the prevention of car-diovascular complications associated with the endothelialdysfunction. In the same lines, H. Sonowal et al. also reportedhow anti-inflammatory actions of Vialinin A, a p-terphenylcompound derived from Chinese edible mushroom T.terrestris and T. vialis, prevents endothelial dysfunctionand neovascularization in vitro and in vivomodels. Explicitly,they have shown that Vialinin A prevents VEGF-inducedoxidative stress signals that activate NF-κB mediated inflam-matory response in HUVECs. They have also demonstratedthat in a mouse model of Matrigel plug assay, Vialinin Aprevents the formation of new blood vessels. These studiessuggest that Vialinin A exhibits potent antioxidative andantiangiogenic properties.

Studies by A. Micali et al. demonstrated the protectiveeffects of flavocoxid, a natural antioxidative flavonoid, oncadmium-induced renal toxicity. Specifically, they haveshown that flavocoxid prevents cadmium-induced ureanitrogen and creatinine, iNOS, MMP-9, and pERK 1/2expression. They have also demonstrated that this flavonoidpreserved the glomerular and tubular structural and ultra-structural changes in cadmium-induced renal tissues in mice.These studies indicate protective effects of flavocoxid oncadmium-induced organ toxicities. The research article by

2 Oxidative Medicine and Cellular Longevity

Y. Xiang et al. investigates how quassinoid brusatol, isolatedfrom the Brucea javanica plant, increases the chemothera-peutic efficacy of gemcitabine in pancreatic cancer. Brusatolprevents the growth of pancreatic cancer cells in culture aswell as in nude mice xenograft models. Precisely, they haveshown that brusatol inhibits Nrf2-mediated antioxidativepathways and increases reactive oxygen species (ROS). Theresults provide some evidence that brusatol could be usedas an adjuvant therapy along with gemcitabine in preventingpancreatic cancer. Similarly, another study by L. Cheng et al.demonstrates that resveratrol increases the chemotherapeu-tic efficacy of gemcitabine in pancreatic cancer cells. Thisstudy indicates that resveratrol inhibits the expression ofNAF-1 and increases ROS and Nrf2 signaling.

The article by H. Wu et al. determined the effect ofresveratrol in promoting angiogenesis of endothelial pro-genitor cells (EPCs). They have shown that antioxidantactions of resveratrol suppressed the syndecan 4 sheddingand increased tube formation of late EPCs via syndecan4/Akt/eNOS pathway. M. Lee et al. reported the anti-inflammatory effects of black ginger (Kaempferia parvi-flora) on solar UV light irradiation-induced damage onmouse skin tissue. They have shown that this plant extractprevents UV-induced oxidative stress, expression of COX-2and activation of MAPK signaling. This studies also foundgallic acid, apigenin, and tangeretin as the major polyphenolsin the extract. Another research study by R. Liu et al. demon-strated antioral cancer efficacy of melatonin. They haveshown that melatonin inhibits the proliferation and apopto-tic resistance of the oral cancer cells by regulating the ROS/Akt/cyclin D1/PCNA/Bcl-2/Bax signals. Another researcharticle by D. Zhang et al. demonstrated a potent antioxidantactivity of echinacoside, a phenylethanoid glycoside isolatedfrom Herba Cistanches. In this study, BALB/c mice andHaCaT cells were pretreated with echinacoside followed byUVB exposure. They found that echinacoside prevents theskin injury, oxidative stress, DNA damage, and apoptosiscaused by UVB exposure and also normalized the proteinlevels of ATR, p53, PIAS3, hnRNP K, PARP, and XPA. Thisreport provides significance of this natural antioxidant in theprevention of UVB-induced DNA damage of the skin.

D. K. Yang and S.-J. Kim have reported protective effectsof cucurbitacin I, a triterpenoid natural antioxidant, onhydrogen peroxide-induced H9c2 cardiomyoblast cytotoxic-ity. Specifically, this study demonstrates that cucurbitacin Iprevents H2O2-induced oxidative stress, restores mitochon-drial functions, and inhibits apoptotic response in H9c2 cells.Further, it also blocked the H2O2-induced activation ofextracellular signal-regulated kinase 1/2, c-Jun N-terminalkinase, and p38 MAPK. This report provides an excellentevidence of how this natural antioxidant could exhibit a pro-tective effect on oxidant-induced cardiac injury. L. Zhanget al. in their research article examined the effects of flavo-noids extracted from Citrus aurantium in controlling theosteosarcoma progression. Results indicate that naringeninnot naringin and hesperetin inhibited the growth of MG-63cells which seems to be due to the potent antioxidant actionof naringenin as compared to others. Most importantly, asmall-scale clinical study using 95 osteosarcoma patients

treated with naringenin showed a significant decrease in theosteosarcoma volume and their reoccurrence in a two-yearfollow-up. These studies provide concluding evidence forthe therapeutic development of this natural antioxidant.

Another interesting research article by C. Guan et al.reports the immunosuppressive effect of antroquinonol, aubiquinone derivative from the mushroom Antrodia cam-phorata, on CD8+ T cell proliferation and activation resistto depigmentation induced by hydrogen peroxide. They haveantroquinonol that inhibits proliferation of CD8+ T cells bysuppressing the production of cytokines IL-2 and IFN-γand T cell activation markers CD69 and CD137 in vitro. Fur-ther, antroquinonol decreased hydrogen peroxide-inducedCD8+ T cell infiltration in mice skin inhibited the productionof IL-2 and IFN-γ and reduced the expression of CXCL10and CXCR3. Thus, this study reports a novel immunomodu-latory role of a natural antioxidant, antroquinonol. C. M. dosSantos et al. have investigated the chemical composition ofthe geopropolis of Melipona quadrifasciata anthidioides.They have shown antioxidant, antimutagenic, anti-inflam-matory, and antimicrobial activities of these compositions.In another study, V. T. Chagas et al. also characterized thechemical composition of polyphenol-rich extracts of Syzy-gium cumini leaves. Specifically, they identified antidiabeticeffects of these compounds in alloxan-induced diabetes inrats. Their results suggest that this plant extract could preventantidiabetic activities by preventing the lipoxygenase activityand stimulating pancreatic insulin-secreting beta cells.Another study by U. P. dos Santos et al. characterized thelipophilic antioxidants and fatty acids from Hancorniaspeciosa leaves. Further, they examined the antidiabeticeffects of ethanolic extract of H. speciosa extracts in diabeticWister rats. Additionally, they have also examined microbio-logical quality and safety of H. speciosa leaves as well as anti-oxidant and antimutagenic activities.

It is evident from these papers that natural antioxidantsplay a major role in stabilizing the oxidative stress deregu-lated critical cellular pathways involved in the pathophysiol-ogy of a number of pathological disorders. Most of thearticles reported a novel role of natural antioxidants in dis-ease prevention and suggested potential future therapeuticdevelopment. The current change in the healthy lifestyleadvocates search for more natural antioxidants with strongtherapeutic potential which can eventually replace with somesynthetic drugs with unwanted side effects. Thus, identifica-tion and development of natural antioxidants not only playan essential role in the prevention or therapy of human dis-eases but also interrupt any adversity that disrupts normalhuman health.

Acknowledgments

We would like to thank all the editorial staff, authors, andreviewers who took part in the success of this special issue.

Kota V. RamanaAramati B. M. Reddy

N. V. Ravi Kumar MajetiSharad S. Singhal

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