Beneficial Role of Bitter Melon Supplementation in Obesity ... · ReviewArticle Beneficial Role of...

Review ArticleBeneficial Role of Bitter Melon Supplementation in Obesity andRelated Complications in Metabolic Syndrome

Md Ashraful Alam1 Riaz Uddin2 Nusrat Subhan3 Md Mahbubur Rahman1

Preeti Jain1 and Hasan Mahmud Reza1

1Department of Pharmaceutical Sciences North South University Dhaka 1229 Bangladesh2Department of Pharmacy Stamford University Bangladesh Dhaka 1217 Bangladesh3School of Biomedical Sciences Charles Sturt University Wagga Wagga NSW 2678 Australia

Correspondence should be addressed to Md Ashraful Alam sonaliagunyahoocom andHasan Mahmud Reza rezanorthsouthedu

Received 30 August 2014 Accepted 5 December 2014

Academic Editor Xian-Cheng Jiang

Copyright copy 2015 Md Ashraful Alam 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 is properlycited

Diabetes obesity and metabolic syndrome are becoming epidemic both in developed and developing countries in recent yearsComplementary and alternative medicines have been used since ancient era for the treatment of diabetes and cardiovasculardiseases Bitter melon is widely used as vegetables in daily food in Bangladesh and several other countries in Asia The fruitsextract of bitter melon showed strong antioxidant and hypoglycemic activities in experimental condition both in vivo and in vitroRecent scientific evaluation of this plant extracts also showed potential therapeutic benefit in diabetes and obesity relatedmetabolicdysfunction in experimental animals and clinical studies These beneficial effects are mediated probably by inducing lipid and fatmetabolizing gene expression and increasing the function of AMPK and PPARs and so forth This review will thus focus on therecent findings on beneficial effect of Momordica charantia extracts on metabolic syndrome and discuss its potential mechanismof actions

1 Introduction

The prevalence of obesity is increasing at an alarming rateand has become one of the worldrsquos most serious publichealth problems It has been estimated that 58 of worldpopulation will become obese by 2030 [1] Global surveydata also indicate that the prevalence of both male andfemale overweight and obesity varies by region and hasrapidly increased in recent years [2 3] Elements that causeobesity involve metabolism several genetic factors diet andphysical activity as well as the sociocultural surroundingsthat characterize the modern day living [4] Recent evidencessuggest that high fat diet which is also characteristic ofcafeteria type diet as well as sedentary life style are twocontributory factors for increased trends of obese peopleamong the nations [5] However genetic factors contributeto the variation of adiposity in approximately 40ndash70 of a

population [6] These genetic factors thus explain the failureof exercise and dietary regime to bring about long-termweight loss in some individuals Obesity can be defined asincreased energy intake than energy expenditure which ulti-mately results in fat deposition and weight gain Accordingto guidelines from the World Health Organization (WHO)overweight in adults is defined by body mass index (BMI)of 250 to 299 and obesity is defined by a BMI of 300or higher [7] High body fat increases the risk of severaldiseases such as diabetes hyperlipidemia and hypertensionwhich may lead to arteriosclerotic disease and metabolicsyndrome [8] Consequently obesity and related cardiovas-cular complications are also increasing alarmingly both indeveloped and developing countries Adipocyte dysfunctionand inflammation contribute to the various complicationsassociated with obesity Recently adipose tissues are con-sidered as an endocrine organ which secretes numerous fat

Hindawi Publishing CorporationJournal of LipidsVolume 2015 Article ID 496169 18 pageshttpdxdoiorg1011552015496169

2 Journal of Lipids

and glucose regulating hormones adipokines and cytokineslike adiponectin leptin and tumor necrosis factor-120572 (TNF-120572) [9 10] Increased concentration and expression of TNF-120572interleukin-6 (IL-6) andmonocyte chemoattractant protein-1 (MCP-1) are evident in adipocyte dysfunction and insulinresistance [11] Furthermore inflammatory cells such asmacrophages infiltration are also increased in adipose tissues[12] Proinflammatory cytokines and oxidative stress havealso been shown to be responsible for developing metabolicdisturbances such as insulin resistance and activation ofimmune response in liver adipose tissue and muscle [13ndash15] Moreover activation of inflammatory pathways in hep-atocytes is sufficient to cause both local as well as systemicinsulin resistance [16 17]

In the last decade much attention has been focusedon several molecular drug targets with the potential toprevent or treat metabolic disorders Thus nuclear receptorsand their regulators have attracted much attention dueto their regulatory role in both glucose homeostasis andlipogenesis [18] Peroxisome proliferator-activated receptors(PPARs) and liver X receptors (LXRs) are two regulatoryproteins identified to play a pivotal role in the regulationof metabolic homeostasis [19ndash21] while PPARs activationis important for lipid metabolism adipocyte differentiationand the prevention of inflammation [22] PPARs also regu-late mitochondrial biogenesis via an activator called PGC-1120572 [23 24] which is physiologically regulated by exercise[25 26] and calorie restriction [27] In addition to thesefactors pharmacological agents such as fenofibrates [28]and resveratrol [29] may also stimulate PGC-1120572 and restoremitochondrial function Recent reports suggest that naturalproducts are rich source of ligands for nuclear receptorsand are promising therapeutic agents in clinical practiceResearchers have also examined the effects of various func-tional foods on overall body composition and selective fatdepots Water-soluble extract of Cucurbita moschata stem(500mgkgday for 8 weeks) activated PPAR-120572 increased120573-oxidation and inhibited adipocyte differentiation in adose dependent manner [30] Extracts of Euonymus alatusincreased the expression of PPAR-120574 in periepididymal fatpad and ameliorated the hyperglycemia and hyperlipidemiainduced by high-fat diet in vivo [31] Acacia polyphenolsincreased the mRNA expression of fat metabolizing geneslike PPAR-120572 and PPAR-120575 in skeletal muscle and loweredthe expression of fat acid synthesis-related genes (SREBP-1cACC and FAS) in the liver [32] Green tea catechins have alsobeen proposed as therapeutic agents for body fat reduction[33]

Bitter melon (Momordica charantia L) is widely used forthe treatment of diabetes Recent research reports suggest thatbitter melon extracts may ameliorate high fat diet inducedobesity and hyperlipidemia in animal model Most findingsrelated to obesity and hyperlipidemia also showed that theplant extracts may modulate fat metabolizing kinases suchas AMPKs genes and nuclear factors like PPARs LXRs andPGC-1120572 in liver and skeletal muscle and affected adipocytedifferentiationwhile several reviewpapers suggest the antidi-abetic mechanism [34] and various pharmaceutical effects ofthe plant [35] and emphasized its efficacy and safety aspects

Figure 1 Fruits of different variety ofMomordica charantia availablein Bangladesh Upper left one is commonly known as Korolla andright one as Ucche

Therefore the present review aims to describe the effect ofbitter melon extracts on various parameters of metabolicsyndrome obesity and related cardiovascular complicationsMoreover this review will also find out the plausible mech-anisms responsible for antiobesity and hypolipidemic effectsof the plant based on available information to date

2 Bitter Melon Overview and TraditionalMedicinal Uses

Bitter melon is a climbing shrub cultivated mainly inBangladesh India China and Korea mostly in Asian coun-tries The plant also grows in tropical areas of Amazon EastAfrica and the Caribbean It belongs to family Cucurbitaceaeand the scientific name is Momordica charantia Generallytwo varieties of the plant are found in Bangladesh while thesmall size one is locally called ldquoUccherdquo and the large sizeone is locally known as ldquoKorollardquo (Figure 1) However someother wild type African species are also found in the countrythat include M balsamina L M foetida Schum and Mrostrata A Zimm Bitter melon fruits are taken as culinaryvegetable in Bangladesh and in Indian subcontinent it is alsoused as a traditional medicinal plant for the treatment ofvarious diseases in Bangladesh as well as other developingcountries like Brazil China Colombia Cuba Ghana HaitiIndia Mexico Malaya Nicaragua Panama and Peru [35]Perhaps the most common traditional use of the plant isto treat diabetes in different countries around the globe Itis also used for the treatment of various other pathologicalconditions such as dysmenorrhea eczema emmenagoguegalactagogue gout jaundice kidney (stone) leprosy leucor-rhea piles pneumonia psoriasis rheumatism and scabies[35] Momordica charantia are also documented to possessabortifacient anthelmintic contraceptive antimalarial andlaxative properties [35]

Recent scientific exploration on this plant elucidatedpotential biological effect on both animal and clinical studiesApart from its potential antibacterial [36] and antiviral activi-ties [37] bittermelon extracts are also effective against cancerand were found to be effective for the treatment of ulcermalaria pain and inflammation psoriasis dyslipidemia andhypertensionMomordica charantia also contains biologicallyactive chemical compounds such as glycosides saponins

Journal of Lipids 3

alkaloids fixed oils triterpenes proteins and steroids [38]Several other biologically active chemical constituents haveso far been isolated fromdifferent parts of the plant includingthe leaves fruit pulp and seeds

Typical Recipe of a Bitter Melon Dish Popular in Bangladesh

Bitter Melon Fry with Potato Ingredients are as follows

bitter melon (finely chopped) 100 gpotato (finely chopped) 1-2 (whole potato)onion 1 full (finely chopped)garlic paste half table spoonhot chilli 2 piecescurcuma powder half table spoonoil (soyabean) 1-2 table spoon fullsalt (qst)

First fry the chopped onion garlic and chilli togetherwith soyabean oil in a cocking pan Add some curcumapowder and salt and fry gently After finishing this stage addchopped bitter melon and potato in fried onion and fry untilthe potato andmelon get brown color on its surface and a nicesmell will come out from the dish Serve it with warm riceor paratha bread made up of flour having layers and fried invegetable oil

3 Chemical Constituents Isolated fromBitter Melon

M charantia contains a number of chemical substancesincluding nutritionally important vitamins minerals antiox-idants and many other phytochemicals that is glycosidessaponins phenolic constituents fixed oils alkaloids reducingsugars resins and free acids [35] The immature fruits arealso good source of vitamin C and also provide vitamin Aphosphorus and iron [35] Depending on the characteristicsnature of the isolated compounds they can be divided intoseveral groups such as phenolic and flavonoid compoundscucurbitane type triterpenoids cucurbitane type triterpeneglycoside oleanane type triterpene saponins and insulin likepeptides

31 Phenolic and Flavonoids Compounds Phenolic com-pounds isolated from M charantia are gallic acid tannicacid (+)-catechin caffeic acid p-coumaric gentisic acidchlorogenic acid and epicatechin [39ndash41] Figure 2 illustratesthe phenolic constituents which have been isolated from Mcharantia using high performance liquid chromatography(HPLC) analysis

32 Cucurbitane Type Triterpenoids The terpenoids are iso-prenoids derived from five carbon isoprene units The cucur-bitacins are a typical group of cucurbitane type triterpenoidsfoundmainly in cucumber family (Cucurbitaceae)Themainchemical constituents of M charantia are cucurbitane typetriterpenoids [42ndash44] including charantin [45] different

OHOH

H H

COOH

OMe

OH

H H

COOH

OHOH

COOH

HO

HO

O

OH O

OH

OH

OH

OH

HO

Caffeic acid Ferulic acid Gallic acid

p-coumaric acid (+)-catechin acid

Figure 2 Different phenolic compounds isolated from M charan-tia

kuguacins [46] momordicin and karavilagenins [47] Fig-ure 3 represents the chemical structures of the triterpenoidsfound in the plant

33 Cucurbitane Type Triterpene Glycoside Cucurbitane gly-cosides isolated from M charantia are charantosides IndashVIII[48] momordicosides F1 F2 G I K L M N O Q R Sand T [49ndash51] karavilosides I II III IV V VI VII VIII IXX and XI [47] Other cucurbitane type triterpene glycosidesinclude 3-O-120573-D-allopyranosyl 7120573 25-dihydroxycucurbita-5 and 23(E)-diene-19-al [52] 3-O-120573-D-allopyranosyl 7120573 25-dihydroxy cucurbita-5(6) 23(E)-diene-19-al 3-O-120573-D-allopyranosyl 25-methoxy cucurbita-5(6) and 23(E)- diene-19-ol [53] goyaglycoside-a -b -c -d -e -f -g and -h [54]Cao et al recently isolated and identified new cucurbi-tane triterpenes 512057319-epoxy-cucurbita-622E24-trien-3120573-ol from acid-treated ethanol extract of the plant [55]

Cucurbitane type triterpinoid glycosides which are abun-dantly present in Momordica genus and have been isolatedfromM charantia are presented in Figure 4

34 Oleanane Type Triterpene Saponins Several oleananetype triterpene saponins such as soyasaponins I II andIII have been isolated from the fresh fruit of Japanese MCharantia [56]

35 Peptides Recently two novel peptides MCh-1 andMCh-2 have been isolated from the seeds of bitter melon [57]

4 Effect of Bitter Melon on Body WeightObesity and Adipocyte Dysfunction

Body weight gain and abdominal fat deposition are theearly signs of obesity Bitter melon extract showed usefulbenefit on body weight gain and fat deposition (Figure 5Table 1) Several investigational reports suggest that bittermelon can reduce body weight in high fat diet inducedobesity in laboratory animals Bitter melon (075 of diet)

4 Journal of Lipids

Kuguacin AHO

OHOHC

OHO

OH

O

Kuguacin B Kuguacin C

HO O

O

HO

OHC

O

O

Kuguacin D

HO O

O

O

Kuguacin E Kuguacin F

OHC

O

O

O

O

OHC

O

O

O

O

OH

Kuguacin G

O-glucoseCharantin

CH(CH3)2

H3C

OHC

O

O

O

OH

Kuguacin HO

O

OO

OMe

Kuguacin I

OHC

OHHO

Kuguacin J

COOH

OHC

OOO

Kuguacin K

OO

OO

Kuguacin M

OHC

OHHO

O

Kuguacin N

OHC

OO

O

Kuguacin O

Kuguacin P

O

O

OO

HH

O

O

OO

OEtH

Kuguacin Q

HOO

HHO

OH

Kuguacin R

OHC

O

OH

O

Kuguacin S

OHC

HO OH

OH

Momordicine I

HO

OMe

OMe

Karavilagenin A

HO

OH

OMe

Karavilagenin B

HO OMe

Karavilagenin C

Kuguacin L

OO

O

CH2OH

H

Figure 3 Chemical structure of some cucurbitane triterpenoids isolated fromM charantia

supplementation prevented the body weight gain and visceralfat mass significantly in rats fed high fat diet [58] Thisweight reduction may be a result of increased fatty acidoxidation which ultimately facilitates weight reduction [58]

Moreover the bitter melon extract supplementation reducedthe peritoneal fat deposition in rats fed a high fat diet [58]In another study bitter melon significantly decreased theweights of epididymal white adipose tissue (WAT) visceral

Journal of Lipids 5

RO

O

HH

RO

O

HH OMe

OMe

OMe

OH

O

MeOCOOH

OHOH

1516-Dihydroxy-alpha-eleostearic acid

OH

OH

OH

OH

H

OR

Momordicoside A

Momordicoside BGlu-pyr

Xyl-pyr

R = 120573-gentiobiosyl

R = -Glu-pyr

OHOH

OH

H

Momordicoside C

120573-gentiobiosyl-O

CHOH

Momordicoside E


OHH

OH

Momordicoside D


O

HH

OMe

Charantosides I120573-D-glucopyranosyl-O

O

HHOMe OMe

Charantosides II120573-D-allopyranosyl-O

HO

OROHC

120573-D-glucopyranosyl

Momordicoside K R = MeMomordicoside L R = H

O

Momordicoside F1R1 = Me R2 = 120573-D-glucopyranosylMomordicoside F2R1 = H R2 = 120573-D-allopyranosylMomordicoside GR1 = Me R2 = 120573-D-allopyranosylMomordicoside I R1 = H R2 = 120573-D-glucopyranosyl

OR1

R2O

R2O

OR1

OR1

OR1

R2O R2O

Charantosides IIIR = 120573-D-glucopyranosylCharantosides IVR = 120573-D-allopyranosyl

Charantosides VR = 120573-D-glucopyranosylCharantosides VIR = 120573-D-allopyranosyl

Karaviloside IR1 = Me R2 = 120573-D-glucopyranosylKaraviloside IIR1 = Me R2 = 120573-D-allopyranosylKaraviloside IIIR1 = H R2 = 120573-D-allopyranosyl

Karaviloside IVR1 = 120573-D-glucopyranosyl R2 = HKaraviloside VR1 = 120573-D-allopyranosylR2 = 120573-D-allopyranosyl

Goyaglycoside-aR1 = H R2 = 120573-D-glucopyranosylGoyaglycoside-bR1 = H R2 = 120573-D-allopyranosylGoyaglycoside-cR1 = Me R2 = 120573-D-glucopyranosylGoyaglycoside-dR1 = Me R2 = 120573-D-allopyranosyl

Figure 4 Chemical structure of major cucurbitane glycosides isolated fromM charantia

6 Journal of Lipids

Table 1 Effect of bitter melon on body weight obesity and adipocyte dysfunction

Model Dose Experimental outcome ReferenceHF diet induced fatrats

075 and 15extracts

(i) Decreased body weight visceral fat mass plasma glucose and TAG(ii) Increased plasma catecholamines [58]

HF diet induced fatrats

075 and 15extracts

(i) Decreased body weight visceral fat mass plasma glucose and TAG(ii) Increased adiponectin(iii) Increased UCP 1 in BAT and UCP 3 in red gastrocnemius muscle(iv) Increased expression of the transcription coactivator PGC-1120572 both in BAT andin gastrocnemius muscle

[62]

Male C57BL6Jmice 5 weeks old

05 gkgday10 gkgday Pextracts or 0210 gkgday G

extracts

(i) Decreased body weight and visceral fat mass(ii) Decreased plasma glucose TG and total cholesterol (TC) but increased freefatty acid (FFA)(iii) Increased mRNA expression of leptin PPAR-120574 PPAR-120572 and decreasedexpression of resistin

[59]

Male Wistar ratsfed HF diet 5 (ww) powder

(i) Decreased body weight and adipose tissues(ii) Decreased TAG and cholesterol(iii) Increased adiponectin

[63]

Over weight rats Aqueous extract2mLday

(i) Reduced elevated body weight and cholesterol TG and low-density lipoproteincholesterol (LDL-C)(ii) Increased high density lipoprotein cholesterol (HDL-C)

[60]

HF diet fed maleC57BL6JNarlmice

15 and 30 of diet

(i) Decreased body weight retroperitoneal epididymal and inguinal fat depositionand adipocyte diameter(ii) Increased phosphorylation of acetyl-CoA carboxylase cAMP-activated proteinkinase (PKA) and signal transducer and activator of transcription 3 in WAT(iii) Increased TNF-120572 concentration in the WAT accompanied by TUNEL-positivenuclei

[61]

3T3-L1 cells (i) Decreased lipid accumulation and intracellular TGs [64]

Primary humanadipocyte

(i) Inhibited adipocyte differentiation by reducing PPAR120574 SREBP and perilipinmRNA gene expression(ii) Increasing lipolysis in preadipocytes

[65]

fat and the adipose leptin and resistin mRNA levels inC57BL6J mice fed with a high-fat (HF) diet [59] Bano etal reported that 2mLday dose of aqueous extract of bittermelon significantly reduced body weight gain in rats [60] Arecent study also showed that the seed oil supplementation ofthe plant reduced body weight and fat mass inmice fed a highfat diet [61]

Several mechanisms for lowering fat mass in obesityhave been proposed Generally increased fatty acid transportwould facilitate fat burning in tissues Carnitine palmitoyl-transferase (CPT) system is the predominant system fortransporting the fatty acid to mitochondrial matrix [83] TwoCPTswere identified so far CPT-1 andCPT-2 and a carnitineCPT-1 resides on the inner surface of the outermitochondrialmembrane and is a major site of regulation of mitochondrialfatty acid uptake It is evident that obesitymay reduce the lipidoxidation in skeletal muscle due to the reduced expressionand activity of CPT system in human and animal [84]Earlier investigations also suggest that inhibition of CPT-1with the chemical etomoxir increases lipid deposition andexacerbates insulin resistance when animals are placed ona HF diet [85] whereas overexpression of CPT-1 improvedlipid-induced insulin resistance [86] Additionally increasedskeletal muscle CPT-1 protein expression is sufficient toincrease fatty acid oxidation and to prevent HF diet-inducedfatty acid esterification into intracellular lipids subsequently

leading to enhanced muscle insulin sensitivity in HF-fed rats[87] Bitter melon supplementation in these rats significantlydecreased the body weight gain by increasing the hepatic andmusclemitochondrial carnitine palmitoyltransferase-I (CPT-1) and acyl-CoA dehydrogenase enzyme [62]

Mitochondrial uncoupling is another process in mito-chondria whereby most of the energy consumed will beconverted into heat rather than producing ATP The pro-ton gradient generated for the ATP synthesis is consumedthrough specified protein function known as uncouplingproteinswhich are attaining interest in recent years because oftheir critical role in energy expenditure and lipid metabolism[88] Several uncoupling proteins have been isolated thatis UCP1 UCP2 UCP3 UCP4 and UCP5 These proteinsare distinctively expressed in several tissues and primarilyparticipate in proton leaking Alteration in function of theseproteins will be beneficial in weight reduction in obesity[88] In mice genetic manipulation of UCP3 in skeletalmuscle suggests that this protein is involved in the regulationof energy expenditure [89] UCP1 in brown adipose tissue(BAT) andUCP3 in red gastrocnemiusmusclewere increaseddue to bitter melon supplementation followed by increasedexpression of the transcription co-activator PGC-1120572 a keyregulator of lipid oxidation [62]

Adipose tissues also play a central role in obesity Bittermelon supplementation prevented the adipocyte hypertrophy

Journal of Lipids 7

Liver

- Increased PPAR-120572 and PPAR-120574 expression- Increased expression of the transcription

coactivator PGC-1120572- Increased 120573-oxidation- Decreased fatty acid synthesis- Decreased fat

Pancreas

- Increased insulin secretion- Prevents 120573-cell damage- Increased PPAR-120572 and PPAR-120574

expression in skeletal muscle

Fat cells

- Inhibited adipocyte hypertrophy- Inhibited adipocyte differentiation- Increased PPAR-120574 expression- Increased expression of the

transcription coactivator PGC-1120572- Decreased visceral fat mass

Figure 5 Effect of bitter melon on various organ and probable molecular targets for improving obesity and diabetes

in rats fed HF diet [63] Its supplementation suppressed thevisceral fat accumulation and inhibited adipocyte hypertro-phy probably by lowering mRNA levels of fatty acid synthaseacetyl-CoA carboxylase-1 lipoprotein lipase and adipocytefatty acid-binding protein downregulating lipogenic genesin adipose tissues [63] A recent study suggests that bittermelon seed oil may increase the adipocyte death by cAMP-activated protein kinase (PKA) mediated apoptosis in whiteadipose tissues (WAT) of HF diet fed mice [61] Previous invitro study also showed prevention of preadipocyte differ-entiation and lipid accumulation in adipocyte by the plantextract Bitter melon treatment of 3T3-L1 cells resulted ina decreased lipid accumulation and significantly decreasedintracellular triglyceride (TG) amount compared to untreatedcontrol cells [64] Moreover bitter melon reduced the lipidaccumulation during differentiation from a preadipocyteto adipocyte and downregulated PPAR120574 [64] PPAR120574 isconsidered the master regulator of adipogenesis during dif-ferentiation of preadipocyte to adipocyte [90] Other adi-pogenic transcription factors include the CCAATenhancerbinding proteins (CEBP120572 CEBP120573 and CEBP120575) and sterolregulatory element-binding protein 1c (SREBP-1c) [91] Bittermelon juice inhibited adipocyte differentiation by reducingPPAR120574 SREBP and perilipin mRNA gene expression and byincreasing lipolysis in primary human adipocyte [65]

5 Effect of Bitter Melon on Dyslipidemia

Dyslipidemia are disorders related to increased cholesterolsynthesis and abnormal lipoprotein metabolism includinglipoprotein overproduction and deficiency which are theearly manifestations of obesity Plasma lipids such as choles-terol fatty acids and TG concentrations are increased due todiabetes andHF diet feeding in laboratory animal and human[92] Dyslipidemia is widely accepted as independent riskfactor for coronary heart disease and associated with insulin

resistance in type 2 diabetes mellitus [93] The main causeof increased cholesterol and TGs in diabetic dyslipidemia isthe increased FFA release from insulin-resistant fat cells [94]Thus FFAs overload into the liver and increased glycogenstores promote TG production which in turn stimulatesthe secretion of apolipoprotein B (ApoB) and very low-density lipoprotein (VLDL) cholesterol [93 94] The hepaticoverproduction of VLDL appears to be the primary andcrucial defect of the insulin resistant accompanying obesity

Bitter melon extracts showed lipid lowering effect bothin diabetic and HF diet fed rats (Table 2) Bitter melonexhibited a marked reduction in the hepatic TC and TGin dietary cholesterol fed rats [66] However the bittermelon extract showed little effect on serum lipid parametersbut increased HDL-C both in the presence and absence ofdietary cholesterol in rats [66] Ahmed et al reported that10 weeks of supplementation of the plant extract normalizedthe increased plasma nonesterified cholesterol TGs andphospholipids in streptozotocin- (STZ-) induced diabeticrats [67] Treatment for 30 days with Momordica charantiafruit extract to diabetic rats also decreased TG and LDLand increased HDL level significantly [68] Chen and Li alsoreported that 075 bitter melon extracts supplementationreduced the plasma cholesterol in rats fed a HF diet [58]Another study showed that bittermelon reducedTG and LDLlevels and increased HDL levels in high sucrose fed rats [71]Ground bitter melon seeds (30 wtwt) decreased TC andLDL-C and increased HDL-C in female Zucker rats [73] Theplant supplementation also decreased plasma level of TGcholesterol and FFA in plasma of offspring rats fed a HFdiet [72] Oishi et al reported that saponin fraction of theplant decreased the TAGand pancreatic lipase activity in cornoil loaded rats [69] Decreased pancreatic lipase activity isparticularly important in fat absorption from gut wall as itenhances the fat digestion to fatty acids and increased plasma

8 Journal of Lipids

Table 2 Effect of bitter melon extracts on lipid parameters of diabetic and obese animal models

Model Dose Experimental outcome Reference

Cholesterol fed rats 05 1 and 3 of diet (i) Not changed TC level but(ii) increased HDL-C level in plasma [66]

STZ-induceddiabetic rats

10mL 100 fruitextract per kg bodyweight daily for 10

weeks

(i) Decreased elevated level of plasma cholesterol TGs and phospholipids in STZinduced diabetic rats [67]

Diabetic rats (i) Decreased in TG and LDL(ii) Increased in HDL [68]

Rats fed a HF diet 75 gkg or 075

(i) Supplementation did not affect serum and hepatic cholesterol(ii) Supplementation in HF diet rats led to a lowering of hepatic TAG and steatosisscore in liver section(iii) Plasma epinephrine and serum FFA concentrations were increased(iv) Lowered TAG concentration in red gastrocnemius and tibialis anterior

[58]

Wistar ratsSaponin fraction

(50ndash100mgkg bodyweight)

(i) Decreased pancreatic lipase activity and serum TG level in corn oil loaded rats [69]

Female C57BL6mice fed with HFdiet

15 freeze-dried BMJwith diet

(i) Normalized plasma TAG cholesterol and NEFA(ii) Normalized AST ALT and ALP in plasma(iii) Decreased ApoB secretion and modulated the phosphorylation status of IR andits downstream signalling molecules

[70]

Albino rats fedwith sucrose

40 80 and 120mgkgof body weight

(i) Reduced TG and LDL levels and increased HDL levels(ii) Normalized hyperglycemia(iii) Lowered TBARS and normalized levels of reduced glutathione

[71]

Offspring rats fedhigh (60)fructose diet

1 of diet

(i) Decreased plasma level of TG cholesterol and FFA(ii) Lowered the hepatic levels of stearoyl-CoA desaturase and microsomal TGtransfer protein mRNA(iii) Increased PPAR120574 coactivator 1-120572 and fibroblast growth factor 21 mRNA andfatty acid binding protein 1

[72]

Female Zucker rats 30 (wt = wt)ground BMS

(i) Supplementation increased the expression of PPAR-120574 in the WAT(ii) Decreased TC and LDL-C increased HDL-C(iii) Downregulated the expression of PPAR-120574 nuclear factor-kB (NF-kB) andinterferon-120574mRNA in heart tissue

[73]

HF diet fed mice 12 plant extract

(i) Decreased TC TGs and LDL-C(ii) Increased hepatic AMPK p AMPK 1205721 AMPK 1205722 and Sirt1 content(iii) FGF21 and insulin concentrations were significantly decreased(iv) Hepatic FGF21 content was significantly downregulated while FGF receptors 13 and 4 (FGFR1 FGFR3 and FGFR4) were greatly upregulated

[74]

Wistar rats fedhigh cholesteroldiet

(i) Decreased serum TC and LDL-C HDL-C(ii) Decreased mRNA levels of hepatic LXR120572 in rats(iii) Increased the hepatic CYP7A1 mRNA level

[75]

C57BL6J mice45 HF diet

01 02 and04 gkgday extracts

(i) Decreased serum TC and fatty acids(ii) Normalized leptin and insulin concentration(iii) Increased PPAR120572 level in liver(iv) Increased GLUT4 expression in skeletal muscle(v) Significantly increased the hepatic protein contents of AMPK phosphorylationand decreased expression of phosphoenolpyruvate carboxykinase (PEPCK)

[76]

fatty acid level after fat intake Thus reduction of pancreaticlipase would be a crucial target for lowering circulating FFAs

The molecular mechanisms behind the lipid loweringeffect of bitter melon extracts are revealed only recentlyFreeze-dried bitter melon juice (15) with diet normalizedplasma TAG cholesterol and NEFA in female C57BL6 micefed aHFdiet [70] In this study the juice in diet also decreasedApoB secretion andmodulated the phosphorylation status ofinsulin receptor (IR) and its downstream signallingmolecules

[70] Insulin resistance and dyslipidemia are characterizedby significant downregulation of hepatic insulin signallingas documented by attenuated phosphorylation of IR andIR substrates (IRS) [95] A direct link between attenuatedhepatic insulin signalling and synthesis and secretion ofVLDL apoB was established before [96] VLDL particlesare mainly cleared from circulation by the LDL receptor(LDLR) also referred to as apoBE receptorThe transcriptionof the LDLR gene is regulated by intracellular cholesterol

Journal of Lipids 9

concentration hormones and growth factors Moreoversterol regulatory element binding protein-1 (SREBP-1) isselectively involved in the signal transduction pathway ofinsulin and insulin-like growth factor-I (IGF-I) leading toLDLR gene activation contributing to the delayed VLDLparticle clearance associated with obesity causing insulinresistance [97] Transcription factors in the SREBP family arekey regulators of the lipogenic genes in the liver

Increased mitochondrial biogenesis would be a possibleway of increasing lipid metabolism and utilization in energydemanding cells and tissues Mitochondrial biogenesis isregulated via several transcriptional regulatory factors likeAMPK PPAR-120574 and PGC-1120572 [98 99] AMPK regulatedPPAR-120574 and PGC-1120572 activation stimulated most of thetranscriptional signal to increase fatty acid oxidation andmitochondrial function [100ndash102] Bitter melon supplemen-tation increased PPAR120574 coactivator 1-120572 (PGC 1 120572) andfibroblast growth factor 21 mRNA and fatty acid bindingprotein 1 in offspring of HF diet fed rats [72] PGC-1 familyof coactivator is of particular importance in the controlof liver metabolism [98] PGC-1120572 stimulates mitochondrialbiogenesis and respiration in multiple cell types and modu-lates biological programs normally associated with increasedoxidative metabolism [103] This PGC-1120572 activation andupregulation by bitter melon supplementation also decreasedplasma level of TGs cholesterol and FFA in plasma ofoffspring rats fed a HF diet [72] Recent investigation alsoreported that 12 bitter melon extract supplementationsignificantly increased hepatic AMPK p AMPK 1205721 AMPK1205722 and Sirt1 content in HF diet fedmice [74] AMP-activatedprotein kinase (AMPK) is a cellular fuel gauge maintainingintracellular energy balance inmammalian cells [104] AMPKactivation is necessary for the transcriptional regulation ofenergy demand Mice expressing a dominant-negative formof AMPK failed to increase mitochondrial biogenesis inresponse to energy deprivation in skeletal muscles [105]In contrast lipid oxidation and mitochondrial activity wereincreased inmice over expressing the phosphorylated AMPK[106 107] Thus AMPK activation followed by Sirt1 dueto the plant extract supplementation decreased TC TGsand LDL-Cin HF diet fed mice [74] Bitter melon extractsupplementation also decreased serum TC and fatty acidsin C57BL6J mice 45 high-fat (HF) diet [76] This lipidlowering effect is attributed to its ability to increase AMPKphosphorylation and PPAR120574 mediated lipid metabolism inliver [76]

The plant extract supplementation also decreased mRNAlevels of hepatic LXR120572 and increased the hepatic CYP7A1mRNA level in rats [75] LXRs were first identified asorphan members of the nuclear receptor super family andoxidized derivatives of cholesterol act as ligands for the LXRsLXR also plays an important role in lipid and cholesterolmetabolism LXR120572 knockout mice develop enlarged fattylivers degeneration of liver cells high cholesterol levels inliver and impaired liver function when fed a high-cholesteroldiet [108] Hepatic LXR120572 downregulation due to bitter melonextract supplementation also decreased serum TC and LDL-C HDL-C in Wistar rats fed high cholesterol diet [75]

6 Effect of Bitter Melon on Nonalcoholic FattyLiver and Liver Diseases

Hepatoprotective effect of bitter melon extracts is mainlyattributed to its antioxidant capacity to scavenge free radicalsand reduced inflammation in liver due to noxious stimuliChaudhari et al reported that hydroalcoholic extract of theplant leaves (100 and 200mgkg) normalized the levels ofALT AST ALP and total bilirubin and prevented steatosiscentrilobular necrosis and vacuolization in liver of carbontetrachloride induced liver damage in rats [109] ALT ASTand ALP are liver enzymes that significantly increased dueto increased metabolism or damage to the liver tissuesThe study by Thenmozhi and Subramanian also confirmedthe antioxidant and hepatoprotective potential of its fruitextract in ammonium chloride-induced toxicity in rats [110]Fruit extract (300mgkg) of the plant normalized the ele-vated TBARS hydroperoxides and liver markers (alaninetransaminase ALT aspartate transaminase AST and alka-line phosphatase ALP) and increased the levels of glutathioneperoxidase (GPx) superoxide dismutase (SOD) and catalaseand reduced glutathione in ammonium chloride-inducedtoxicity in rats [110] The plant extract at a dose of 5mLkgalso produced significant protection of liver damage due tohigh dose of acetaminophen administration in rabbits [111] Arecent study also suggests that bitter melon supplementationameliorates oxidative stress in liver of fructose fed offspringof rats by improving the antioxidant enzymes activity such asGPx SOD and catalase [112]

Liver is the first line organ which undergoes direct chal-lenges during diet induced obesity and diabetes Excess fatintake overwhelms the hepatic tissues tometabolize themandundergoes fatty acid mediated inflammation and oxidativestress [113] Excess fat accumulation in liver can be a result ofone or a combination of the following metabolic alterations(a) decreased 120573-oxidation of fatty acids (b) increased fattyacid synthesis due to up-regulation of lipogenic pathways(c) increased delivery of fatty acids from adipose and otherorgans due to lipolysis and (d) inhibition ofVLDL-TG export[114] Numerous studies indicated that high fat and fructoseoverconsumption leads to the development of metabolicsyndrome including insulin resistance dyslipidemia andhypertension in humans [115 116] and animals [113 117]High fat diet also develops hepatic steatosis in animal byaccumulating lipid in hepatic tissues [113] Bitter melonsupplementation reduced the fat accumulation in liver andprevented steatosis inmice fed a high fat diet [74] In thismicemodel high fat diet feeding caused upregulation of fibroblastgrowth factor 21 levels in liver [74] FGF family plays valuablerole in the development of NAFLD [118] It has been shownthat plasma FGF21 levels were increased in patients withinsulin resistant type 2 diabetes mellitus (T2DM) and inNAFLD patients who have high level of hepatic triglycerides(TG) [118 119] The plant supplementation downregulatedhepatic FGF21 content significantly and increased hepaticphosphorylated AMPK AMPK 1205721 AMPK 1205722 and Sirt1content compared to the high fat diet fed mice [74]

10 Journal of Lipids

7 Effect of Bitter Melon on Diabetes

Mostly reported biological activities of bitter melon are theeffect on diabetes and hyperglycaemia The plant showedpotent antihyperglycemic effect in various animal modelsAn aqueous extract of bitter melon in normal mice loweredthe glycaemic response to both oral and intraperitonealglucose load without altering the insulin response [120]Aqueous and alkaline chloroform extracts also reduced thehyperglycaemia in diabetic mice [120] Pulp juice of thisplant lowered fasting blood glucose and glucose intolerancein NIDDM model rats while no effect was seen in STZtreated IDDM model rats [121] In alloxan induced diabeticrats blood sugar level was lowered after 3 weeks of treatmentwith aqueous extract of bitter melon fruits [122] The plantextract also improved glucose intolerance in STZ treateddiabetic rats and increased the glycogen synthesis in liver[123] The aqueous extract powder of fresh unripe wholefruits at a dose of 20 mgkg body weight reduced fastingblood glucose by 48 which is comparable to the effect ofglibenclamide a well-known oral antidiabetic drug in rats[124] Acute oral administrations of the whole plant extractalso caused dose-related significant hypoglycaemia in normal(normoglycaemic) and STZ-treated diabetic rats [125] Mcharantia extract also improved insulin sensitivity glucosetolerance and insulin signalling in high fat diet-inducedinsulin resistance rats [126]M charantia alsomaintained thenormal glucose concentration in chronic sucrose loaded rats[71]

Improvement of hyperglycaemic condition in experi-mental animal by M charantia extracts has many plausiblemechanisms that is (a) prevention of glucose absorption inthe alimentary canal (b) enhancing the glucose uptake bytissues (c) increasing glucosemetabolism and (d) enhancinginsulin like action and pancreatic beta cell stimulation [127]Oral administration of the plant juice significantly reducedthe Na+K+ - dependent absorption of glucose from theintestinal mucosa in STZ-induced diabetic rats [128] whichwere also observed in vitro [129] Moreover these extractsmay also inhibit carbohydrate metabolizing enzymes likealpha-amylase alpha-glucosidase and pancreatic lipase andhence limits the absorption of glucose through gut wall [130ndash132] Several authors reported that the plant extract improvesglucose uptake in cells thereby increasing the glucosemetabolism Oral supplementation of the plant increased themuscle content of facilitative glucose transporter isoform 4(GLUT4) proteins which might be responsible for significantimprovement of oral glucose tolerance in KK-Ay mice ananimal model with type 2 diabetes with hyperinsulinemia[133] Similar resultswere also reported by other investigatorsShih et al reported that bitter melon extract significantlyincreases the mRNA expression and GLUT4 in skeletalmuscle and normalized fructose diet-induced hyperglycemiain rats [134]

In vitro study suggested that the fresh juice of the plantincreased the uptake of amino acids and glucose in L6myotubes [135] Aqueous and chloroform extracts of thisfruit also increased glucose uptake and upregulated GLUT-4 PPAR-120574 and phosphatidylinositol-3 kinase (PI3K) in L6

myotubes [136] The effects of the plant on glucose uptakeand adiponectin secretion were also reported in adipose cells3T3-L1 adipocytes Water-soluble components of the plantenhanced the glucose uptake at suboptimal concentrations ofinsulin in 3T3-L1 adipocytes [137]

M charantia showed beneficial effect in diabetes bymaintaining normal glucose levels and several investigatorssuggested that this beneficial effect is attributed to its abilityto maintain the structural integrity of the pancreatic isletsand also by regulating its functions like synthesis and releaseof hormones [138ndash140] An investigation was carried outto observe the effect of Momordica charantia fruit juice onthe distribution and number of 120572 120573 and 120575 cells in thepancreas of STZ-induced diabetic rats and it was foundthat the juice significantly increased the number of 120573 cellscompared with untreated diabetic rats [138] However 120572-cells did not change significantly compared with untreateddiabetic rats in this study Oral administration of the seedextracts at a dosage of 150mgkg body weight for 30 daysprevented degeneration of pancreatic islets and restored isletsfunction [139] Acetone extract of the plant fruit powder atdoses 25 50 and 100mgkg body weight affected differentphases of recovery of 120573-cells of the islets of Langerhansand normalizes the functioning of the concerned cells [141]Moreover the fruit powder extracts enhanced neoformationof islets from preexisted islet cells along acinar tissues [141]A recent report also suggests that administration of ethanolicextract of the fruit pulp of the plant in neonatal STZ-induced type 2 diabetic rats increased the islet size total 120573-cell area number of 120573-cells and insulin levels compared withuntreated diabetic rats [140]

Other scientists also reported insulin secretagogue prop-erties of the plant as well Subcutaneous administration ofthe protein extract isolated from Momordica charantia fruitpulp increased plasma insulin concentrations by 2-fold after4 h of administration [142] The fruit pulp protein extractalso increased the insulin secretion but not glucagon inperfused rat pancreas [142] A recent report also suggeststhat saponin significantly stimulated insulin secretion in vitrofrom pancreatic MIN6 120573-cells [143]

Apart from these effects M charantia has also beenreported to improve the sensitivity of insulin in hyperin-sulinemia Bitter melon supplementation improved insulinresistance and lowered serum insulin and leptin to the highfat diet fed rats [144] It improves insulin sensitivity in skeletalmuscle by increasing skeletalmuscle insulin-stimulated IRS-1tyrosine phosphorylation in high-fat-fed rats [126] A recentreport further confirmed that polypeptide isolated from theplant binds with IRs and modulates downstream insulinsignalling pathways [145]

8 Effect of Bitter Melon on Hypertension andVascular Dysfunction

Hypertension and vascular dysfunction are two metabolicdisorders that occur during the progression of obesity andmetabolic syndrome and most of the obese people are

Journal of Lipids 11

Table 3 Clinical studies of bitter melon (MC)

Study design Subject Dose and duration Outcome Reference

Case study100 moderate noninsulindependent diabetic (NIDDM)subjects

Aqueous homogenizedsuspension of the vegetable pulp

Significant reduction of bothfasting and postprandial serumglucose levels was observed

[77]

Case study 15 patients of either sex (52ndash65years of age) of NIDDM

200mg twice dailywith 7 daystreatment plus half doses ofmetformin or glibenclamide orboth in combination

The extract acts in synergismwith oral hypoglycemics andpotentiates their hypoglycemia inNIDDM

[78]

Randomizeddouble-blindplacebo-controlledtrial

40 patients 18 years old andabove

Two capsules ofM charantiathree times a day after meals for3 months

No significant effect on meanfasting blood sugar totalcholesterol and weight or onserum creatinine ALT ASTsodium and potassium

[79]

Multicenterrandomizeddouble-blindactive-control trial

The total of 143 patients wereenrolled into the study 129patients were randomized to theeither metformin (119899 = 33) bittermelon 500mgday (119899 = 33)bitter melon 1000mgday(119899 = 32) or bitter melon2000mgday (119899 = 31)

Bitter melon 500mgday1000mgday and 2000mgday ormetformin 1000mgday for fourweeks

2000mgday dose showedsignificant decline infructosamine at week 4500 and 1000mgday did notsignificantly decreasefructosamine levels

[80]

Open-labeluncontrolledsupplementation trial

42 eligible (21 men and 21women) with a mean age of457plusmn 114 years (23 to 63 years)

48 gram lyophilized bitter melonpowder in capsules daily forthree months

The metabolic syndromeincidence rate decreasedcompared to that at baselineThe waist circumference alsosignificantly decreased after thesupplementation

[81]

Two-arm parallelrandomizeddouble-blindedplacebo-controlledtrial

19 type 2 diabetic patients takenfruit pulp and 19 type 2 diabeticpatients taken as placebo

6 gday of MC dried-fruit pulpcontaining 626plusmn 028mg ofcharantin

Significant decline of totaladvanced glycation end-products(AGEs) in serum after 16 weeksof the intervention

[82]

observed to developmoderate to high bloodpressureWhole-plant aqueous extract of the plant dose dependently normal-ized the hypertension in hypertensive Dahl salt-sensitive ratsprobably followed by acetylcholine mediated pathways [125]A recent investigation also showed thatM charantia extractslowered elevated blood pressure inWistar rats after L-NAMEchallenge on 52 days [146] Moreover the plant extracts alsoreduced the angiotensin converting enzyme activities [146]However frustrating results were also observed in clinicalsetup Recently a preliminary open-label uncontrolled sup-plementation trial was conducted in 42 people with a meanage of 457 plusmn 114 years who were supplemented with 48lyophilized encapsulated Momordica charantia powder dailyfor three months [147] But no significant differences werenoted in this study for high blood pressure heart rate andother parameters of metabolic syndrome [147]

9 Antioxidant Activity of Bitter Melon

Bitter melon showed potent antioxidant activities both invitro and in vivo as several investigators reported the antiox-idant activity of different parts of the plant from leavesto fruits Aqueous and methanolic extracts of bitter melonshowed increased metal chelating activity prevented lipid

peroxidation and inhibited free radical generation in xan-thine oxidase and cytochrome C mediated in vitro system[148] Aqueous extracts of leaves of the plant significantlyscavenge the DPPH free radicals and increased ferric reduc-ing power while fruits extracts scavenge hydroxyl radicalsand showed increased total antioxidant capacity [39] Phe-nolics extracted from pericarp and seed of the plant at threematurity stages also showed DPPH free radical scavengingactivity [149] Phenolic compounds isolated from the bittermelon are catechin gallic acid ferulic acid p-coumaric acidgentisic acid chlorogenic acid and epicatechin [39 149]

The antioxidant activity of the total aqueous extractand total phenolic extract of Momordica charantia fruitswas assessed in rat cardiac fibroblasts (RCFs) NIH 3T3and keratinocyte (A431) No significant cytoprotection wasobserved with both the extracts used in H

2O2and xan-

thine oxidase induced damages in cells [150] However theplant extracts showed significant protection against oxida-tive stress in several in vivo models Treatment with bittermelon extracts normalized the elevated concentrations ofTBARS hydroperoxides and liver markers (ALP AST ALT)in hyperammonemic rats induced by ammonium chloridewhile reversing the oxidant-antioxidant imbalance [110]Thisprotective effect is mediated probably by increasing the


AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS

ACCAcetyl CoA Malonyl CoA

Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus

Increased biogenesis

LXRsCell membrane

p

d

p

PGC1120572

Figure 6 Hypothetical mechanism of bitter melon on fat metabolism in liver tissue via AMPK-PPAR120574mediated pathways

activity and concentrations of GPx SOD and catalase andreduced glutathione in the liver and brain tissues [110] Theplant extracts also prevented the lipid peroxidation in chronicsucrose fed rats and normalized the reduced glutathione levelin liver [71]

10 Clinical Studies That Used Bitter Melon

Bitter melon extracts are considered the most popular tradi-tional medication used for the treatment of diabetes despiteits bitter taste Previous review report suggests that the clinicalstudies with bitter melon data with human subjects arelimited and flawed by poor study design and low statisticalpower [151] Table 3 summarized some important clinicalstudies that used various parts of bitter melon Ahmad etal reported that the aqueous homogenized suspension ofthe vegetable pulp significantly reduced both fasting andpostprandial serum glucose levels in noninsulin dependentdiabetic patients [77] However this study design was nota randomized placebo controlled study which lacks theappropriate comparison and biasness could not be excludedSimilar study was conducted by Tongia et al who reportedthat 200mg capsule of bitter melon twice daily synergisticallyimproved hypoglycemic action of metformin and gliben-clamide [78] Randomized double-blind placebo-controlledtrials with bitter melon are inconclusive and shortfall inappropriated study design patient number and duration ofstudy Fuangchan et al reported a decline of fructosaminelevel in diabetic patients at week 4 with 2000mgday dose

while other doses tested failed to show any significant effect[80] Tsai et al reported a decreased metabolic syndromeincidence rate compared to that at baseline and reductionof waist circumference in studied patients [81] Trakoon-osot et al also reported an improvement of diabetes con-dition in patients treated with bitter melon and a declineof advanced glycation end products (AGEs) in serum after16 weeks of the intervention were reported [82] Howeverother investigations reported by Dans et al showed thattwo capsules of bitter melon three times a day after mealsfor 3 months failed to produce any significant improvementin diabetic conditions [79] Almost all authors reported noserious side effects during the study period [152] In somepatients headache dizziness stomach pain and bloatingwere also reported

11 Summary and Future Prospective

To date M charantia has been extensively studied worldwidefor its medicinal properties to treat a number of diseaseslike diabetes dyslipidemia obesity and certain cancersIsolated compounds from this plant like charantin insulin-like peptide and alkaloid-like extracts possess hypoglycemicproperties similar to its crude extracts The plant and fruitextracts and different compounds seem to exert their benefi-cial effects via several mechanisms like AMPK PPARs LXRsSREBPs Sirts mediated glucose and fat metabolism in vari-ous tissues which are directly related to the beneficial effect ofcontrolling and treating diabetes mellitus dyslipidemia and


obesity related cardiovascular complications A hypotheticalmechanism has been proposed in Figure 6 which aimed toexplain the lipid lowering effect of bitter melon However aknowledge gap in research was observed in the field of anydirect effect of this plant on cardiac function hypertensionandhypercholesterolemia induced atherosclerosisMoreoverclinical studies reportedmostly lack appropriate study designand are inconclusive Thus further studies are required toconduct more double blind randomized trials with bittermelon extracts in diabetes patients as well as in obesepopulation Further researches are also advocated for elicitingthe effect of different dose of bitter melon in diabetic heartfailure and hypertension both in animal and in patients withdiabetes obesity and cardiovascular complications

Abbreviations

ACC Acetyl-CoA carboxylaseACE Angiotensin-converting enzymeALP Alkaline phosphataseAST Aspartate transaminaseALT Alanine aminotransferaseAMPK 51015840 AMP-activated protein kinase (51015840

adenosine monophosphate-activatedprotein kinase)

ApoB Apolipoprotein BBAT Brown adipose tissueBMI Body mass indexCEBP CEBPB CCAATenhancer binding

proteincAMP Cyclic adenosine monophosphate

(31015840-51015840-cyclic adenosinemonophosphate)

CPT-I Carnitine palmitoyltransferase ICYP7A1 Cholesterol 7 alpha-hydroxylase

(cytochrome P450 7A1)DPPH 22-Diphenyl-1-picrylhydrazylFAS Fatty acid synthaseFFA Free fatty acidFGF Fibroblast growth factorFGFR Fibroblast growth factor receptorGLUT4 Glucose transporter type 4HDL High-density lipoproteinHDL-C High-density lipoprotein cholesterolHF High fatHPLC High-performance liquid

chromatographyIDDM Insulin-dependent diabetes mellitusIGF Insulin-like growth factorIL-6 Interleukin 6IR Insulin receptorIRS-1 Insulin receptor substrate 1LDL Low-density lipoproteinLDL-C Low-density lipoprotein cholesterolLDLR Low density lipoprotein receptorL-NAME L-NG-nitroarginine methyl esterLXR Liver X receptorsMCP-1 Monocyte chemoattractant protein-1mRNA Messenger ribonucleic acid

NAFLD Nonalcoholic fatty liver diseaseNEFA Nonesterified fatty acidsNF-120581B Nuclear factor kappa-light-chain

enhancer of activated B cellsNIDDM Noninsulin-dependent diabetes mellitusPEPCK Phosphoenolpyruvate carboxykinasePGC Peroxisome proliferator-activated

receptor gamma coactivator 1-alphaPI3K Phosphoinositide 3-kinasePKA Protein kinase APPAR Peroxisome proliferator-activated

receptorRCF Rat cardiac fibroblastSirt1 Sirtuin 1SREBP Sterol regulatory element-binding

proteinSTZ StreptozotocinT2DM Type 2 diabetes mellitusTAE Total aqueous extractTAG TriacylglycerolsTBARS Thiobarbituric acid reactive substancesTC Total cholesterolTG TriglyceridesTNF Tumor necrosis factorVLDL Very low-density lipoproteinWAT White adipose tissueWHO World Health Organization

Conflict of Interests

The authors declare that they have no conflict of interests

Acknowledgment

The authors thank Kumar Bishwajit Sutradhar SeniorLecturer Department of Pharmacy Stamford UniversityBangladesh for excellent drawing of the figures in this paper

References

[1] T Kelly W Yang C-S Chen K Reynolds and J He ldquoGlobalburden of obesity in 2005 and projections to 2030rdquo InternationalJournal of Obesity vol 32 no 9 pp 1431ndash1437 2008

[2] M M Finucane G A Stevens M J Cowan et al ldquoNationalregional and global trends in body-mass index since 1980systematic analysis of health examination surveys and epi-demiological studies with 960 country-years and 9sdot1 millionparticipantsrdquoThe Lancet vol 377 no 9765 pp 557ndash567 2011

[3] R Kanter and B Caballero ldquoGlobal gender disparities inobesity a reviewrdquo Advances in Nutrition vol 3 no 4 pp 491ndash498 2012

[4] R W Kimokoti and B E Millen ldquoDiet the global obesityepidemic and preventionrdquo Journal of the American DieteticAssociation vol 111 no 8 pp 1137ndash1140 2011

[5] M L Power and J Schulkin ldquoSex differences in fat storagefat metabolism and the health risks from obesity possibleevolutionary originsrdquo British Journal of Nutrition vol 99 no5 pp 931ndash940 2008


[6] B M Herrera S Keildson and C M Lindgren ldquoGenetics andepigenetics of obesityrdquoMaturitas vol 69 no 1 pp 41ndash49 2011

[7] WHO The World Health Report Reducing Risks PromotingHealthy Life World Health Organization Geneva Switzerland2002

[8] D P Guh W Zhang N Bansback Z Amarsi C L Birming-ham andAHAnis ldquoThe incidence of co-morbidities related toobesity and overweight a systematic review andmeta-analysisrdquoBMC Public Health vol 9 article 88 2009

[9] M M Ibrahim ldquoSubcutaneous and visceral adipose tissuestructural and functional differencesrdquo Obesity Reviews vol 11no 1 pp 11ndash18 2010

[10] J Hoffstedt E Arner HWahrenberg et al ldquoRegional impact ofadipose tissue morphology on the metabolic profile in morbidobesityrdquo Diabetologia vol 53 no 12 pp 2496ndash2503 2010

[11] G SHotamisligil andBM Spiegelman ldquoTumor necrosis factor120572 a key component of the obesity-diabetes linkrdquo Diabetes vol43 no 11 pp 1271ndash1278 1994

[12] S P Weisberg D McCann M Desai M Rosenbaum RL Leibel and A W Ferrante Jr ldquoObesity is associated withmacrophage accumulation in adipose tissuerdquo The Journal ofClinical Investigation vol 112 no 12 pp 1796ndash1808 2003

[13] F I Milagro J Campion and J A Martıez ldquoWeight gaininduced by high-fat feeding involves increased liver oxidativestressrdquo Obesity vol 14 no 7 pp 1118ndash1123 2006

[14] S E Shoelson L Herrero andA Naaz ldquoObesity inflammationand insulin resistancerdquo Gastroenterology vol 132 no 6 pp2169ndash2180 2007

[15] A Abedini and S E Shoelson ldquoInflammation and obesitySTAMPing out insulin resistancerdquo Immunology amp Cell Biologyvol 85 no 6 pp 399ndash400 2007

[16] M C Arkan A L Hevener F R Greten et al ldquoIKK-120573 linksinflammation to obesity-induced insulin resistancerdquo NatureMedicine vol 11 no 2 pp 191ndash198 2005

[17] D Cai M Yuan D F Frantz et al ldquoLocal and systemic insulinresistance resulting from hepatic activation of IKK-120573 and NF-120581Brdquo Nature Medicine vol 11 no 2 pp 183ndash190 2005

[18] N Leuenberger and W Wahli ldquoPPAR120572 A key regulator ofhepatic energy homeostasis in health and diseaserdquo in SignalingPathways in Liver Diseases J F Dufour and P A Clavien Edspp 305ndash315 Springer Berlin Germany 2010

[19] N Venteclef T Jakobsson K R Steffensen and E TreuterldquoMetabolic nuclear receptor signaling and the inflammatoryacute phase responserdquoTrends in Endocrinology andMetabolismvol 22 no 8 pp 333ndash343 2011

[20] S J Bensinger and P Tontonoz ldquoIntegration of metabolism andinflammation by lipid-activated nuclear receptorsrdquo Nature vol454 no 7203 pp 470ndash477 2008

[21] Y-D Wang W-D Chen D D Moore and W Huang ldquoFXRa metabolic regulator and cell protectorrdquo Cell Research vol 18no 11 pp 1087ndash1095 2008

[22] G Chinetti-Gbaguidi J-C Fruchart and B Staels ldquoRole of thePPAR family of nuclear receptors in the regulation of metabolicand cardiovascular homeostasis new approaches to therapyrdquoCurrent Opinion in Pharmacology vol 5 no 2 pp 177ndash1832005

[23] T Wenz ldquoPGC-1120572 activation as a therapeutic approach inmitochondrial diseaserdquo IUBMB Life vol 61 no 11 pp 1051ndash1062 2009

[24] G Lopez-Lluch P M Irusta P Navas and R de CaboldquoMitochondrial biogenesis and healthy agingrdquo ExperimentalGerontology vol 43 no 9 pp 813ndash819 2008

[25] H Pilegaard B Saltin and D P Neufer ldquoExercise inducestransient transcriptional activation of the PGC-1120572 gene inhuman skeletal musclerdquoThe Journal of Physiology vol 546 no3 pp 851ndash858 2003

[26] V A Lira C R Benton Z Yan and A Bonen ldquoPGC-1120572regulation by exercise training and its influences on musclefunction and insulin sensitivityrdquo The American Journal ofPhysiologymdashEndocrinology and Metabolism vol 299 no 2 ppE145ndashE161 2010

[27] J C Corton and H M Brown-Borg ldquoPeroxisome proliferator-activated receptor 120574 coactivator 1 in caloric restriction and othermodels of longevityrdquoThe Journals of Gerontology vol 60 no 12pp 1494ndash1509 2005

[28] J Bastin F Aubey A Rotig A Munnich and F DjouadildquoActivation of peroxisome proliferator-activated receptor path-way stimulates the mitochondrial respiratory chain and cancorrect deficiencies in patientsrsquo cells lacking its componentsrdquoThe Journal of Clinical Endocrinology and Metabolism vol 93no 4 pp 1433ndash1441 2008

[29] M Lagouge C Argmann Z Gerhart-Hines et al ldquoResver-atrol improves mitochondrial function and protects againstmetabolic disease by activating SIRT1 and PGC-1120572rdquo Cell vol127 no 6 pp 1109ndash1122 2006

[30] H Choi H Eo K Park et al ldquoA water-soluble extract fromCucurbita moschata shows anti-obesity effects by controllinglipid metabolism in a high fat diet-induced obesity mousemodelrdquo Biochemical and Biophysical Research Communicationsvol 359 no 3 pp 419ndash425 2007

[31] S H Park S K Ko and S H Chung ldquoEuonymus alatusprevents the hyperglycemia and hyperlipidemia induced byhigh-fat diet in ICR micerdquo Journal of Ethnopharmacology vol102 no 3 pp 326ndash335 2005

[32] N Ikarashi T Toda T Okaniwa K Ito W Ochiai and KSugiyama ldquoAnti-obesity and anti-diabetic effects of Acaciapolyphenol in obese diabetic KKAy mice fed high-fat dietrdquoEvidence-Based Complementary and Alternative Medicine vol2011 Article ID 952031 10 pages 2011

[33] T Nagao Y Komine S Soga et al ldquoIngestion of a tea rich incatechins leads to a reduction in body fat andmalondialdehyde-modified LDL in menrdquo The American Journal of ClinicalNutrition vol 81 no 1 pp 122ndash129 2005

[34] M B Krawinkel and G B Keding ldquoBitter gourd (Momordicacharantia) a dietary approach to hyperglycemiardquo NutritionReviews vol 64 no 7 pp 331ndash337 2006

[35] J K Grover and S P Yadav ldquoPharmacological actions andpotential uses of Momordica charantia a reviewrdquo Journal ofEthnopharmacology vol 93 no 1 pp 123ndash132 2004

[36] M R Khan and A D Omoloso ldquoMomordica charantia andAllium sativum broad spectrum antibacterial activityrdquo KoreanJournal of Pharmacognosy vol 29 no 3 pp 155ndash158 1998

[37] S Lee-Huang P L Huang H-C Chen et al ldquoAnti-HIVand anti-tumor activities of recombinant MAP30 from bittermelonrdquo Gene vol 161 no 2 pp 151ndash156 1995

[38] A Raman and C Lau ldquoAnti-diabetic properties and phyto-chemistry of Momordica charantia L (Cucurbitaceae)rdquo Phy-tomedicine vol 2 no 4 pp 349ndash362 1996

[39] J Kubola and S Siriamornpun ldquoPhenolic contents and antiox-idant activities of bitter gourd (Momordica charantia L) leafstem and fruit fraction extracts in vitrordquo Food Chemistry vol110 no 4 pp 881ndash890 2008

[40] R Horax N Hettiarachchy and S Islam ldquoTotal phenoliccontents and phenolic acid constituents in 4 varieties of bitter


melons (Momordica charantia) and antioxidant activities oftheir extractsrdquo Journal of Food Science vol 70 no 4 pp C275ndashC280 2005

[41] R Horax N Hettiarachchy and P Chen ldquoExtraction quan-tification and antioxidant activities of phenolics from pericarpand seeds of bitter melons (Momordica charantia) harvested atthree maturity stages (Immature Mature and Ripe)rdquo Journal ofAgricultural and Food Chemistry vol 58 no 7 pp 4428ndash44332010

[42] C-I Chang C-R Chen Y-W Liao H-L Cheng Y-CChen and C-H Chou ldquoCucurbitane-type triterpenoids fromMomordica charantiardquo Journal of Natural Products vol 69 no8 pp 1168ndash1171 2006

[43] C-I Chang C-R Chen Y-W Liao H-L Cheng Y-C Chenand C-H Chou ldquoCucurbitane-type triterpenoids from thestems ofMomordica charantiardquo Journal of Natural Products vol71 no 8 pp 1327ndash1330 2008

[44] Y Kimura T Akihisa N Yuasa et al ldquoCucurbitane-typetriterpenoids from the fruit of Momordica charantiardquo Journalof Natural Products vol 68 no 5 pp 807ndash809 2005

[45] J Pitipanapong S Chitprasert M Goto W JiratchariyakulM Sasaki and A Shotipruk ldquoNew approach for extraction ofcharantin from Momordica charantia with pressurized liquidextractionrdquo Separation and Purification Technology vol 52 no3 pp 416ndash422 2007

[46] J-C Chen W-Q Liu L Lu et al ldquoKuguacins F-S cucurbitanetriterpenoids from Momordica charantiardquo Phytochemistry vol70 no 1 pp 133ndash140 2009

[47] S Nakamura T Murakami J Nakamura H Kobayashi HMatsuda and M Yoshikawa ldquoStructures of new cucurbitane-type triterpenes and glycosides karavilagenins and karavilo-sides from the dried fruit of Momordica charantia L in SriLankardquo Chemical amp Pharmaceutical Bulletin vol 54 no 11 pp1545ndash1550 2006

[48] T Akihisa N Higo H Tokuda et al ldquoCucurbitane-typetriterpenoids from the fruits ofMomordica charantia and theircancer chemopreventive effectsrdquo Journal of Natural Productsvol 70 no 8 pp 1233ndash1239 2007

[49] N X Nhiem P V Kiem C V Minh et al ldquoCucurbitane-typetriterpene glycosides from the fruits of Momordica charantiardquoMagnetic Resonance in Chemistry vol 48 no 5 pp 392ndash3962010

[50] Q-Y Li H-B Chen Z-M Liu B Wang and Y-Y ZhaoldquoCucurbitane triterpenoids from Momordica charantiardquo Mag-netic Resonance in Chemistry vol 45 no 6 pp 451ndash456 2007

[51] J Ma P Whittaker A C Keller et al ldquoCucurbitane-typetriterpenoids from Momordica charantiardquo Planta Medica vol76 no 15 pp 1758ndash1761 2010

[52] L Harinantenaina M Tanaka S Takaoka et al ldquoMomordicacharantia constituents and antidiabetic screening of the isolatedmajor compoundsrdquo Chemical and Pharmaceutical Bulletin vol54 no 7 pp 1017ndash1021 2006

[53] Y Liu Z Ali and I A Khan ldquoCucurbitane-type triterpeneglycosides from the fruits of Momordica charantiardquo PlantaMedica vol 74 no 10 pp 1291ndash1294 2008

[54] T Murakami A Emoto H Matsuda and M YoshikawaldquoMedicinal foodstuffs XXI Structures of new cucurbitane-typetriterpene glycosides goyaglycosides-a -b -c -d -e -f -g and-h and new oleanane-type triterpene saponins goyasaponins III and III from the fresh fruit of JapaneseMomordica charantiaLrdquo Chemical and Pharmaceutical Bulletin vol 49 no 1 pp 54ndash63 2001

[55] J-Q Cao B-Y Zhang and Y-Q Zhao ldquoA new cucurbitanetriterpene in acid-treated ethanol extract from Momordicacharantiardquo Chinese Herbal Medicines vol 5 no 3 pp 234ndash2362013

[56] J-Q Liu J-C Chen C-F Wang and M-H Qiu ldquoNew cucur-bitane triterpenoids and steroidal glycoside from MomordicacharantiardquoMolecules vol 14 no 12 pp 4804ndash4813 2009

[57] W-J He L Y Chan R J Clark et al ldquoNovel inhibitor cystineknot peptides fromMomordica charantiardquoPLoSONE vol 8 no10 Article ID e75334 2013

[58] Q Chen and E T S Li ldquoReduced adiposity in bitter melon(Momordica charantia) fed rats is associated with lower tissuetriglyceride and higher plasma catecholaminesrdquo British Journalof Nutrition vol 93 no 5 pp 747ndash754 2005

[59] C-C Shih C-H Lin and W-L Lin ldquoEffects of Momordicacharantia on insulin resistance and visceral obesity in mice onhigh-fat dietrdquoDiabetes Research andClinical Practice vol 81 no2 pp 134ndash143 2008

[60] F Bano N Akthar and H Naz ldquoEffect of the aqueous extractsofMomordica charantia on body weight of ratsrdquo Journal of Basicand Applied Sciences vol 7 pp 1ndash5 2011

[61] P-H ChenG-C ChenM-F Yang et al ldquoBittermelon seed oil-attenuated body fat accumulation in diet-induced obese mice isassociated with cAMP-dependent protein kinase activation andcell death in white adipose tissuerdquoThe Journal of Nutrition vol142 no 7 pp 1197ndash1204 2012

[62] L L Y Chan Q Chen A G G Go E K Y Lam andE T S Li ldquoReduced adiposity in bitter melon (Momordicacharantia)-fed rats is associated with increased lipid oxidativeenzyme activities and uncoupling protein expressionrdquo Journalof Nutrition vol 135 no 11 pp 2517ndash2523 2005

[63] H-L Huang Y-W Hong Y-H Wong et al ldquoBitter melon(Momordica charantia L) inhibits adipocyte hypertrophy anddown regulates lipogenic gene expression in adipose tissue ofdiet-induced obese ratsrdquo British Journal of Nutrition vol 99 no2 pp 230ndash239 2008

[64] D G Popovich L Li andW Zhang ldquoBitter melon (Momordicacharantia) triterpenoid extract reduces preadipocyte viabilitylipid accumulation and adiponectin expression in 3T3-L1 cellsrdquoFood and Chemical Toxicology vol 48 no 6 pp 1619ndash16262010

[65] P V Nerurkar Y-K Lee and V R Nerurkar ldquoMomordicacharantia (bitter melon) inhibits primary human adipocytedifferentiation by modulating adipogenic genesrdquo BMC Comple-mentary and Alternative Medicine vol 10 article 34 2010

[66] A P Jayasooriya M Sakono C Yukizaki M Kawano KYamamoto and N Fukuda ldquoEffects of Momordica charantiapowder on serum glucose levels and various lipid parametersin rats fed with cholesterol-free and cholesterol-enriched dietsrdquoJournal of Ethnopharmacology vol 72 no 1-2 pp 331ndash336 2000

[67] I Ahmed M S Lakhani M Gillett A John and HRaza ldquoHypotriglyceridemic and hypocholesterolemic effectsof anti-diabetic Momordica charantia (karela) fruit extract instreptozotocin-induced diabetic ratsrdquo Diabetes Research andClinical Practice vol 51 no 3 pp 155ndash161 2001

[68] P Chaturvedi S George M Milinganyo and Y B TripathildquoEffect ofMomordica charantia on lipid profile and oral glucosetolerance in diabetic ratsrdquo Phytotherapy Research vol 18 no 11pp 954ndash956 2004

[69] YOishi T SakamotoHUdagawa et al ldquoInhibition of increasesin blood glucose and serum neutral fat byMomordica charantia


saponin fractionrdquo Bioscience Biotechnology and Biochemistryvol 71 no 3 pp 735ndash740 2007

[70] P V Nerurkar Y K Lee M Motosue K Adeli and V RNerurkar ldquoMomordica charantia (bitter melon) reduces plasmaapolipoprotein B-100 and increases hepatic insulin receptorsubstrate and phosphoinositide-3 kinase interactionsrdquo BritishJournal of Nutrition vol 100 no 4 pp 751ndash759 2008

[71] P Chaturvedi and S George ldquoMomordica charantia maintainsnormal glucose levels and lipid profiles and prevents oxidativestress in diabetic rats subjected to chronic sucrose loadrdquo Journalof Medicinal Food vol 13 no 3 pp 520ndash527 2010

[72] R H H Ching L O Y Yeung I M Y Tse W-H Sit andE T S Li ldquoSupplementation of bitter melon to rats fed ahigh-fructose diet during gestation and lactation amelioratesfructose-induced dyslipidemia and hepatic oxidative stress inmale offspringrdquo Journal of Nutrition vol 141 no 9 pp 1664ndash1672 2011

[73] V Gadang W Gilbert N Hettiararchchy R Horax L Katwaand L Devareddy ldquoDietary bitter melon seed increases per-oxisome proliferator-activated receptor-120574 gene expression inadipose tissue down-regulates the nuclear factor-120581B expres-sion and alleviates the symptoms associated with metabolicsyndromerdquo Journal of Medicinal Food vol 14 no 1-2 pp 86ndash93 2011

[74] Y Yu X H Zhang B Ebersole D Ribnicky and Z QWang ldquoBitter melon extract attenuating hepatic steatosis maybe mediated by FGF21 and AMPKSirt1 signaling in micerdquoScientific Reports vol 3 article 3142 2013

[75] S Matsui T Yamane T Takita Y Oishi and K Kobayashi-Hattori ldquoThe hypocholesterolemic activity of Momordica cha-rantia fruit is mediated by the altered cholesterol- and bile acid-regulating gene expression in rat liverrdquo Nutrition Research vol33 no 7 pp 580ndash585 2013

[76] C-C Shih M-T Shlau C-H Lin and J-B Wu ldquoMomordicacharantia ameliorates insulin resistance and dyslipidemia withaltered hepatic glucose production and fatty acid synthesis andAMPK phosphorylation in high-fat-fed micerdquo PhytotherapyResearch vol 28 no 3 pp 363ndash371 2014

[77] N Ahmad M R Hassan H Halder and K S BennoorldquoEffect of Momordica charantia (Karolla) extracts on fastingand postprandial serum glucose levels in NIDDM patientsrdquoBangladesh Medical Research Council Bulletin vol 25 no 1 pp11ndash13 1999

[78] A Tongia S K Tongia and M Dave ldquoPhytochemical deter-mination and extraction of Momordica charantia fruit andits hypoglycemic potentiation of oral hypoglycemic drugs indiabetes mellitus (NIDDM)rdquo Indian Journal of Physiology andPharmacology vol 48 no 2 pp 241ndash244 2004

[79] A M L Dans M V C Villarruz C A Jimeno et al ldquoTheeffect ofMomordica charantia capsule preparation on glycemiccontrol in type 2 diabetes mellitus needs further studiesrdquoJournal of Clinical Epidemiology vol 60 no 6 pp 554ndash5592007

[80] A Fuangchan P Sonthisombat T Seubnukarn et al ldquoHypo-glycemic effect of bitter melon compared with metformin innewly diagnosed type 2 diabetes patientsrdquo Journal of Ethnophar-macology vol 134 no 2 pp 422ndash428 2011

[81] C-H Tsai E C-F Chen H-S Tsay and C-J Huang ldquoWildbitter gourd improves metabolic syndrome a preliminarydietary supplementation trialrdquo Nutrition Journal vol 11 no 1article 4 2012

[82] W Trakoon-osot U Sotanaphun P Phanachet S Pora-suphatana U Udomsubpayakul and S Komindr ldquoPilot studyhypoglycemic and antiglycation activities of bitter melon(Momordica charantia L) in type 2 diabetic patientsrdquo Journalof Pharmacy Research vol 6 no 8 pp 859ndash864 2013

[83] D W Foster ldquoThe role of the carnitine system in humanmetabolismrdquo Annals of the New York Academy of Sciences vol1033 pp 1ndash16 2004

[84] J-Y Kim R C Hickner R L Cortright G L Dohm and J AHoumard ldquoLipid oxidation is reduced in obese human skeletalmusclerdquo The American Journal of PhysiologymdashEndocrinologyand Metabolism vol 279 no 5 pp E1039ndashE1044 2000

[85] R L Dobbins L S Szczepaniak B Bentley V Esser J Myhilland J McGarry ldquoProlonged inhibition of muscle carnitinepalmitoyltransferase-1 promotes intramyocellular lipid accu-mulation and insulin resistance in ratsrdquo Diabetes vol 50 no1 pp 123ndash130 2001

[86] G Perdomo S R Commerford A-M T Richard et alldquoIncreased 120573-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid-induced insulin resistance despite intramyocellular lipid accu-mulationrdquo The Journal of Biological Chemistry vol 279 no 26pp 27177ndash27186 2004

[87] C R Bruce A J Hoy N Turner et al ldquoOverexpression ofcarnitine palmitoyltransferase-1 in skeletal muscle is sufficientto enhance fatty acid oxidation and improve high-fat diet-induced insulin resistancerdquoDiabetes vol 58 no 3 pp 550ndash5582009

[88] P Schrauwen and M Hesselink ldquoUCP2 and UCP3 in musclecontrolling body metabolismrdquo The Journal of ExperimentalBiology vol 205 no 15 pp 2275ndash2285 2002

[89] B A Henry F R DunsheaM Gould and I J Clarke ldquoProfilingpostprandial thermogenesis in muscle and fat of sheep and thecentral effect of leptin administrationrdquo Endocrinology vol 149no 4 pp 2019ndash2026 2008

[90] K-I Wakabayashi M Okamura S Tsutsumi et al ldquoThe per-oxisome proliferator-activated receptor 120574retinoid X receptor120572 heterodimer targets the histone modification enzyme PR-Set7Setd8 gene and regulates adipogenesis through a positivefeedback looprdquo Molecular and Cellular Biology vol 29 no 13pp 3544ndash3555 2009

[91] C Vernochet S B Peres K E Davis et al ldquoCEBP120572 andthe corepressors CtBP1 and CtBP2 regulate repression of selectvisceral white adipose genes during induction of the brownphenotype in white adipocytes by peroxisome proliferator-activated receptor 120574 agonistsrdquo Molecular and Cellular Biologyvol 29 no 17 pp 4714ndash4728 2009

[92] S K Panchal H Poudyal A Iyer et al ldquoHigh-carbohydratehigh-fat diet-induced metabolic syndrome and cardiovascularremodeling in ratsrdquo Journal of Cardiovascular Pharmacologyvol 57 no 5 pp 611ndash624 2011

[93] A D Mooradian ldquoDyslipidemia in type 2 diabetes mellitusrdquoNature Clinical Practice Endocrinology ampMetabolism vol 5 no3 pp 150ndash159 2009

[94] T J Chahil and H N Ginsberg ldquoDiabetic dyslipidemiardquoEndocrinology andMetabolism Clinics of North America vol 35no 3 pp 491ndash510 2006

[95] T ChongMNaples L Federico et al ldquoEffect of rosuvastatin onhepatic production of apolipoprotein B-containing lipoproteinsin an animal model of insulin resistance and metabolic dyslipi-demiardquo Atherosclerosis vol 185 no 1 pp 21ndash31 2006


[96] C Taghibiglou F Rashid-Kolvear S C Van Iderstine et alldquoHepatic very low density lipoprotein-ApoB overproduction isassociated with attenuated hepatic insulin signaling and over-expression of protein-tyrosine phosphatase 1B in a fructose-fedhamster model of insulin resistancerdquo The Journal of BiologicalChemistry vol 277 no 1 pp 793ndash803 2002

[97] R Streicher J Kotzka D Muller-Wieland et al ldquoSREBP-1mediates activation of the low density lipoprotein receptorpromoter by insulin and insulin-like growth factor-Irdquo TheJournal of Biological Chemistry vol 271 no 12 pp 7128ndash71331996

[98] P Puigserver and B M Spiegelman ldquoPeroxisome proliferator-activated receptor-120574 coactivator 1120572 (PGC-1120572) transcriptionalcoactivator andmetabolic regulatorrdquoEndocrine Reviews vol 24no 1 pp 78ndash90 2003

[99] R B Vega J M Huss and D P Kelly ldquoThe coactivator PGC-1 cooperates with peroxisome proliferator-activated receptoralpha in transcriptional control of nuclear genes encodingmitochondrial fatty acid oxidation enzymesrdquo Molecular andCellular Biology vol 20 no 5 pp 1868ndash1876 2000

[100] M B Hock andA Kralli ldquoTranscriptional control ofmitochon-drial biogenesis and functionrdquoAnnual Review of Physiology vol71 pp 177ndash203 2009

[101] B B Zhang G Zhou and C Li ldquoAMPK an emerging drug tar-get for diabetes and the metabolic syndromerdquo Cell Metabolismvol 9 no 5 pp 407ndash416 2009

[102] C Canto and J Auwerx ldquoPGC-1120572 SIRT1 and AMPK an energysensing network that controls energy expenditurerdquo CurrentOpinion in Lipidology vol 20 no 2 pp 98ndash105 2009

[103] B N Finck and D P Kelly ldquoPGC-1 coactivators inducibleregulators of energy metabolism in health and diseaserdquo TheJournal of Clinical Investigation vol 116 no 3 pp 615ndash6222006

[104] D G Hardie ldquoAMPK a key regulator of energy balance in thesingle cell and the whole organismrdquo International Journal ofObesity vol 32 no S4 pp S7ndashS12 2008

[105] H Zong J M Ren L H Young et al ldquoAMP kinase is requiredfor mitochondrial biogenesis in skeletal muscle in responseto chronic energy deprivationrdquo Proceedings of the NationalAcademy of Sciences of the United States of America vol 99 no25 pp 15983ndash15987 2002

[106] P M Garcia-Roves M E Osler M H Holmstrom and J RZierath ldquoGain-of-function R225Q mutation in AMP-activatedprotein kinase 1205743 subunit increasesmitochondrial biogenesis inglycolytic skeletal musclerdquo The Journal of Biological Chemistryvol 283 no 51 pp 35724ndash35734 2008

[107] Y C Long B R Barnes M Mahlapuu et al ldquoRole of AMP-activated protein kinase in the coordinated expression of genescontrolling glucose and lipid metabolism in mouse whiteskeletal musclerdquo Diabetologia vol 48 no 11 pp 2354ndash23642005

[108] D J Peet S D Turley W Ma et al ldquoCholesterol and bile acidmetabolism are impaired in mice lacking the nuclear oxysterolreceptor LXR120572rdquo Cell vol 93 no 5 pp 693ndash704 1998

[109] B P Chaudhari V J Chaware Y R Joshi and K RBiyani ldquoHepatoprotective activity of hydroalcoholic extract ofMomordica charantia Linn leaves against carbon tetra chlorideinduced hepatopathy in ratsrdquo International Journal of ChemTechResearch vol 1 no 2 pp 355ndash358 2009

[110] A J Thenmozhi and P Subramanian ldquoAntioxidant poten-tial of Momordica charantia in ammonium chloride-induced

hyperammonemic ratsrdquo Evidence-Based Complementary andAlternative Medicine vol 2011 Article ID 612023 7 pages 2011

[111] K Zahra M A Malik M S Mughal M Arshad and MI Sohail ldquoHepatoprotective role of extracts of Momordicacharantia L in acetaminophen-induced toxicity in rabbitsrdquoJournal of Animal and Plant Sciences vol 22 no 2 pp 273ndash2772012

[112] R H H Ching L O Y Yeung I M Y Tse W-H Sit andE T S Li ldquoSupplementation of bitter melon to rats fed ahigh-fructose diet during gestation and lactation amelioratesfructose-induced dyslipidemia and hepatic oxidative stress inmale offspringrdquo The Journal of Nutrition vol 141 no 9 pp1664ndash1672 2011


[114] S K Mantena A L King K K Andringa H B Eccleston andS M Bailey ldquoMitochondrial dysfunction and oxidative stressin the pathogenesis of alcohol- and obesity-induced fatty liverdiseasesrdquo Free Radical Biology amp Medicine vol 44 no 7 pp1259ndash1272 2008

[115] L Tappy and K-A Le ldquoMetabolic effects of fructose and theworldwide increase in obesityrdquo Physiological Reviews vol 90no 1 pp 23ndash46 2010

[116] K L Stanhope and P J Havel ldquoFructose consumption recentresults and their potential implicationsrdquoAnnals of the New YorkAcademy of Sciences vol 1190 no 1 pp 15ndash24 2010

[117] M M Abdullah N N Riediger Q Chen et al ldquoEffects oflong-term consumption of a high-fructose diet on conventionalcardiovascular risk factors in sprague-dawley ratsrdquo Molecularand Cellular Biochemistry vol 327 no 1-2 pp 247ndash256 2009

[118] G Morris-Stiff and A E Feldstein ldquoFibroblast growth factor21 as a biomarker for NAFLD integrating pathobiology intoclinical practicerdquo Journal of Hepatology vol 53 no 5 pp 795ndash796 2010

[119] H Li Q Fang F Gao et al ldquoFibroblast growth factor 21 levelsare increased in nonalcoholic fatty liver disease patients and arecorrelated with hepatic triglyceriderdquo Journal of Hepatology vol53 no 5 pp 934ndash940 2010

[120] C Day T Cartwright J Provost and C J Bailey ldquoHypogly-caemic effect ofMomordica charantia extractsrdquo Planta Medicavol 56 no 5 pp 426ndash429 1990

[121] L Ali A K Azad Khan M I Rouf Mamun et al ldquoStudieson hypoglycemic effects of fruit pulp seed and whole plantof Momordica charantia on normal and diabetic model ratsrdquoPlanta Medica vol 59 no 5 pp 408ndash412 1993

[122] Y Srivastava H Venkatakrishna-Bhatt Y Verma K Venkaiahand B H Raval ldquoAntidiabetic and adaptogenic propertiesof Momordica charantia extract an experimental and clinicalevaluationrdquo Phytotherapy Research vol 7 no 4 pp 285ndash2891993

[123] S Sarkar M Pranava and R A Marita ldquoDemonstration ofthe hypoglycemic action ofMomordica charantia in a validatedanimal model of diabetesrdquo Pharmacological Research vol 33no 1 pp 1ndash4 1996

[124] J Virdi S Sivakami S Shahani A C SutharMM Banavalikarand M K Biyani ldquoAntihyperglycemic effects of three extractsfromMomordica charantiardquo Journal of Ethnopharmacology vol88 no 1 pp 107ndash111 2003

[125] J A O Ojewole S O Adewole and G Olayiwola ldquoHypo-glycaemic and hypotensive effects of Momordica charantia


Linn (Cucurbitaceae) whole-plant aqueous extract in ratsrdquoCardiovascular Journal of South Africa vol 17 no 5 pp 227ndash232 2006

[126] M G Sridhar R Vinayagamoorthi V A SuyambunathanZ Bobby and N Selvaraj ldquoBitter gourd (Momordica charan-tia) improves insulin sensitivity by increasing skeletal muscleinsulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed ratsrdquo British Journal of Nutrition vol 99 no 4 pp 806ndash8122008

[127] P Chaturvedi ldquoAntidiabetic potentials ofmomordica charantiamultiple mechanisms behind the effectsrdquo Journal of MedicinalFood vol 15 no 2 pp 101ndash107 2012

[128] I Ahmed E Adeghate E Cummings A K Sharma andJ Singh ldquoBeneficial effects and mechanism of action ofMomordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in ratrdquo Molecular and Cellular Bio-chemistry vol 261 no 1 pp 63ndash70 2004

[129] M F Mahomoodally A-G Fakim and A H SubrattyldquoMomordica charantia extracts inhibit uptake of monosac-charide and amino acid across rat everted gut sacs in-vitrordquoBiological and Pharmaceutical Bulletin vol 27 no 2 pp 216ndash218 2004

[130] Z Ahmad K F Zamhuri A Yaacob et al ldquoIn vitro anti-diabeticactivities and chemical analysis of polypeptide-k and oil isolatedfrom seeds of Momordica charantia (bitter gourd)rdquo Moleculesvol 17 no 8 pp 9631ndash9640 2012

[131] N G Sahib A A Hamid N Saari F Abas M S P Dek andM Rahim ldquoAnti-pancreatic lipase and antioxidant activity ofselected tropical herbsrdquo International Journal of Food Propertiesvol 15 no 3 pp 569ndash578 2012

[132] YOishi T SakamotoHUdagawa et al ldquoInhibition of increasesin blood glucose and serum neutral fat byMomordica charantiasaponin fractionrdquo Bioscience Biotechnology and Biochemistryvol 71 no 3 pp 735ndash740 2007

[133] T Miura C Itoh N Iwamoto et al ldquoHypoglycemic activity ofthe fruit of the Momordica charantia in type 2 diabetic micerdquoJournal of Nutritional Science and Vitaminology vol 47 no 5pp 340ndash344 2001

[134] C-C Shih C-H Lin W-L Lin and J-B Wu ldquoMomordicacharantia extract on insulin resistance and the skeletal muscleGLUT4 protein in fructose-fed ratsrdquo Journal of Ethnopharma-cology vol 123 no 1 pp 82ndash90 2009

[135] E Cummings H S Hundal H Wackerhage et al ldquoMomordicacharantia fruit juice stimulates glucose and amino acid uptakesin L6 myotubesrdquoMolecular and Cellular Biochemistry vol 261no 1 pp 99ndash104 2004

[136] R Kumar S Balaji T S Uma and P K Sehgal ldquoFruit extracts ofMomordica charantia potentiate glucose uptake and up-regulateGlut-4 PPAR120574 and PI3Krdquo Journal of Ethnopharmacology vol126 no 3 pp 533ndash537 2009

[137] B W C Roffey A S Atwal T Johns and S Kubow ldquoWaterextracts from Momordica charantia increase glucose uptakeand adiponectin secretion in 3T3-L1 adipose cellsrdquo Journal ofEthnopharmacology vol 112 no 1 pp 77ndash84 2007

[138] I Ahmed E Adeghate A K Sharma D J Pallot and J SinghldquoEffects ofMomordica charantia fruit juice on islet morphologyin the pancreas of the streptozotocin-diabetic ratrdquo DiabetesResearch and Clinical Practice vol 40 no 3 pp 145ndash151 1998

[139] D Sathishsekar and S Subramanian ldquoBeneficial effects ofMomordica charantia seeds in the treatment of STZ-induceddiabetes in experimental ratsrdquo Biological and PharmaceuticalBulletin vol 28 no 6 pp 978ndash983 2005

[140] R M Hafizur N Kabir and S Chishti ldquoModulation of pancre-atic 120573-cells in neonatally streptozotocin-induced type 2 diabeticrats by the ethanolic extract ofMomordica charantia fruit pulprdquoNatural Product Research vol 25 no 4 pp 353ndash367 2011

[141] N Singh and M Gupta ldquoRegeneration of 120573 cells in islets ofLangerhans of pancreas of alloxan diabetic rats by acetoneextract of Momordica charantia (Linn) (bitter gourd) fruitsrdquoIndian Journal of Experimental Biology vol 45 no 12 pp 1055ndash1062 2007

[142] S Yibchok-Anun S Adisakwattana C Y Yao P Sangvanich SRoengsumran andWHHsu ldquoSlow acting protein extract fromfruit pulp of Momordica charantia with insulin secretagogueand insulinomimetic activitiesrdquo Biological and PharmaceuticalBulletin vol 29 no 6 pp 1126ndash1131 2006

[143] A C Keller J Ma A Kavalier K He A-M B Brillantesand E J Kennelly ldquoSaponins from the traditional medicinalplantMomordica charantia stimulate insulin secretion in vitrordquoPhytomedicine vol 19 no 1 pp 32ndash37 2011

[144] Q Chen L L Y Chan and E T S Li ldquoBittermelon (Momordicacharantia) reduces adiposity lowers serum insulin and normal-izes glucose tolerance in rats fed a high fat dietrdquoThe Journal ofNutrition vol 133 no 4 pp 1088ndash1093 2003

[145] H-Y Lo T-Y Ho C Lin C-C Li and C-Y HsiangldquoMomordica charantia and its novel polypeptide regulate glu-cose homeostasis in mice via binding to insulin receptorrdquoJournal of Agricultural and Food Chemistry vol 61 no 10 pp2461ndash2468 2013

[146] D L Clouatre S N Rao and H G Preuss ldquoBitter melonextracts in diabetic and normal rats favorably influence bloodglucose and blood pressure regulationrdquo Journal of MedicinalFood vol 14 no 12 pp 1496ndash1504 2011

[147] C-H Tsai E C-F Chen H-S Tsay and C-J Huang ldquoWildbitter gourd improves metabolic syndrome a preliminarydietary supplementation trialrdquo Nutrition Journal vol 11 article4 2012

[148] S-J Wu and L-T Ng ldquoAntioxidant and free radical scavengingactivities of wild bitter melon (Momordica charantia Linn varabbreviata Ser) in Taiwanrdquo LWT Food Science and Technologyvol 41 no 2 pp 323ndash330 2008

[149] R Horax N Hettiarachchy and P Chen ldquoExtraction quan-tification and antioxidant activities of phenolics from pericarpand seeds of bitter melons (Momordica charantia) harvested atthree maturity stages (immature mature and ripe)rdquo Journal ofAgricultural and Food Chemistry vol 58 no 7 pp 4428ndash44332010

[150] R Kumar S Balaji R Sripriya N Nithya T S Uma and PK Sehgal ldquoIn vitro evaluation of antioxidants of fruit extractof Momordica charantia L on fibroblasts and keratinocytesrdquoJournal of Agricultural and Food Chemistry vol 58 no 3 pp1518ndash1522 2010

[151] L Leung R Birtwhistle J Kotecha SHannah and S Cuthbert-son ldquoAnti-diabetic and hypoglycaemic effects of Momordicacharantia (bitter melon) a mini reviewrdquo British Journal ofNutrition vol 102 no 12 pp 1703ndash1708 2009

[152] C P Ooi Z Yassin and T A Hamid ldquoMomordica charantiafor type 2 diabetes mellitusrdquo Cochrane Database of SystematicReviews no 8 Article ID CD007845 2012

2 Journal of Lipids

and glucose regulating hormones adipokines and cytokineslike adiponectin leptin and tumor necrosis factor-120572 (TNF-120572) [9 10] Increased concentration and expression of TNF-120572interleukin-6 (IL-6) andmonocyte chemoattractant protein-1 (MCP-1) are evident in adipocyte dysfunction and insulinresistance [11] Furthermore inflammatory cells such asmacrophages infiltration are also increased in adipose tissues[12] Proinflammatory cytokines and oxidative stress havealso been shown to be responsible for developing metabolicdisturbances such as insulin resistance and activation ofimmune response in liver adipose tissue and muscle [13ndash15] Moreover activation of inflammatory pathways in hep-atocytes is sufficient to cause both local as well as systemicinsulin resistance [16 17]

In the last decade much attention has been focusedon several molecular drug targets with the potential toprevent or treat metabolic disorders Thus nuclear receptorsand their regulators have attracted much attention dueto their regulatory role in both glucose homeostasis andlipogenesis [18] Peroxisome proliferator-activated receptors(PPARs) and liver X receptors (LXRs) are two regulatoryproteins identified to play a pivotal role in the regulationof metabolic homeostasis [19ndash21] while PPARs activationis important for lipid metabolism adipocyte differentiationand the prevention of inflammation [22] PPARs also regu-late mitochondrial biogenesis via an activator called PGC-1120572 [23 24] which is physiologically regulated by exercise[25 26] and calorie restriction [27] In addition to thesefactors pharmacological agents such as fenofibrates [28]and resveratrol [29] may also stimulate PGC-1120572 and restoremitochondrial function Recent reports suggest that naturalproducts are rich source of ligands for nuclear receptorsand are promising therapeutic agents in clinical practiceResearchers have also examined the effects of various func-tional foods on overall body composition and selective fatdepots Water-soluble extract of Cucurbita moschata stem(500mgkgday for 8 weeks) activated PPAR-120572 increased120573-oxidation and inhibited adipocyte differentiation in adose dependent manner [30] Extracts of Euonymus alatusincreased the expression of PPAR-120574 in periepididymal fatpad and ameliorated the hyperglycemia and hyperlipidemiainduced by high-fat diet in vivo [31] Acacia polyphenolsincreased the mRNA expression of fat metabolizing geneslike PPAR-120572 and PPAR-120575 in skeletal muscle and loweredthe expression of fat acid synthesis-related genes (SREBP-1cACC and FAS) in the liver [32] Green tea catechins have alsobeen proposed as therapeutic agents for body fat reduction[33]

Bitter melon (Momordica charantia L) is widely used forthe treatment of diabetes Recent research reports suggest thatbitter melon extracts may ameliorate high fat diet inducedobesity and hyperlipidemia in animal model Most findingsrelated to obesity and hyperlipidemia also showed that theplant extracts may modulate fat metabolizing kinases suchas AMPKs genes and nuclear factors like PPARs LXRs andPGC-1120572 in liver and skeletal muscle and affected adipocytedifferentiationwhile several reviewpapers suggest the antidi-abetic mechanism [34] and various pharmaceutical effects ofthe plant [35] and emphasized its efficacy and safety aspects

Figure 1 Fruits of different variety ofMomordica charantia availablein Bangladesh Upper left one is commonly known as Korolla andright one as Ucche

Therefore the present review aims to describe the effect ofbitter melon extracts on various parameters of metabolicsyndrome obesity and related cardiovascular complicationsMoreover this review will also find out the plausible mech-anisms responsible for antiobesity and hypolipidemic effectsof the plant based on available information to date

2 Bitter Melon Overview and TraditionalMedicinal Uses

Bitter melon is a climbing shrub cultivated mainly inBangladesh India China and Korea mostly in Asian coun-tries The plant also grows in tropical areas of Amazon EastAfrica and the Caribbean It belongs to family Cucurbitaceaeand the scientific name is Momordica charantia Generallytwo varieties of the plant are found in Bangladesh while thesmall size one is locally called ldquoUccherdquo and the large sizeone is locally known as ldquoKorollardquo (Figure 1) However someother wild type African species are also found in the countrythat include M balsamina L M foetida Schum and Mrostrata A Zimm Bitter melon fruits are taken as culinaryvegetable in Bangladesh and in Indian subcontinent it is alsoused as a traditional medicinal plant for the treatment ofvarious diseases in Bangladesh as well as other developingcountries like Brazil China Colombia Cuba Ghana HaitiIndia Mexico Malaya Nicaragua Panama and Peru [35]Perhaps the most common traditional use of the plant isto treat diabetes in different countries around the globe Itis also used for the treatment of various other pathologicalconditions such as dysmenorrhea eczema emmenagoguegalactagogue gout jaundice kidney (stone) leprosy leucor-rhea piles pneumonia psoriasis rheumatism and scabies[35] Momordica charantia are also documented to possessabortifacient anthelmintic contraceptive antimalarial andlaxative properties [35]

Recent scientific exploration on this plant elucidatedpotential biological effect on both animal and clinical studiesApart from its potential antibacterial [36] and antiviral activi-ties [37] bittermelon extracts are also effective against cancerand were found to be effective for the treatment of ulcermalaria pain and inflammation psoriasis dyslipidemia andhypertensionMomordica charantia also contains biologicallyactive chemical compounds such as glycosides saponins

Journal of Lipids 3










OHOH

H H

COOH

OMe

OH

H H

COOH

OHOH

COOH

HO

HO

O

OH O

OH

OH

OH

OH

HO











4 Journal of Lipids

Kuguacin AHO

OHOHC

OHO

OH

O


HO O

O

HO

OHC

O

O

Kuguacin D

HO O

O

O


OHC

O

O

O

O

OHC

O

O

O

O

OH

Kuguacin G

O-glucoseCharantin

CH(CH3)2

H3C

OHC

O

O

O

OH

Kuguacin HO

O

OO

OMe

Kuguacin I

OHC

OHHO

Kuguacin J

COOH

OHC

OOO

Kuguacin K

OO

OO

Kuguacin M

OHC

OHHO

O

Kuguacin N

OHC

OO

O

Kuguacin O

Kuguacin P

O

O

OO

HH

O

O

OO

OEtH

Kuguacin Q

HOO

HHO

OH

Kuguacin R

OHC

O

OH

O

Kuguacin S

OHC

HO OH

OH

Momordicine I

HO

OMe

OMe

Karavilagenin A

HO

OH

OMe

Karavilagenin B

HO OMe

Karavilagenin C

Kuguacin L

OO

O

CH2OH

H




Journal of Lipids 5

RO

O

HH

RO

O

HH OMe

OMe

OMe

OH

O

MeOCOOH

OHOH


OH

OH

OH

OH

H

OR

Momordicoside A


Xyl-pyr


R = -Glu-pyr

OHOH

OH

H

Momordicoside C


CHOH

Momordicoside E


OHH

OH

Momordicoside D


O

HH

OMe


O

HHOMe OMe


HO

OROHC



O


OR1

R2O

R2O

OR1

OR1

OR1

R2O R2O







6 Journal of Lipids



075 and 15extracts



075 and 15extracts


[62]



extracts


[59]



[63]



[60]


15 and 30 of diet


[61]




[65]






Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































Journal of Lipids 3










OHOH

H H

COOH

OMe

OH

H H

COOH

OHOH

COOH

HO

HO

O

OH O

OH

OH

OH

OH

HO











4 Journal of Lipids

Kuguacin AHO

OHOHC

OHO

OH

O


HO O

O

HO

OHC

O

O

Kuguacin D

HO O

O

O


OHC

O

O

O

O

OHC

O

O

O

O

OH

Kuguacin G

O-glucoseCharantin

CH(CH3)2

H3C

OHC

O

O

O

OH

Kuguacin HO

O

OO

OMe

Kuguacin I

OHC

OHHO

Kuguacin J

COOH

OHC

OOO

Kuguacin K

OO

OO

Kuguacin M

OHC

OHHO

O

Kuguacin N

OHC

OO

O

Kuguacin O

Kuguacin P

O

O

OO

HH

O

O

OO

OEtH

Kuguacin Q

HOO

HHO

OH

Kuguacin R

OHC

O

OH

O

Kuguacin S

OHC

HO OH

OH

Momordicine I

HO

OMe

OMe

Karavilagenin A

HO

OH

OMe

Karavilagenin B

HO OMe

Karavilagenin C

Kuguacin L

OO

O

CH2OH

H




Journal of Lipids 5

RO

O

HH

RO

O

HH OMe

OMe

OMe

OH

O

MeOCOOH

OHOH


OH

OH

OH

OH

H

OR

Momordicoside A


Xyl-pyr


R = -Glu-pyr

OHOH

OH

H

Momordicoside C


CHOH

Momordicoside E


OHH

OH

Momordicoside D


O

HH

OMe


O

HHOMe OMe


HO

OROHC



O


OR1

R2O

R2O

OR1

OR1

OR1

R2O R2O







6 Journal of Lipids



075 and 15extracts



075 and 15extracts


[62]



extracts


[59]



[63]



[60]


15 and 30 of diet


[61]




[65]






Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































4 Journal of Lipids

Kuguacin AHO

OHOHC

OHO

OH

O


HO O

O

HO

OHC

O

O

Kuguacin D

HO O

O

O


OHC

O

O

O

O

OHC

O

O

O

O

OH

Kuguacin G

O-glucoseCharantin

CH(CH3)2

H3C

OHC

O

O

O

OH

Kuguacin HO

O

OO

OMe

Kuguacin I

OHC

OHHO

Kuguacin J

COOH

OHC

OOO

Kuguacin K

OO

OO

Kuguacin M

OHC

OHHO

O

Kuguacin N

OHC

OO

O

Kuguacin O

Kuguacin P

O

O

OO

HH

O

O

OO

OEtH

Kuguacin Q

HOO

HHO

OH

Kuguacin R

OHC

O

OH

O

Kuguacin S

OHC

HO OH

OH

Momordicine I

HO

OMe

OMe

Karavilagenin A

HO

OH

OMe

Karavilagenin B

HO OMe

Karavilagenin C

Kuguacin L

OO

O

CH2OH

H




Journal of Lipids 5

RO

O

HH

RO

O

HH OMe

OMe

OMe

OH

O

MeOCOOH

OHOH


OH

OH

OH

OH

H

OR

Momordicoside A


Xyl-pyr


R = -Glu-pyr

OHOH

OH

H

Momordicoside C


CHOH

Momordicoside E


OHH

OH

Momordicoside D


O

HH

OMe


O

HHOMe OMe


HO

OROHC



O


OR1

R2O

R2O

OR1

OR1

OR1

R2O R2O







6 Journal of Lipids



075 and 15extracts



075 and 15extracts


[62]



extracts


[59]



[63]



[60]


15 and 30 of diet


[61]




[65]






Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































Journal of Lipids 5

RO

O

HH

RO

O

HH OMe

OMe

OMe

OH

O

MeOCOOH

OHOH


OH

OH

OH

OH

H

OR

Momordicoside A


Xyl-pyr


R = -Glu-pyr

OHOH

OH

H

Momordicoside C


CHOH

Momordicoside E


OHH

OH

Momordicoside D


O

HH

OMe


O

HHOMe OMe


HO

OROHC



O


OR1

R2O

R2O

OR1

OR1

OR1

R2O R2O







6 Journal of Lipids



075 and 15extracts



075 and 15extracts


[62]



extracts


[59]



[63]



[60]


15 and 30 of diet


[61]




[65]






Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































6 Journal of Lipids



075 and 15extracts



075 and 15extracts


[62]



extracts


[59]



[63]



[60]


15 and 30 of diet


[61]




[65]






Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































Journal of Lipids 7

Liver



Pancreas



Fat cells









8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































8 Journal of Lipids






weeks





[58]







[70]




[71]


1 of diet


[72]



[73]



[74]



[75]




[76]




Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References


































































































































































Journal of Lipids 9
























[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References



















































































































































































[77]




[78]





[79]





[80]





[81]





[82]






2O2and xan-



AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References



































































































































































AMPK AMPK

AMPK

PPAR-120574PPAR-120574

PPAR-120574

SREBP-1c

Transcription

FAS


Palmitate

LDLoxidation

Adiponectin

LeptinOxLDL

Nucleus


LXRsCell membrane

p

d

p

PGC1120572










Abbreviations
















Acknowledgment


References




































































































































































Abbreviations
















Acknowledgment


References


































































































































































Beneficial Role of Bitter Melon Supplementation in Obesity ... · ReviewArticle Beneficial Role of...

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Transcript of Beneficial Role of Bitter Melon Supplementation in Obesity ... · ReviewArticle Beneficial Role of...