Review of Medicinal Plants for Anti-Obesity Activity...Review of Medicinal Plants for Anti-Obesity...

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Translational BiomedicineISSN 2172-0479

2015Vol. 6 No. 3:21

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Review Article

DOI: 10.21767/2172-0479.100021

Satyajit Patra1, S Nithya2, B Srinithya2 and Meenakshi SM2

1 DivisionofBiochemistryandGenetics,AmericanInternationalMedicalUniversity,SaintLucia,WI,USA

2 DepartmentofBiotechnology,SchoolofChemical&Biotechnology,SASTRAUniversity,Thirumalaisamudram,Thanjavur,Tamilnadu,India–613401

Corresponding author: Dr.SatyajitPatra

[email protected]

DivisionofBiochemistryandGenetics,AmericanInternationalMedicalUniversity,SaintLucia,WI,USA.

Tel: 1-758-488-0322

Citation:PatraS,NithyaS,SrinithyaB,etal. ReviewofMedicinalPlantsforAnti-ObesityActivity.TranslBiomed.2015,6:3.

IntroductionInthepresentscenario,obesityisthemajorpublichealthproblemwithabout1.9billionadults(18yearsandolder)worldwideareoverweight and about 600million of themare clinically obese[1].Obesityischaracterizedbyincreaseinadiposecellsizewhichisdeterminedbyamountoffataccumulatedinthecytoplasmofadipocytes[2].Thischangeinthemetabolismintheadipocytesis regulated by various enzymes such as fatty acid synthase,lipoproteinlipaseandadipocytefattyacid-bindingprotein[3].

Obesity results from an imbalance between energy intake andexpenditure. It is caused by altered lipid metabolic processesincludinglipogenesisandlipolysis[4].Lipogenesisistheprocessthat stores free fatty acids in the form of triglyceride (TG)[5]; similarly, lipolysis is the process whereby the TG storedis metabolized to free fatty acids and glycerol [6]. Obesityaccompaniedbyhyperlipidemiawhichisindicatedbyabnormallyhighconcentrationof lipids inblood[7].Theadiposetissue,anendocrineorgan,hasamajorroleintheregulationofmetabolismand homeostasis, through the secretion of several biologicallyactiveadipokines[8].Duringadiposetissuedevelopment,three

major transcription factors, peroxisome proliferator-activatedreceptor(PPAR)γ,CCAAT/enhancerbindingprotein(C/EBP)α,andsterol regulatory element-binding protein (SREBP) 1c, regulatetheexpressionoftheselipid-metabolizingenzymes[9].5'AMP-activatedproteinkinase(AMPK)playsamajorroleinglucoseandlipidmetabolismbyinactivatingacetyl-CoAcarboxylase(ACC)andstimulatesfattyacidoxidationbyup-regulatingtheexpressionofcarnitinepalmitoyltransferase-1(CPT-1),PPARα,anduncouplingprotein[10].

Nowadays,changesinhumanlifestyleandhighenergydiethaveincreasedtheincidenceofobesityandevenhavebecomeariskfactor to the population of children [11,12]. There are severalpharmacologicsubstancesavailableasantiobesitydrugs,howeverthey have hazardous side effects and hence natural productshavebeenusedfortreatingobesityinmanyAsiancountries[13].Thepotentialofnaturalproductsforthetreatmentofobesityisstilllargelyunexploredandcanbeanexcellentalternativeforthesafeandeffectivedevelopmentofantiobesitydrugs[14].

Currentlydrugsavailableinthemarketfortreatmentofobesitycanbedividedintotwomajorclassesonebeingorlistat,which

Review of Medicinal Plants for Anti-Obesity Activity

AbstractObesityisacomplexhealthissuetoaddress,itisaseriousandchronicdiseasethatcanhaveanegativeeffectonmanysystemsinyourbody.Overweightandobesitymayincreasetheriskofmanyhealthproblems,includingdiabetes,heartdisease,osteoarthritis and certain cancers. Obesity is increasing at an alarming ratethroughouttheworld.Todayitisestimatedthattherearemorethan300millionobesepeopleworld-wide.Obesity isregardedasadisorderof lipidmetabolismand the enzymes involved in this process could be targeted selectively for thedevelopmentofantiobesitydrugs.However,mostoftheanti-obesitydrugsthatwereapprovedandmarketedhavenowbeenwithdrawnduetoseriousadverseeffects. The naturopathic treatment for obesity has been explored extensivelysinceancienttimesandgainingmomentuminthepresentscenario.Traditionalmedicinal plants and their active phytoconstituents have been used for thetreatmentofobesityandtheirassociatedsecondarycomplications.Someactivemedicinalplantsand their respectivebioactivecompoundswerealso testedbyclinicaltrialsandareeffectiveintraemnetofobesity.Thisreviewfocusonnaturalphytoextractswiththeirmechanismofactionandtheirpreclinicalexperimentalmodelforfurtherscientificresearch.

Keywords: Obesity;Antiobesitydrugs;Medicinalplants

Received: August20,2015; Accepted: December01,2015; Published: December04,2015

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reduces fat absorption through inhibition of pancreatic lipaseandthesecondissubutraminewhichisananorecticorappetitesuppressant.Bothdrugshaveadverseeffectsincludingincreasedbloodpressure,headache,drymouth,insomnia,andconstipation[15,16]. In 1990 Fenfluramine and Dexfenfluramine werewithdrawnfromthemarketbecauseofheartvalvedamage[17].TheUSFDAin1997approvedsubutraminedrugasatreatmentforobesity.But later inOctober2010 thedrugwaswithdrawnfrom the market due to increased cardiovascular events andstrokes[18,19]. InFebruary2011theUSFDArejectedapprovalofcontrivewhichisacombinationofbupropion/naltrexoneduetoconcernsoverpotentialcardiovascularrisks[20].Certaindrugshavepotentialforabusesuchasphentermineanddiethylpropionandhenceareapprovedforshorttermuse[21].

Atpresent,becauseofhighcostandpotentiallyhazardoussideeffects, the need for natural products against obesity is underexplorationwhichmaybeanalternativestrategyfordevelopingeffective, safeantiobesitydrugs [22]. In2000,MoroandBasilereportedtheuseofcertainwellknownmedicinalplantsthathadclaimedtobeuseful intreatingobesity.Theantiobesityeffectsofnaturalproductsfrommorediversesources[23].Theaimofthepresentreviewwastoupdatedataonpotentialantiobesityherbalplants.

MethodsDatabases used for this study to search include PubMed,Scopus, Google Scholar, Web of Science, and IranMedex withinformationreportedbetweenSeptember2,2006toSeptember22,2014.Searchofliteratureswasfocusedonhumanoranimalsinvestigatingthebenefitsandharmsofherbalmedicinestotreatobesity.Thesearchtermswere“obesity”and(“herbalmedicine”or“plant”,“plantmedicinal”or“medicinetraditional”)withoutnarrowingorlimitingsearchitems.Publicationswithabstractfromthementioneddatabaseswereusedtopreparethisreview.Themainoutcomemeasuresweredefinedasbodyweight,bodyfat,includingfatmass/fatweightorfatpercentage/visceraladiposetissueweight,waistorhipcircumference,tricepsthicknessandappetite, and the amount of food/energy intake. Abstracts of

publicationsonplantsused toevaluate theactivityonhuman,animals,celllinesstudieswiththemainoutcomeasmentionedabovewereincluded.Invitrostudies,reviewarticlesandletterstotheeditorwereexcluded.Tworeviewersreviewedthearticlesforabstractsandtitle.Duetoourinclusionandexclusioncriteria,the duplicate articles were eliminated. The review includesactivecomponentsandmechanismofactionagainstobesity inanimalsandpresentedinTable 1.SomeoftheplantsaretestedfortheiractivityagainstobesityincelllineslistedinTable 2 and plantsthatweretestedonhumanvolunteersorclinicaltrailsarelistedinTable 3.Insomeinstancesscientisthaveevaluatedtheanti-obesity activity in isolated cell organelles, isolated cellularenzymesspecificallypancreaticlipasearelistedinTables 3 and 4 respectively.Table 4presenttheplantwhichwasstudiedforitsactivityagainstobesityinanin silicomodel.

DiscussionInthisreview,wehavereporttheantiobesityeffectsofdifferentherbal plants or compounds containing minerals or chemicalextractsofplants.PlantshavingreportedantiobesityeffectsarelistedinTable 1withinformationabouttheiractivecomponentsand theireffects. From the review itwas suggested that,plantshowing anti-obesity potential mainly belongs to the familyLeguminoseae,Lamiaceae,Liliaceae,Cucurbitaceae,Asteraceae,Moraceae, Rosaceae and Araliaceae. Majority of the studiesindicatesdecreaseinbodyweightorbodyweightgaininanimalsand humans with or without changes in body fat indicatingantiobesityeffects.Theantiobesityeffectssuchasbodyweightreduction,decreaseinthelevelsoftriglycerides,totalcholesterol,and low density lipoprotein cholesterol with simultaneousincreaseinhighdensitylipoproteincholesterolwasobservedintheanimalstreatedwiththeplants[1,15,29,31,39,54,60,78,79,83,85,98,100,101,133,145,152,165,190,196,201].Inonestudy[41],ithasbeenreportedthatacompoundchakasaponinII,suppressedmRNAlevelsofneuropeptideY(NPY)andenhancedthereleaseof serotonin (5-HT) that suppressed theappetite signals in thehypothalamus of the mice. Clinical trials were conducted onhumans for various plant extracts [45,49,135]which showed asignificantdecreaseinbodyweightandbodyfatreduction.There

Table 1. Anti-obesityeffectofnaturaloccurringplantswithmechanismofactionstudiedonanimalmodelsPlant name Part(s) Mechanism Experimental model Reference

1 Achyranthes aspera Linn(Amaranthaceae)

Seed Theplantlowerstotalcholesterol,totaltriglyceride,andLDL-cholesterol,andincreasesHDLcholesterollevel.

High-fat-fedmaleSwissalbinomice

[24]

2 Acorus calamus Linn(Araceae)

Rhizome,rootsandleaves

EthylacetateextarctofA. calamusinhibitsα-glucosidaseactivity.

Glucosechallengedmice. [25]

3 Achyranthes bidentataBlume(Amaranthaceae)

Root Thedrugaffectsondifferentiationofadipocyteanddecreaseofphospho-Aktexpression.

MaleSprague-Dawleyfedwithahigh-fatdiet

[26]

4 Actinidia polygama Max(Actinidiaceae)

Fruits Serumlevelsofaspartatedecreasedinthemicetreatedwiththeextractwithoutchangesinserumlevelsofalaninetransaminasebloodureanitrogenandcreatinine.

Micewithhigh-fatdietinducedobesity

[27]

5 Adenophora triphylla Hara(Campanulaceae)

Root Anti-obesityeffectofA. triphyllaismediatedbyincreasingadipocytesadiponectinandactivatingpathwaylikeAMPK,andPPAR-α,anddecreasingadipokinesTNF-α,GPDH,andPPAR-α.Italsoactivelyexpresseslow-densitylipoprotein[LDL]receptorandcholestorl7α-hydroxylase(CYA7A1)andinhibitsexpressionof3hydroxy-3methylglutaryl-CoA(HMG-CoA)reductase.

Highfatdiet(HFD)-C57B2/6mice

[28,29]

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6 Aegle marmelos Linn(Rutaceae)

Leaves TheactivechemicalconstituentsofA. marmelosforanti-adipogenicactivityarehalfordinol,ethyletheraegelineandesculetinwereresponsibleforthedecreaseinadipocyteaccumulation.Activecompoundsumbelliferoneandesculetindepleteslipidcontentintheadipocytesandbydecreasingthehyperlipidemia.

HighfatdietinducedobesemaleSpragueDrawlyrat

[30,31]

7 Allium cepa Linn(Amaryllidaceae)

Peel ThemRNAlevelsofactivatingprotein(AP2)isdown-regulatedbyA.cepaandthoseofcarnitinepalmitoyltransferase-1α(CPT-1α)andfattyacidbindingprotein4(FABP4)areup-regulated.ItisalsoproposedthatA. cepa increaseslevelofPPAR-γ2mRNA(mesentericfats)andIL-6mRNAlevels(perirenalandmesentericfats).

Highfat-fedrats,Diet-inducedobeseMaleSprague-Dawleyrats

[32,33]

8 Allium fistulosum Linn(Liliaceae)

Root Significantreductioninbodyweightandadiposetissueweightaswellasadipocytesize.Genesinvolvedinlipogenesisaredown-regulatedbyA. fistulosum.

Highfatdiet-inducedmice [34]

9 Allium nigrum Linn(Amaryllidaceae)

Bulb ExtractofA. nigrumupregulatesAMPK,FOXO1,Sirt1,ATGL,HSL,perilipin,ACO,CPT-1,andUCP1intheadiposetissues,whereasitdownregulatesCD36.

High-fatdietinducedobesemice

[35]

10 Allium sativum Linn(Amaryllidaceae)

Stem,BulbandRoots

Itincreasesantioxidantenzymesandsuppressesglutathionedepletionandlipidperoxidationinhepatictissue.OilisolatedfromA. sativum downregulatessterolregulatoryelementbindingprotein-1c,acetyl-coAcarboxylase,fattyacidsynthase,and3-hydroxy-3-methylglutaryl-coenzymeAreductase.

High-fatdiet-inducedobeseC57BL/6Jmice

[36,37]

11 Alpinia galangaLinn(Zingiberaceae)

Rhizome Galangin,theprincipalcompontentofA. galangal decreasesserumlipids,liverweight,lipidperoxidationandaccumulationofhepaticTGs.

Obesityinducedinfemaleratsbyfeedingcafeteriadiet

[38]

12 Alpinia officinarum Hance(Zingiberaceae)

Root ThedrugcontrolsandimproveslipidprofileinanimalsbyloweringserumTotal-C,TG,andLDL-Cconcentrations,leptincontent.

Obesityinmicefedahigh-fat diet

[39,40]

13 Angelica gigasNakai(Apiaceae)

Roots Decursin,theactiveconstituentofA.gigas improves glucosetolerance.DecursinalongwiththeHFDsignificantlyreducessecretionadipocytokinessuchasleptin,resistin,IL-6andMCP-1.

Micefedahigh-fatdiet [41]

14 Argyreia nervosa Bojer(Convolvulaceae)

Root Serumcontentsofleptin,totalcholestrol,LDL,andtriglyceridesarereducedbyA. speciosa.

Diet-inducedobesityrats [42]

15 Artemisia iwayomogi(Compositae)

WholePlant ItdownregulatesadipogenictranscriptionfactorsPPARγ2andC/EBPαandtheirtargetgenesCD36,aP2,andFAS.TheextractdecreasesgeneexpressionofproinflammatorycytokinesincludingTNFα,MCP1,IL-6,IFNα,andINFβinepididymaladiposetissueandreducesplasmalevelsofTNFαandMCP1.

Micefedahigh-fatdiet. [43]

16 Atractylodes lancea (Thunb.)DC(Compositae)

Rhizome It inhibitshumanpancreaticlipase.Anewpolyacetylene,syn-(5E,11E)-3-acetoxy-4-O-(3-methylbutanoyl)-1,5,11-tridecatriene-7,9-diyne-3,4-diolhasbeenisolatedandidentifiedandexhibitslipaseinhibitoryactivity.

High-fatdiet-inducedobesitymice

[44]

17 Aster pseudoglehni Lim, Hyun & Shin (Asteraceae)

Leaves Itsuppressesexpressionofadipogenesis-relatedgenesincludingPPARγ,C/EBPα,andSREBP1c.

Highfatdietinduced-maleC57BL/6Jmice

[45]

18 Bauhinia variegata Linn(Leguminosae)

Stemandrootbarks

ExtractofE. variegataincreasesbrainserotoninlevelandhigh-densitylipoproteinwithaconcomitantdecreaseintotalcholesterol,triglyceridesandlow-densitylipoprotein.

Hypercaloricdiet-inducedmice

[46]

19 Bergenia crassifolia (L.)Fritsch(Saxifragaceae)

Leaves Galloylbergeninderivatives3,11-Di-O-galloylbergeninand4,11- di-O-galloylbergeninarefoundtobepresentinB. crassifolia moderatesanti-lipidaccumulationactivities.

Ratswithhigh-caloriediet-inducedobesity

[47]

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20 Boehmeria nivea(L.)Gaudich(Urticaceae)

Leaf Theextractsreducesadiposetissueweightserumalkalineaminotransferaseandlactatedehydrogenaseactivities.Serumtriglyceride,totalcholesterol,LDL-cholesterollevel,atherogenicindexandcardiacriskfactorsaredecreasedinanimalsfedwithleafpowderandserumHDL-cholestrollevelsareincreased.

Highfat/cholestroldiet-inducedMaleSprague-Dawleyrats.

[48]

21 Boerhaavia diffusa L.(Nyctaginaceae)

Root ThephytoconstituentscompoundssitosterolfoundinthisplantwhichisstructurallysimilartocholesterolhasbeensuggestedtoreducecholesterolbyloweringthelevelofLDL-cholesterolandcholesterolleveldecreasedsignificantlyinplasmawithoutanysideeffects.

HighfatdietinfemaleSprague-Dawleyrats

[49]

22 Bombax ceiba L.(Malvaceae)

Stembark TheextractandactiveconstituentgemfibrozilreversestheeffectsofHFDtreatmentonserumparameters.Thisactivitymaybeduetotheinactivationofacetyl-coAcarboxylase,asaresultofAMPKactivationthatmediatesthermogenesisandFASinhibition.

Male,Wistaralbinorats [50]

23 Anredera cordifolia (Ten.)Steenis (Basellaceae)

Leaves Theextractsuppresseslipidaccumulationanddown-regulatesPPARγ,CCAAT/enhancerbindingproteinα,SREBP,andtheirtargetgenes.ItalsoincreasesphosphorylationofAMPK.

High-fatdiet-inducedobeserats

[51]

24 Brassica rapa L.(Brassicaceae)

Root Lipolysis-relatedgenesincludingβ3-adrenergicreceptor,hormone-sensitivelipase,adiposetriglyceridelipase,anduncouplingproteinareinducedinwhiteadipocytesofanimalstreatedwithextractofB. campestris.

Highfatdietinducedmice [52]

25 Buddleja officinalis Maxim(Scrophulariaceae)

WholePlant Theextractreducesbodyweightgaininducedthroughadipocytedifferentiation.

High-fatdiettoC57BL/6mice

[53]

26 Bursera grandiflora (Schltdl.)Engl(Burseraceae)

Roots B. grandifloraexertsanti-obesityactivitybydecreasingintheplasma-triglyceridelevels.

MiceoftheC57B1/6strainwithhypercaloricdiet.

[54]

27 Calanus finmarchicus(Calanidae)

Wax C. finmarchicusreducesmacrophageinfiltrationanddownregulatesexpressionofproinflammatorygenesincludingtumornecrosisfactor-α,interleukin–6,andmonocytechemoattractantprotein–1,whereasup-regulatesadiponectinexpression.

C57BL/6Jmicewithhigh-fat diet

[55]

28 Camellia japonica L.(Theaceae)

Leaves C. japonicacontrolinsulinwhichisamodulatoroflipidsynthesisviasterolregulatoryelementbindingprotein-1c(SREBP-1c),decreasedlevelsofinsulinaffectshepatictriglyceridesynthesis.

HighfatdietinducedSprague−Dawleyrats

[56]

29 Camellia oleifera Abel(Theaceae)

Fruithull Serum levels of total cholesterol and triacylglycerols are decreased but high-density lipoprotein cholesterol increased.Activity of fatty acid in animal liver is lowered by.

MaleICRmicewerefedaHFD

[57]

30 Camellia sinensis (L.)Kuntze(Theaceae)

Leaves,twigsandstems,flowerbuds

C. sinesisattenuatesthegeneexpressionof(SREBP-1c),fattyacidsynthaseandCCAAT/enhancerbindingproteinα.ExtractfoundtoreducesICAM-1releasefollowedbynonpharmacologicalHGTEsupplementationindb/dbmicecausingnoadiponectin-inducingorantiadipogeniceffects,reducedsICAM-1release.ChakasaponinIIfromflowerbud,suppressesmRNAlevelsofneuropeptideY(NPY).ThemRNAlevelsofadipogenicgenessuchasPPAR-γ,C/EBP-α,SREBP-1c,adipocytefattyacid-bindingprotein,lipoproteinlipaseandfattyacidsynthasearedecreased in C. Sinensistreatedanimals.

Albinoratsfedonhigh-fatdiet,diet-inducedobesityinFemaleddYmice,highfatinduced-C57BL/6J-Lepob/obmice,highfatdiet-inducedC57BL/6Jmice

[58-64]

31 Cheilanthes albomarginata C.B. Clarke(Pteridaceae)

Rhizome ExtractofC. albomarginatalowersplasmatriglycerideactivityaswellasreducesweightofadiposetissue.

HighfatdietinducedobesemaleSpragueDawleyrats

[65]

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32 Chenopodium quinoa Willd(Amaranthaceae)

Seeds C. quinoaextractattenuatemRNAlevelsofseveralinflammationmarkersincludingmonocytechemotacticprotein-1,CD68andinsulinresistanceosteopontin,plasminogenactivatorinhibitor-1anditalsoreversestheeffectsofHF-induceddownregulationoftheuncouplingprotein(s)mRNAlevelsinmuscle.

Micefedwithstandardlow-fatorahigh-fatdiet

[66]

33 Cirsium brevicaule A. Gray (Compositae)

Leaves C. brevicauleinhibitsfattyacidsynthaseandsuppressthedifferentiationandlipidaccumulationandaffectingtranscriptionfactorssuchasSREBP-1c,C/EBPα,andPPARγknowntocontrolthefattyacidsynthaseexpression.

C57BL/6micethatwerefedahigh-fatdiet

[67]

34 Citrus reticulata Blanco(Rutaceae)

Peel mRNAexpressionlevelsoflipogenesisrrelatedgenessuchasSREBP1c,FASandACC1intheliverareloweredandthesizeofadipocytesarereduced.


35 Citrus sunki (Hayata)Yu.Tanaka(Rutaceae)

Peel PhosphorylationlevelsofAMPKandacetyl-CoAcarboxylasearedecreased.

High-fatdietinducedobeseC57BL/6mice

[69]

36 Clerodendrum phlomidis L.f.(Lamiaceae)

Roots Itnhibitspancreaticlipaseactivity.Theextractcontainsβ-sitosterol.

HighfatdietinducedobesityinC57BL/6Jmice

[70]

37 Coccinia grandis (L.)Voigt(Cucurbitaceae)

Fruit Reducesbodyweight,foodintake,organandfatpadsweightandserumGLU,CHO,TRG,LDLandVLDLcholesterollevelsandincreasesHDLlevels.

Cafeteria diet and Atherogenicdietinducedobesityinfemalerats.

[71]

38 Codonopsis lanceolata (Siebold&Zucc.)Benth.&Hook.f.exTrautv(Campanulaceae)

Roots Reducesweightofadiposepadsandtheserumlevelsoftriglycerides,totalcholesterol,andlowdensitylipoproteincholesterol.

High-calorie/high-fat-dietinducedobesitySprague-Dawleymalerats

[72]

39 Coffea arabica L.(Rubiaceae)

Seed C. arabicadietsupplementationcanimpairglucosetolerance,hypertension,cardiovascularremodeling,andnonalcoholicfattyliverdisease.

High-carbohydrate,high-fatdiet-fedWistarmalerats

[73]

40 Coleus forskohlii (Willd.)Briq.(Lamiaceae).

Root C. forskohliiactasanti-obesisitydrugbyinhibitingdyslipidemia.

Diet-inducedobesityinrats [74,75]

41 Corchorus olitorius L.(Malvaceae)

Leaves Livertissuegeneexpressionofgp91phox(NOX2)involvedinoxidativestressisdown-regulatedbyC. olitorius and genesrelatedtotheactivationofβ-oxidationlikePPARαandCPT1Aareup-regulatedbytheplant.

Highfatdiet-inducedLDLreceptordeficientmice

[76]

42 Cordia ecalyculata Vell(Boraginaceae)

Wholeplant Anti-obesityactivityoftheC. ecalyculata ismedicatedbyanorecticcentralaction,facilitatingbindingtoadenosinereceptors,therebypromotinganextensionofadrenalin.

Mice(albino,swissstrain)treatedwithcyclophosphamide

[77]

43 Cornus officinalis Siebold&Zucc.(Cornaceae)

Rhizome PlatycodinDisthemajorcomponenteffectivetoactivateAMPK-α.Theextractreducesserumlevelsofaspartatetransaminaseandalaninetransaminase.

C57BL/6JmicewerefedaHFdiet

[78]

44 Cucumis melo L.(Cucurbitaceae)

Fruitpeel C. meloreducesgaininbodyweight,serumlipidprofileliketotalcholesterol,triglyceride,LDL-Clevel,atherogenicindexandincreasesserumHDL-Clevels.

Highcholesteroldietinducedinrats

[79]

45 Cyamopsis tetragonoloba (L.)Taub(Leguminosae)

Beans Itdecreasesadiposetriglycerideaccompaniedbyenhancingactivityofhormone-sensitivelipase-facilitatingmobilizationofdepotfat.

High-fat-fedWistarrats [80]

46 Dimocarpus longans Leenh(Sapindaceae)

Flower Bycombinedeffectofdecreasedexogenouslipidabsorption,normalizationofhepaticPPAR-γgeneexpression,suppressionofpancreaticactivityandSREBP-1candFASgeneexpression,andhigherfecaltriglycerideoutput.

Hypercaloricdiet-maleSprague-Dawleyrats.

[81]

47 Dioscoreae tokoronis Linn(Dioscoreaceae)

Root Itdecreasestriglyceride,totalplasmacholesterol,andlow-densitylipoprotein-cholesterol.ItsuppressestheexpressionofSREBP-1aswellasthatoffattyacidsynthaseinadiposeandlivertissues.


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48 Eucommia ulmoides Oliv(Eucommiaceae)

Leaves,Bark Asperulosideincreasesadenosine5′-triphosphateproductioninWATandincreasesuseofketonebodies/glucoseinskeletalmuscle.

ObesityinducedbyovariectomyinfemaleWistarrats,ratsfedahigh-fat diet.

[83,84]

49 Fraxinus excelsior L.(Oleaceae)

Seed Secoiridoidspresentenhancesfatmetabolismthroughβ-oxidation,inhibitadipocytedifferentiationduringanimalgrowthandlimitfataccumulation.


50 Garcinia cowa Roxb.ex Choisy(Clusiaceae)

Fruit,commerciallyavailabletablet

InhibitstheenzymeATP-dependentcitratelyase,whichcatalyzesthecleavageofcitratetooxaloacetateandacetyl-CoA.SerumapoA1levelsareincreasedbytheplantandtheserumtotalcholesterollevels.

FemaleSprague-Dawleyratsfedatherogenicdiet

[86,87]

51 Geranium thunbergiiSieboldexLindl.&Paxton(Geraniaceae)

Leaf Theextractameliorateshigh-fatdiet-inducedobesitybyalteringtheadipokinelevelsanddownregulatesexpressionoftranscriptionfactorsandlipogenicenzymesinvolvedinlipidmetabolism.


52 Glycine max (L.)Merr.(Leguminosae)

Bean Reductionsglucose-6-phosphatedehydrogenase,malicenzyme,fattyacidsynthetase,aswellasacetyl-CoAcarboxylase.TheextractdecreasesappetiteandHFdiet-inducedbodyweightgainthroughleptin-likeSTAT3phosphorylationandAMPKactivation.

Diet-inducedobesemice [89,90]

53 Gymnema sylvestre (Retz.)R.Br.exSm(Apocynaceae)

Leaves Inhibitsserumlipids,leptin,insulin,glucose,apolipoproteinBandLDHlevelswhileitincreasestheHDL-cholesterol,apolipoproteinA1andantioxidantenzymeslevels.

Highfatdiet-inducedobesityinwistarrats

[91-93]

54 Hibiscus cannabinus L.(Malvaceae)

Leaves Itdecreasesserumcholesterol,triglycerides,LDL-C,SGOTandSGPTactivities.

Highcholesteroldietinducedobesityinfemalealbinorats

[94]

55 Hibiscus sabdariffa L.(Malvaceae)

Leaf PromotesLXRα/ABCA1pathway,stimulatingcholesterolremovalfrommacrophages,delayingatherosclerosis.Also,theextracttreatmentattenuatedliversteatosis,downregulatedSREBP-1candPPAR-γ,blockedtheincreaseofIL-1,TNF-αmRNAandlipoperoxidationandincreasedcatalasemRNA.

Highfatdiet-inducedobeseC57BL/6NHsdmice

[95,96]

56 Holoptelea integrifolia (Roxb.)Planch.(Ulmaceae)

Bark HMG-CoAreductaseactivityisreducedandcholesterolbiosynthesisandincreaseinlecithin,cholesterolacyltransferaseactivity.

Diet-inducedobeserat [97]

57 Humulus lupulus L.(Cannabaceae)

Femaleinflorescence

HepaticfattyacidsynthesisisreducedthroughthereductionofhepaticSREBP1cmRNAexpressionintheratsfedahigh-fatdiet.

High-fatdietinducedobeserat,maleC57BL/6JmicefedaHFdiet

[98,99]

58 Hunteria umbellata (K.Schum.)Hallierf.(Apocynaceae)

Seed Theextractreducesweightgainpatternandcausesdoserelatedreductionsintheserumlipids,Coronaryarteryriskindex.Also,pre-treatmentsignificantlyimprovestriton-inducedhepatichistologicallesions.

Highfatdiet-inducedrats [100]

59 Hypericum philonotisSchltdl.&Cham.(Hypericaceae)

Leaves Decreasesbodyweightandserumglucoselevels.Italsodecreasestotalcholesterol,triglyceridesandhigh-densitylipoprotein-cholesterolwithoutchanginglow-densitylipoprotein-cholesterol,AI,ASTandALTlevel.

MaleWistarratsfedwithhighfatdiet

[101]

60 Hypericum silenoides Juss.(Hypericaceae)

Leaves Bodyweightandserumglucoselevelsoftheratsdecreased.Thedrugalsohaseffectontotalcholesterol,triglyceridesandhigh-densitylipoprotein-cholesterol.

MaleWistarratsfedwithhighfatdiet

[101]

61 Ilex paraguariensisA.St.-Hil.(Aquifoliaceae)

Leavesandunripefruits

Down-regulatesexpressionofCreb-1andC/EBPa,andup-regulatesexpressionofDlk1,Gata2,Gata3,Klf2,Lrp5,Pparc2,Sfrp1,Tcf7l2,Wnt10b,andWnt3a.ThemRNAlevelsofPPAR-γ2weredownregulated.

Highfatdiet-inducedmice,maleWistarratsfeddiet

[102-105]

62 Ipomoea batatas (L.)Lam(Convolvulaceae)

Fruit ExpressionofSREBP-l,Acyl-CoASynthase,Glycerol-3-PhosphateAcyltransferase,HMG-CoAReductaseandFattyAcidSynthaseinlivertissueinmiceisaltered.

Micefedwithhigh-fatdiet [106]

63 Saccharina japonica(Phaeophyceae)

WholePlant Expressionofthefatintake-relatedgeneACC2andlipogenesis-relatedgenesarereduced.ItincreasesphosphorylationofAMPKanditsdirectdownstreamprotein,acetylcoenzymeAcarboxylase.

High-fat-diet-inducedobesemaleSprague-Dawleyrats

[107,108]

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64 Larix laricina(DuRoi)K.Koch(Pinaceae)

WholePlant Stimulatesglucoseuptake,potentiatedadipogenesis,activatedAMPK,andactedasmitochondrialuncoupler/inhibitor(onnormalisolatedmitochondria).

Diet-inducedobeseC57BL/6mice

[109]

65 Ligularia fischeri (Ledeb.)Turcz.(Compositae)

Leaves Polyphenolspresentintheextractexhibitsantiobesityeffectsbyinhibitingpancreaticlipase.

C57BL/6mice [110]

66 Ligustrum lucidum W.T.Aiton(Oleaceae)

Fruits TreatmentwiththeextractdecreasesHFD-inducedobesity,mainlybyimprovingmetabolicparameters,suchasfatsandtriglycerides.

Highfat-diet-inducedC58BL/6Jobesemice

[111]

67 Lithocarpus polystachyus (Wall.exA.DC.)Rehder(Fagaceae).

Leaves Decreaseslevelsofserumlipids,attenuatesbodyweightgainandlowerscirculatingleptinandinsulinlevels,amelioratethestateofoxidativestress,raiseserumadiponectin,reducecirculatingCRPandresistinlevels,anddepressesexpressionofPPARγandC/EBPα.

Highfatdiet-inducedobeserats

[112]

68 Lithospermum erythrorhizon Siebold&Zucc.(Boraginaceae)

Roots Reduceshigh-fatdiet-inducedincreasesinbodyweight,whiteadiposetissuemass,serumtriglycerideandtotalcholesterollevels,andhepaticlipidlevelsanddecreaseslipogenicandadipogenicgeneexpression.Acetylshikonin,activeconstituentofL. erythrorhizonsuppressesadipocytedifferentiationandattenuatesadipogenictranscriptionfactorexpression.

C57BL/6Jmicewerefedanormalorhigh-fatdiet

[113,114]

69 Morinda citrifolia L.(Rubiaceae)

Fruit Reducesbodyweightandfatmass.Itincreasesglucosetoleranceandreducedplasmatriglycerideslevel.

High-fatdiet-inducedobesityinmice

[115]

70 Morus alba L.(Moraceae)

Fruit,leaves ThehepaticperoxisomePPAR-Randcarnitinepalmitoyltransferase-1areelevated,whilefattyacidsynthaseand3-hydroxy-3-methylglutaryl-coenzymeA(HMG-CoA)reductasearereduced.Itdecreaseshepaticlipids,fattyacidsynthaseand3-hydroxy-3-methylglutaryl-coenzymeA(HMG-CoA)reductaseandelevateshepaticperoxisomePPAR-αandcarnitinepalmitoyltransferase-1.

Highfatdiet-inducedmice,6-week-oldmalehamsters.

[116]

71 Morus australis Poir(Moraceae)

Fruit Reducesresistancetoinsulin,associatedwithleptin. MaleC57BL/6micefedwithhigh-fatdiet

[117]

72 Morus nigra L.(Moraceae)

Fruit,leaves, ProinflammatorycytokinesMCP-1andTNF-α,plasmatriglyceride,liverlipidperoxidationlevelsandadipocytesizearedecreased.Inflammatorymarkers(monocytechemoattractantprotein-1,induciblenitricoxidesynthase,C-reactiveprotein,tumournecrosisfactor-αandinterleukin-1)inliverandadiposetissueareincreased.

Adenovirus36-inducedobesityinmice,high-fat(HF)diet-inducedobesemice.

[116-120]

73 Murraya koenigii(L.)Spreng.(Rutaceae)

Leaves Reducesbodyweightgain,plasmatotalcholesterolandtriglyceridelevelsinmice.


74 Myrciaria dubia (Kunth) McVaugh(Myrtaceae)

Fruit Reducesanimalbodyweightsofthefatinwhiteadiposetissues,glucose,totalcholesterol,triglycerides,andLDL-candinsulinbloodlevels.AnincreaseinHDL-clevelsalsoseen.

Wistarratswithobesityinducedbysubcutaneousinjectionofmonosodiumglutamate

[122]

75 Myrtus communis L.(Myrtaceae)

Leaves Thebodyweightreducedby32%whenadministeredwithsibutramine,whileitwasreducedby21%and24%whenadministeredwiththemethanolicextractofM. communis/kgbodyweight.


[123]

76 Nelumbo nucifera Gaertn.(Nelumbonaceae)

Seedepicarp,leaves,seed,petals

Theextractseffectiveininhibitingpreadipocytedifferentiation.Theflavonoidsinhibitseffectonbothadipocytedifferentiationandpancreaticlipaseactivity,accumulationanddecreasesexpressionPPARγ,GLUT4,andleptininculturedhumanadipocytes,indicatingthatitinhibitsthedifferentiationofpre-adipocytesintoadipocytes.Themethanolextractinhibitslipaseactivityandsuppressestheexpressionoffattyacidsynthase,acetyl-CoAcarboxylase,andHMGCoAreductaseandincreasesthephosphorylationofAMP-activatedproteinkinaseintheliver.

Highfatdiet-inducedmiceMaleSprague-Dawleyratswerefedwithanormaldietandahigh-fatdiet,Highfatdiet-inducedC57BL/6mice.

[124-127]

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77 Nephelium lappaceum L.(Sapindaceae)

Fruit TheexpressionofIgf-1andIgf-1RwerereducedonobeseratmodeltreatedwithextractofN. lappaceum.

Ratfedwithhighcaloriedietandtreatedwithellagicacid

[128]

78 Nitraria retusa (Forssk.)Asch.(Nitrariaceae)

Shoot Theextractsupressesincreaseinbodyandfatmassweight,anddecreasestriglyceridesandLDL-cholesterollevelsandenhancesgeneexpressionrelatedtolipidhomeostasisinlivershowinganti-obesityactions.

BKS.Cg-Dock7m+/+Leprdb/Jmicemodel

[129]

79 Olea europaea L.(Oleaceae)

Leaves TheextractreversesHFD-inducedupregulationofWNT10b-andgalanin-mediatedsignalingmoleculesandkeyadipogenicgenes(PPARγ,C/EBPα,CD36,FAS,andleptin).Italsoinducesdownregulationofthermogenicgenesinvolvedinuncoupledrespiration(SIRT1,PGC1α,andUCP1)andmitochondrialbiogenesis(TFAM,NRF-1,andCOX2).

High-fatdiet-inducedobesityinmice

[130,131]

80 Orthosiphon aristatus (Blume)Miq(Lamiaceae)

Wholeplant Betulinicacid,theactiveconstituentsuppresseshypothalamicproteintyrosinephosphatase1Binmiceandenhancestheantiobesityeffectofleptininobeserats

High-fat-fedmice [132]

81 Panax ginseng C.A.Mey.(Araliaceae)

Root GinsamincreasesPPAR-γexpressionandAMP-activatedproteinkinasephosphorylationinliverandmuscle.TheextractsstronglyactivatesHormoneSpecificLipaseviaProteinKinaseA.

Insulin-resistantrat,highfatdietinducedobeseC57BL6/Jmice

[133,134]

82 Perilla frutescens (L.)Britton(Lamiaceae)

Leaf Itdecreasesbodyweightgain,foodefficiencyratio,andrelativeliverandepididymalfatmass.

Highfatdiet-inducedrats [135]

83 Petasites japonicus (Siebold&Zucc.)Maxim.(Compositae)

Flowerbuds Theextractsattenuatethreeadipogenetictranscriptionfactors,peroxisomePPAR-γ2,CCAAT/enhancer-bindingproteinandsterolregulatoryelement-bindingprotein1c.

Diet-inducedobesity-prone mice.

[136]

84 Phaseolus vulgaris L.(Leguminosae)

Bean Itreducesfoodintakeandbodyweightinananimalmodelofobesityresultinginsuppressionofglycaemia.

GeneticallyobeseadultmaleZuckerfa/farats.

[137]

85 Phyllostachys edulis (Carrière)J.Houz.(Poaceae)

Leaves TheextractameliorateselevatedMCP-1concentrationintheblood.

Highfatdiet-inducedC57BL/6Jmice

[138]

86 Pinus koraiensis Siebold&Zucc(Pinaceae)

Leaves Suppressesfataccumulationandintracellulartriglycerideassociatedwithdownregulationofadipogenictranscriptionfactorexpression,includingPPARγandCEBPαinthedifferentiated3T3-L1adipocytes.ItattenuatesexpressionofFABPandGPDHastargetgenesofPPARγduringadipocytedifferentiation.

HighfatdietMaleSprague-Dawleyrats

[139]

87 Piper fragile Benth(Piperaceae)

Seed P. fragilerudeoilshowssignificantreductioninbodyweight.

MaleSpraguedawleymiceweretreatedwithhighcholesteroldiet

[140]

88 Piper sarmentosum Roxb.(Piperaceae)

leaves P. sarmentosumgroupshowsreductioninenzymeactivity.AqueousextractofP. fragilehavetheabilitytoreduce11β-HSD1enzymeactivity.

Ovariectomy-InducedObeseRats

[141]

89 Platycodon grandiflorum(Campanulaceae)

Roots Platycodinfeedingincreasescholesterolabsorptionupto60%,butnotcholesterolsynthesis.Platycodin-enricheddietscanlowercirculatingandwholebodycholesterolcontents.

GoldenSyrianhamsters [142]

90 Polygonum aviculare L.(Polygonaceae)

AerialParts ExtractofP. avicularesuppressestheelevatedmRNAexpressionlevelsofsterolregulatoryelement-bindingprotein-1c,peroxisomePPAR-γ,fattyacidsynthase,andadipocyteprotein2inthewhiteadiposetissueofobesemice.


[143]

91 Populus balsamifera L.(Salicaceae)

WholePlant Salicortinreduceswholebodyandretroperitonealfatpadweights,aswellashepatictriglycerideaccumulation.Italsomodulateskeycomponentsinsignalingpathwaysinvolvedwithglucoseregulationandlipidoxidationintheliver,muscle,andadiposetissue.

C57Bl/6micesubjectedtohighfatdiet

[144]

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92 Premna integrifolia Linn(Verbenaceae)

Roots Asignificantdecreaseinthelevelsofserumglucose,triglyceride,totalcholesterol,LDLandVLDLobservedintheanimalstreatedwiththeextractofP. integrifolia.

FemaleSwissAlbinomice,fedwithcafetariadiet

[145]

93 Prunus mume (Siebold)Siebold&Zucc(Rosaceae)

Fruit IncreasesCPT-1expressionanddecreasesFAS,ACC,andSREBP-1cintheliverandquadricepsmusclestoresultinginreducingtriglycerideaccumulation.ItalsoimprovesinsulinsensitivityinOVXratsandpreventstheimpairmentofenergy,lipid,andglucosemetabolismbyOVXthroughpotentiatinghypothalamicleptinandinsulinsignaling.

Highfatdiet,ovariectomizedrats

[114]

94 Pueraria montana var.chinensis(Ohwi)Sanjappa&Pradeep(Leguminosae)

Flower Itdownregulatesacetyl-CoAcarboxylaseexpression.Foradiposetissue,theexpressionsofhormone-sensitivelipaseinwhiteadiposetissueanduncouplingprotein1inbrownadiposetissueareupregulated.

MaleC57BL/6Jmicewerefedahigh-fatdiet

[146]

95 Punica granatum L(Lythraceae)

Leaves,seed PunicicacidbindsandactivatesPPAR-αandγ,thusupregulatingPPARαanditsresponsivegenes(Stearoyl-CoAdesaturase-1,SCD1;Carnitinepalmitoyltransferase1,Cpt-1;andacyl-coenzymeAdehydrogenase)aswellasPPARγ-responsivegenesexpression(CD36andFattyAcidBindingProtein4,FABP4)inintra-abdominalwhiteadiposetissuewhilesuppressingexpressionoftheinflammatorycytokineTNF-αandNF-κBactivation.


[147,148]

96 Rheum palmatum L.(Polygonaceae)

Root ItinhibitsperoxisomePPAR-γtransactivityandtheexpressionofitstargetgenes,suggestingthatrheinactsasaPPARγantagonist.

Diet-inducedobesefemaleC57BL/6mice

[108,149,150]

97 Rosmarinus officinalis L.(Lamiaceae)

Leaves Itdecreasescirculatingtumornecrosisfactoralpha,IL-1β,andleptin,andupregulatedadiponectin.TheextractalsoinducesphaseIandphaseIIgeneexpressionandtheperoxisomePPAR-γcoactivator1-alpha.Serumtriglycerides,cholesterolandinsulinlevelsarealsodecreasedintheleananimals.

Lean(Le,fa/+)andobese(Ob,fa/fa)femaleZuckerrats

[151]

98 Rubus fruticosus L.(Rosaceae)

Fruit Purifiedblueberryanthocyaninshavebeenshowntoimprovebodyweightandbodycompositionandreduceobesityinmice.

C57BL/6J micefedahigh-fatdiet

[152]

99 Sapindus emarginatus Vahl(Sapindaceae)

Pericarpofflower

Methanolicextractdecreasesbodyweight,BMI,Bloodglucoselevels,totalcholesterol,LDL-C,HDL-C,Triglycerides,SGOT,andSGPT.

Monosodiumglutamateinducedobesityinwistaralbinorats

[153]

100 Sasa quelpaertensis Nakai(Poaceae)

Leaves AdipogenesisisinhibitedbythisdrugbydownregulatingtheexpressionofCCAAT/enhancer-bindingproteinα,peroxisomePPAR-γ,SREBP-1c,andaP2.ItalsodecreasestheexpressionoffattyacidsynthaseandadiponectinmRNAsindifferentiatingadipocytes.ItincreasesAMPKandacetyl-CoAcarboxylasephosphorylation.

High-fatdiet-inducedobeseC57BL/6mice

[154,155]

101 Schisandra chinensis (Turcz.)Baill.(Schisandraceae)

Peel ItdecreasesexpressionofC/EBPβ,C/EBPαorPPARγ,andresultantdown-regulationoftheterminalmarkergene,aP2duringdifferentiationof3T3-L1preadipocytesintoadipocytes.AktandGSK3βphosphorylationaredown-regulatedblockingadipogenesisandadipocytedifferentiation.

HFD-inducedobeserats [156]

102 Senna siamea (Lam.) H.S.Irwin & Barneby(Leguminosae)

Roots Activeconstituentsincludeschrysophanol,physcion,emodin,cassiaminA,friedelinandcycloart-25-en-3,24-diolexhibitspancreaticlipaseinhibitoryactivity.

Alloxaninduceddiabetesrats.

[157]

103 Shorea robusta Gaertn(Diptercarpaceae)

Leaves Itdecreasesserumglucose,triglyceride,cholesterol,LDL-C,HDL-C,VLDL-C,atherogenicindex,SGPTandSGOT.

Monosodiumglutamateinducedobesityinalbinorats

[158]

104 Sida rhombifolia L. (Malvaceae)

Leaf Up-regulationofPPARγ2andSREBP-1cexpressionintheepididymaladiposetissue,leadingtoattenuationofadipogenesis.

Highfatdiet-inducedC57BL/6Jmice

[159]

105 Solanum lycopersicum L.(Solanaceae)

Fruit AMP-activatedproteinkinaseandacetyl-CoAcarboxylasephosphorylationinliveriselevated,andHMG-CoAreductaseexpressionisdecreased.ItstronglydecreasesexpressionofperoxisomePPAR-γ,CCAAT/enhancer-bindingproteinalphaandperilipinintheadiposetissue.

High-fat-diet-inducedobesityinC57BL/6mice

[160,161]

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106 Syzygium aromaticum (L.)Merr.&L.M.Perry(Myrtaceae)

Flowerbuds Theextractsuppressesexpressionoflipidmetabolism-relatedproteins,includingSREBP-1,FAS,CD36andPPARγintheliverandWAT,inadditiontodownregulatesmRNAlevelsoftranscriptionfactorsincludingSREBPandPPAR-γ.

Highfatdietfedmice [162]

107 Tamarindus indica L.(Leguminosae)

Fruitpulp,pulp,seed coat

Levelsofplasmatotalcholesterol,lowdensitylipoprotein,andtriglycerideisdecreasedanditincreaseshigh-densitylipoprotein,withtheconcomitantreductionofbodyweight.

Diet-inducedobeseSprague-Dawleyrats

[163-165]

108 Tecomella undulata (Sm.)Seem.

Bark TheextractshowsasignificantincreaseinSIRT1andadiponectinlevelsanddecreaseinPPAR,C/EBP,E2F1,leptinandLPLlevelsinpreadipocytesandadipocytesandshowsimprovementinlipidprofileandglucoselevels.

HighFatDietobesemice. [166]

109 Vaccinium corymbosum L.(Ericaceae)

Peel ItinhibitslipidaccumulationanddecreasesexpressionofC/EBPβ,aswellastheC/EBPαandPPARγgenesduringthedifferentiationofpreadipocytesintoadipocytes.Itdown-regulatesadipocyte-specificgenessuchasaP2andFAS.

High-fatdiet-inducedobeserats

[167]

110 Veratrum nigrum L.(Melanthiaceae)

Wholeplant Itreducesweightgainandthefatpadweightinhighfatdiet-inducedobesemice.

High-fatdiet-inducedobesemice

[134]

111 Vigna angularis (Willd.)Ohwi&H.Ohashi(Leguminosae)

Seed Itreducestotalhepaticlipidaccumulationandlipidsecretionintothefeces.Incubationofadipocyteswiththeextractsignificantlydecreasestriglycerideaccumulation,glycerolphosphatedehydrogenaseactivityandinflammatoryresponseswithoutaffectingcellviability.

Highfatdiet-inducedobesityinrats

[168]

112 Vigna nakashimae

(Ohwi)Ohwi&H.Ohashi(Leguminosae)

Seeds Itdecreasesexpressionofperoxisomeproliferatoractivatedreceptorγanditstargetgenes.ItenhancesthephosphorylationofAMP-activatedproteinkinase(AMPK)andacetylCoAcarboxylase(ACC),andincreasestheexpressionoffattyacidoxidationgenes.

High-fatdietfedmice [169]

113 Viscum album L.

(Santalaceae)

Leaves,stems,

andfruits

Bodyandepididymalfatpadweightsare,andhistologicalexaminationindicatesanameliorationoffattyliver.Itpotentlyinducesmitochondrialactivitybyactivatingthermogenesisandimprovingendurancecapacityandalsoinhibitedadipogenicfactorsinvitro.

MaleC57Bl/6micefeda

high-fatdiet

[170]

114 Vitis thunbergiiSiebold&Zucc(Vitaceae)

Roots ActivationofAMPKactivatingglucoseandlipid

metabolism.

High-fatdiet-fed

C57BL/6JNarlmice

[171]

115 Vitis vinifera L.

(Vitaceae)

Seedflours,

peel,roots,fruit

Byup-regulatinghepaticgenesrelatedtocholesterol(CYP51)andbileacid(CYP7A1)synthesisaswellasLDL-cholesteroluptake.Lipidmetabolism-associatedgenesMlxp1,Stat5a,Hsl,Plin1,andVdrweredown-regulated.TheextracttreatmentdecreasesexpressionofaP2,Fas,andTnfa,knownmarkersofadipogenesis,asmeasuredbyreal-timepolymerasereaction.ExpressionofPPAR-γinliverandadiposetissueisloweredbyregulatingthelipidmetabolismandsuppressedobesity.

MaleGoldenSyrian

hamstersfedhigh-fat(HF)diets,highfatdiet-inducedC57BL/6Jmice

[54,171-

178]

116 Zanthoxylum bungeanum Maxim.(Rutaceae)

Fruit Itreducesweightgain,whiteadiposetissuemass,andserumtriglycerideandcholesterollevels.ItalsodecreasedlipidaccumulationandPPARγ,C/EBPα,SREBP-1,andFASproteinandmRNAlevelsintheliver.

ObeseC57BL/6micefeda

high-fatdiet

[179]

117 Ziziphus mauritiana Lam(Rhamnaceae)

Bark Itreducesbodyweight,fatmassandpancreaticlipase

activity.

HighFatDietinduced

obesityinWistarrats

[180]

118 Dohaekseunggi-tang

traditionalplant-basedmedicine(TaoheChengqiTang:Chinese)

Commercial

formula

Dohaekseunggi-tangconsistsoffiveherbsincludingGlycyrrhizae uralensisFischer(40g),Rheum undulatumLinne(80g),Prunus persicaLinne(60g),Cinnamomum cassiaPresl(40g),andNatriiSulfas(40g)mixed.Theextractdecreasedserumtotalcholesterol,LDL-cholesterol,triglyceride,glucose,andleptinconcentrations,andincreasedHDL-cholesterolandadiponectinlevelsandincreasedmRNAexpressionofperoxisomeproliferatoractivatedreceptor-γ,uncouplingprotein-2,andadiponectininvisceraladiposetissueofHFDmice

High-fatdietinducedobese

mice

[181]

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Table 2. Anti-obesityeffectofplantswithmechanismofactionstudiedoncelllineasmodel.1 Acorus calamus Linn

(Araceae)Rhizome,rootsandleaves

EthylacetateextractofA. calamusinhibitsα-glucosidaseactivity.

HTT-T15cellline [25]

2 Aegle marmelos Linn(Rutaceae)

Leaves Activecompoundsumbelliferoneandesculetindepleteslipidcontentintheadipocytesandbydecreasingthehyperlipidemiainobeseratsfedwithhigh-fatdiet.

3T3-L1preadipocytes [30,31]

3 Agrimonia pilosa Ledeb(Rosaceae)

Aerialparts Activeconstituent1beta-hydroxy-2-oxopomolicacidinhibitsadipocytedifferentiationandexpressionofadipogenicmarkergenes,suchasPPAR-γ,C/EBPalpha,GLUT4,adiponectin,aP2,ADD1/SREBP1c,resistin,andfattyacidsynthase.ItalsoinhibitsadipocytedifferentiationthroughdownregulationofvariousadipocytokinesbyblockingPPAR-γandC/EBPalphaexpression.

3T3-L1preadipocytes [182]

4 Alnus hirsuta (Spach)Rupr.(Betulaceae)

Leaves Platyphyllonol-5-O-β-d-xylopyranosidesuppressestheinductionofPPARγandC/EBPαproteinexpression,andinhibitsadipocytedifferentiation.

3T3-L1preadipocytecells [183]

5 Amomum cardamomum L.(Zingiberaceae)

Seeds ByregulatingtheC/EBPα,C/EBPβandPPARγgeneand protein expressions.

3T3-L1Celllines. [184]

6 Bauhinia variegate L.(Fabaceae)

Flowers,flowerbuds,stem,roots,stembark,seeds,leaves

itreducesincreasedleveloftotalcholesterol,triglycerides,LDLPandincreasesthelevelofHDLP,brainserotoninlevel.β-sitosterolinthesteminducessecretionofserotonininbrainandinturnexhibitsanti-obesityactivity.

Humanneutrophils. [185]

7 Brassica rapa L.(Brassicaceae)

Root Lipolysis-relatedgenesincludingβ3-adrenergicreceptor,hormone-sensitivelipase,adiposetriglyceridelipase,anduncouplingproteinareinducedinwhiteadipocytesofanimalstreatedwithextract of B. campestris.ActivationofcyclicAMPK,HSL,andextracellularsignal-regulatedkinaseareinducedinEBR-treated3T3-L1cells.

3T3adipocytes. [52]

8 Caesalpinia sappan L.(Leguminosae)

Heartwood Brazileininhibitsintracellularlipidaccumulationduringadipocytedifferentiationin3T3-L1cellsandsuppressestheinductionofperoxisomePPAR-γ(PPARγ).

Postconfluent3T3-L1preadipocytes

[186]

9 Citrus aurantium L.(Rutaceae)

Fruits,leaves ItinhibitsAktactivationandGSK3βphosphorylation,whichinducesthedown-regulationoflipidaccumulationandlipidmetabolizinggenes,ultimatelyinhibitingadipocytedifferentiation.

3T3-L1preadipocytes [22,187,188]

10 Coptis chinensisFranch.(Ranunculaceae)

Rhizome Itinhibitslipidaccumulationin3T3-L1cells.ThefivealkaloidspresentinthisplantsignificantlyreducesexpressionlevelsofseveraladipocytemarkergenesincludingproliferatoractivatedreceptorandCCAAT/enhancer-bindingprotein.Isolatedalkaloidsfoundtoinhibitadipogenesis.

3T3-L1adipocytescells [189]

11 Cucurbita moschata Duchesne(Cucurbitaceae)

Stems ReducesexpressionofperoxisomePPAR-γ,CCAAT/enhancer-bindingproteinα,fattyacid-bindingprotein4,sterolresponseelement-bindingprotein-1candstearoyl-coenzymeAdesaturase-1,anddecreaseslipidaccumulation.

Primarymouseembryonicfibroblasts

[190]

12 Curcuma longa L.(Zingiberaceae)

Rhizomes Increasehormone-sensitivelipaseandadiposetriglyceridelipasemRNAlevelsanddecreasesperilipinmRNAlevelviaAMPK,resultinginlipolysis.Inadiposetissue,curcumininhibitsmacrophageinfiltrationandnuclearfactorκBactivationinducedbyinflammatoryagents.

3T3-L1adipocytes [191,192]

13 Cyclopia falcata (Harv.)Kies(Leguminosae)

Stem Flavonoid,phloretin-3′,5′-di-C-glucosideinhibitsintracellulartriglycerideanddownregulatesPPAR2expression and in in vitro conditionitcaninhibitadipogenesis.

3T3-L1mousepre-adipocytes

[193]

14 Cyclopia maculata (Andrews)Kies(Leguminosae)

Stems Mangiferin,hesperidininhibitsintracellulartriglycerideandfataccumulation,anddecreasesPPAR2expressionandinin vitroitcaninhibitadipogenesis.

3T3-L1mousepre-adipocytes

[193]

12



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15 Dalbergia sissoo DC.(Leguminosae)

Leaves Inhibitspancreaticlipaseandcanbeusedasananti-obesityagentinsuitableform.

Chickenpancreas [194]

16 Dioscorea oppositifolia L.(Dioscoreaceae)

Rhizome DecreasesexpressionofPPAR-γ.BatatasinIcompoundfromtheextractwasfoundtoincreasep-AMPKandCPT-1in3T3-L1adipocytes,resultingininhibitingadipogenesis.

Mouseembryopreadipocyte(3T3-L1)celllines

[195]

17 Eremochloa ophiuroides(Munro)Hack(Poaceae)

WholePlant ExpressionofC/EBPandPPAR,thecentraltranscriptionalregulatorsofadipogenesis.Moreover,thisplantdown-regulatesphosphorylationlevelsofAktandGSK3.

Mouse3T3-L1preadipocytes

[196]

18 Glycine max (L.)Merr.(Leguminosae)

Bean Itinhibitsadipocytedifferentiationin3T3-L1preadipocytecells.AccumulationoftriglyceridesisinhibitedandactivationofAMPK.

3T3-L1 preadipocytecells

[89,90]

19 Houttuynia cordata Thunb.(Saururaceae)

Leaf Attenuatesexpressionoffattyacidsynthase,sterolregulatoryelement-bindingprotein-1andglycerol3-phosphateacyltransferases.TheextractinhibitstheelevationofplasmaTGlevelsinmice.TheextractspossiblysuppresstheuptakeofNEFAandglycerolbyblockingFAT/CD36andalsosuppressaquaproin-7.

HumanHepG2hepatocytes

[197,198]

20 Ilex paraguariensisA.St.-Hil.(Aquifoliaceae)

Leavesandunripefruits

AmodulatoryeffectontheexpressionofgenesrelatedtotheadipogenesisasPPAR2,leptin,TNFandC/EBParealsoseen.

3T3-L1cellline [102-105]

21 Ipomoea batatas (L.)Lam(Convlvulaceae)

Fruit ExpressionofSREBP-l,Acyl-CoASynthase,Glycerol-3-PhosphateAcyltransferase,HMG-CoAReductaseandFattyAcidSynthaseinlivertissue.

Murine3T3-LIadipocytes [106]

22 Irvingia gabonensis (Aubry-LecomteexO'Rorke)Baill.(Irvingiaceae)

Seed Inhibitsadipogenesisinadipocytes.Theeffectappearstobemediatedthroughthedownregulatedexpressionofadipogenictranscriptionfactors(PPAR-γ)andadipocyte-specificproteins(leptin),andbyupregulatedexpressionofadiponectin.

Murine3T3-LIadipocytes [199]

23 Morus australis Poir.(Moraceae)

Root Increaseslipolyticeffectssuchasdecreasedintracellulartriglycerideandthereleaseofglycerol.

3T3-L1adipocytes [200]

24 Nelumbo nucifera Gaertn.(Nelumbnaceae)

Seedepicarp,leaves,seed,petals

Theextractseffectiveininhibitingpreadipocytedifferentiation.Theflavonoidsinhibitseffectonbothadipocytedifferentiationandpancreaticlipaseactivity,accumulationanddecreasesexpressionPPARγ,GLUT4,andleptininculturedhumanadipocytes,indicatingthatitinhibitsthedifferentiationofpre-adipocytesintoadipocytes.

3T3-L1(adipocyte),NIH3T3(mousefibroblast, embryo),L-02(normalhepatocyte)cellsCHO-K1,andU2OScells,

[124-127]

25 Nepeta tenuifolia Benth.(Lamiaceae)

Wholeplant Inhibitstriglycerideaccumulationin3T3-L1adipocytes,suggestinganti-obesityactivity.

3T3-L1cells [201]

26 Pericarpium zanthoxyli(Rutaceae)

Seed Decreasesexpressionoftheadipogenesis-relatedtranscriptionfactor,PPAR-γandPPAR-γ-targetgenes,suchasadipocyteprotein2(aP2),fattyacidsynthase(FAS)andotheradipocytemarkersandalsodecreaseslevelsofCCAAT/enhancer-bindingproteinβ(C/EBPβ)inadose-dependentmanner.

OP9cells [202]

27 Petasites japonicus (Siebold&Zucc.)

Flowerbuds Theextractsattenuatethreeadipogenetictranscriptionfactors,peroxisomePPAR-γ2,CCAAT/enhancer-bindingproteinandsterolregulatoryelement-bindingprotein1c.

3T3-L1murinepreadipocytes

[136]

28 Peucedanum japonicum Thunb.(Apiaceae)

Leaves PteryxindownregulatesgenesSREBP-1c,fattyacidsynthase,andacetyl-coenzymeAcarboxylase-1intreated3T3-L1adipocytesandHepG2hepatocytesandup-regulateslipidcatabolizinggenes.Inaotherstudyitwasprovedthattheextractdown-regulatesakeylipogenicactivator,SREBP1candadipocytesizemarkergene,paternallyexpressedgene1/mesoderm-specifictranscript(PEG1/MEST)inadiposetissueinvivo.

Both3T3-L1andHepG2celllines,3T3-L1andHepG2cells

[203,204]

29 Rubus chingii var. suavissimus(S.K.Lee)L.T.Lu(Rosaceae).

Leaves Theextractincreasesadipogenesisandincreasesexpressionofadiponectinandleptin.Intheearlyphaseofadipogenesis,extractincreasesthemRNAexpressionofadipogenictranscriptionfactorsCCAAT/enhancerbindingproteinαandPPAR-γ.


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30 Salicornia herbacea L.(Amaranthaceae)

Wholeplant Isorhamnetin3-О-β-D-glucopyranosidesuppressesadipogenicdifferentiationbydownregulationofperoxisomeproliferator-activatedreceptor-γ,CCAAT/enhancer-bindingproteins,SREBP1,andtheadipocyte-specificproteins.Specificmechanismmediatingtheeffectsofisorhamnetin3-О-β-D-glucopyranosideconfirmedbyactivationofAMPK.


31 Siegesbeckia pubescensL.(Amaranthaceae)

Wholeplant Theanti-obesityeffectismodulatedbycytidine-cytidine-adenosine-adenosine-thymidine/enhancerbindingproteins,andperoxisomeproliferator-activatedreceptor,geneandproteinexpressions.


32 Smilax china L.(Smilacaceae)

Leaves Polyphenolandflavonoid,exhibitsα-glucosidaseandlipidaccumulationinhibitionproperties.

3T3-L1adipocytes [208]

33 Tetrapanax papyriferus (Hook.)K.Koch(Araliaceae)

Wholeplant Theanti-obesityeffectismodulatedbycytidine-cytidine-adenosine-adenosine-thymidine/enhancerbindingproteins,andperoxisomeproliferator-activatedreceptor,geneandproteinexpressions.


34 Veratrum nigrum L.(Melanthiaceae)

Wholeplant Itdecreaseslipidaccumulationandtheexpressionsoftwomajoradipogenesisfactors,PPARandC/EBP,in3T3-L1cells.

3T3-L1cells [134]

35 Vitis labrusca L.(Vitaceae)

Seed TheextractofV. labruscainhibitslipidaccumulationofC3H10T1/2and3T3-L1cellsinadose-dependentmanner.InhibitionisassociatedwithreducedexpressionofPPAR-γ.

C3H10T1/2and3T3-L1cells

[177]

36 Vitis vinifera L.(Vitaceae)

Seedflours,peel,roots,fruit


3T3-L1preadipocytes,highfatdiet-inducedmice,murine3T3-LIadipocytes,

[54,171-178]

37 Ziziphus jujube Mill.(Rhamnaceae)

Fruit Suppresseslipidaccumulationandglycerol-3-phosphatedehydrogenase.Elicitsthemostinhibitoryeffectwithattenuationoftheexpressionofkeyadipogenictranscriptionfactors,includingPPAR-γandCCAATenhancerbindingproteins(C/EBPs)attheproteinlevel.

3T3-L1preadiocytes [209-211]

38 Germinatedbrownrice,germinatedwaxybrownrice,germinatedblackrice,andgerminatedwaxyblackrice

Seed Extractoftheseseedsdecreasesbodyweightgainandlipidaccumulationintheliverandepididymaladiposetissue.ThemRNAlevelsofadipogenictranscriptionalfactors,suchasCCAATenhancerbindingprotein(C/EBP)-α,SREBP(SREBP)-1c,andperoxisomeproliferatoractivatedreceptors(PPAR)-γ,andrelatedgenes(aP2,FAS)aredecreasedbytheseed extract.

3T3-L1murineadipocytes [212]

Table 3 Listofplantsexhibitinganti-obesityactivitystudiedonhumanvolunteers.1 Carum carvi L.

(Apiaceae)Seed Reducesweight,bodymassindex,bodyfatpercentage,

andwaist-to-hipratio.Humanclinicaltrials [213]

2 Cissus quadrangularis L.(Vitaceae)

Cylarisaformulacontains a C. quadrangularextract

Phytosterolsandfiberextractshaveanti-lipase,andanorexiantpropertiesthatreducetheabsorptionofdietaryfatsandenhancesatiationbyincreasingserumserotoninlevels.

Humanclinicaltrials [214]

3 Citrus aurantium L.(Rutaceae)

Fruits,leaves Theactiveconstituentp-synephrineincreasesmetabolicrate,energyexpenditureandincreaseinweightloss.Theleafextractdown-regulatestheexpressionofC/EBPβandsubsequentlyinhibitstheactivationofPPARγandC/EBPα.Theanti-adipogenicactivityofismediatedbytheinhibitionofAktactivationandGSK3βphosphorylation,whichinducesthedown-regulationoflipidaccumulationandlipidmetabolizinggenes,ultimatelyinhibitingadipocytedifferentiation.

Humanclinicaltrials [22,187,188]

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wasanincreaseinmetabolicrateandenergyexpenditure.Itwasalsoreportedthattheclinicaltrialsperformedonhumansfortheplant extracts [151,165,226] showed an excess fat elimination,body mass index, fat percentage and blood glucose loweringeffects. In another clinical trial study [148] the fenugreek seed

extractdecreasedthefatconsumptionandalso insulin/glucoseratio.Theessentialoilfromtheplants[124,227]suppressedfataccumulation, intracellular triglyceride and decrease in bodyweight. Ginseng which is a popular Chinese herbal medicinesignificantly decreased the weight gain and improved glucose

4 Garcinia cowa Roxb.ex Choisy(Clusiaceae)

Fruit,commerciallyavailabletablet

InhibitstheenzymeATP-dependentcitratelyase,whichcatalyzesthecleavageofcitratetooxaloacetateandacetyl-CoA.SerumapoA1levelsareincreasedbytheplantandtheserumtotalcholesterollevels.

Humanclinicaltrials [86,87]

5 Gynostemma pentaphyllum (Thunb.)Makino(Cucurbitaceae)

Leaves ActivationofAMPKby5-aminoimidazole-4-carboxamide-1-b-D-ribofuranoside(AICAR)inhibitsadipogenesisbydownregulatingPPARcandCEBP1aaswellaslipogenicfactorsincludingfattyacidbindingprotein4andlipoproteinlipase.AMPKactivationdirectlyinactivatesACCthroughSer79phosphorylation,leadingtodecreasedfatsynthesisbyreducingtheproductionofmalonyl-CoAfromacetyl-CoA.


6 Nigella sativa L.(Ranunculaceae)

CommercialNigella sativaoilpreparedbysteamdistillation.

N. sativareducestotalcholesterol,lowdensitylipoprotein(LDL)andfastingbloodglucose.Theoiliseffectiveasanadd-ontherapyinpatientswithmetabolicsyndrome.

HumanVolunteer [216,217]

7 Salacia reticulata wight(Celastraceae)

Root Significantweightandbody-fatreductionwasobservedin S. reticulata treatedanimalsandalsoBMIreductionis seen.


8 Trigonella foenum-graecum L.(Leguminosae)

Seed Dailyfatconsumption,expressedastheratiofatreportedenergyintake/totalenergyexpenditure(fat-REI/TEE),isdecreasedinoverweightsubjectsadministeredthefenugreekseedextract.Significantdecreaseintheinsulin/glucoseratioinsubjectstreatedwithfenugreekseedextract.

Clinicaltrials [219]

9 Turnera diffusaWilld.exSchult.(Passifloraceae)

Leaves Theherbalpreparationcapsulesdelaysgastricemptying,reducingthetimetoperceivedgastricfullnessandinducesweightloss.

Healthyvolunteers [220,221]

10 Vernonia amygdalina Delile(Compositae)

Leaf Fatelimination usuallyoccurredwithin2sec,2minofextractintake.ThebloodglucoselowerseffectsofV. amygdalinaleafextractwereusuallyexertedin2sec,2minofextractintakebythepatient.

Clinicaltrials [222]

11 Ziziphus jujube Mill.(Rhamnaceae)

Fruit Theextractsuppresseslipidaccumulationandglycerol-3-phosphatedehydrogenase.Z. jujubaextractelicitsthemostinhibitoryeffectwithattenuationoftheexpressionofkeyadipogenictranscriptionfactors,includingPPAR-γandCCAATenhancerbindingproteins(C/EBPs)attheproteinlevel.

Humanclinicaltrials [209-211]

Table 4. Anti-obesityeffectofplantswithmechanismofactionstudiedonisolatedcellorganelles. 1 Verbesina persicifolia

DC(Compositae)

Aerialparts 4β-cinnamoyloxy,1β,3α-dihydroxyeudesm-7,8-eneistheactiveconstituentpresent in V. persicifoliainducesbioenergeticcollapseinratlivermitochondria,demonstratingtypicaluncouplingagent.ItactsasamilduncouplerdropingΔψandincreasesrespiratorystate4.Theenergycollapse,milduncoupling,andthe fact that V. persicifoliaislargelyusedinfolkmedicines,thisplantmaybeviewedasapotentiallyeffectiveanti-obesitydrug.

Ratlivermitochondria

[223]

Table 5. Anti-obesityeffectofplantswithmechanismofactionstudiedonisolatedcellenzymes.1 Fraxinus chinensis

subsp.rhynchophylla(Hance)A.E.Murray(Oleaceae)

Stemsandbarks

Majoractivecomponentsaresecoiridoidsligstroside,oleuropein,2"-hydroxyoleuropeinandhydroxyframosideB.ThesecompoundssignificantlyinhibitpancreaticlipaseandhydroxyframosideBbeingthemostactiveinhibitorinamixedmechanismofcompetitiveandnoncompetitivemanner.

Porcinepancreaticlipase

[224]

2 Vitis vinifera L.(Vitaceae)

Seedflours,peel,roots,fruit


Purepancreaticlipase

[54,171-178]

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tolerance [115,120].P. granatum exhibits potential antiobesitymechanismincludinginhibitionofpancreaticlipaseactivityandsuppression of energy intake. Its effect on energy intake wassimilartosubutraminebutwithadifferentmechanism.

A study reported that Green tea possessed higher antioxidantactivitythanantiobesityactivityduetoitshighconcentrationofcatechins, includingepicatechins,ECGandEGCG. Itwasprovedthatantiobesityactivityofcatechinsresultedfromthecombinedactions of appetite reduction, greater lipolytic activity, energyexpenditureandadipocytedifferentiation.

TheactivecompoundsumbelliferoneandesculetinfromtheplantAegle marmeloshaveshownmarkedeffectbydepletingthelipidcontentintheadipocytesandbydecreasingthehyperlipidemia.Similarly,galanginacompoundfromAlpinia galangal showedasignificantdecreaseinserumlipids,liverweight,lipidperoxidationandaccumulationofhepaticTriglycerides.Decursinacompoundfrom Angelica gigas significantly improved glucose toleranceandreducedthesecretionofHFD-inducedadipocytokines.Thephytoconstituent compound sitosterol found in Boerhaavia diffusa is structurally similar tocholesterolhasbeensuggestedto reduce cholesterol by lowering the level of LDL-cholesterol.p-synephrinecompoundfromtheplantCitrus aurantiumshowedincreased metabolic rate, energy expenditure and increasein weight loss. In Nelumbo nucifera flavonoids showed mildinhibitoryeffectonbothadipocytedifferentiationandpancreatic

lipase activity.Among theflavonoids, flavoneswithout glucoseinhibited pancreatic lipase activity, whereas flavone glycosidesdidnotshowinhibition.Thepresenceofephedrineandpseudo-ephedrine in the plant Sida rhomboidea induced appetitesuppressionthatinhibitsbodyweightgain.

ConclusionNatural products identified from traditional medicinal plantshave always paved the way for development of new types oftherapeutics. Generally most of the compounds were isolatedfrom natural sources despite which orlistat a semi-syntheticderivativeof lipstatinhavebeenapprovedby theUS foodanddrug administration for the treatment of obesity. Orlistat is apotent inhibitor of pancreatic lipase (PL) which is a lipolyticenzymewhichhydrolysesdietary fats in the initial stepof lipidmetabolism. There have been many reports on other effectssuchasanti-oxidativestresseffectswhichmaybe important inthemanagementofotherdiseases like cardiovasculardiseasesand diabetes. The antiobesity drugs are generally preferredbasedonhighefficacyandeffectiveness.Theactiveexplorationof natural sources has provided new developments based onthe understanding of complex and redundant physiologicalmechanisms. Such explorationwill lead to a safe and effectivepharmacologicaltreatment.

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Review of Medicinal Plants for Anti-Obesity Activity...Review of Medicinal Plants for Anti-Obesity...

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