Rev. bras. farmacogn. vol.26 número2

w ww.e l s e v i e r . c o m / l o c a t e / b j p

Original

article

Determination

of

the

regulatory

properties

of

Yucca

schidigera

extracts

on

the

biochemical

parameters

and

plasma

hormone

levels

associated

with

obesity

Ismail

Kucukkurt

,

Esra

Küpeli

Akkol

,

Funda

Karabag

,

Sinan

Ince

,

Ipek

Süntar

,

Abdullah

Eryavuz

_,

_Nalan

_Bays¸

_u

_Sözbilir

a_{AfyonKocatepeUniversity,FacultyofVeterinaryMedicine,DepartmentofBiochemistry,Afyonkarahisar,Turkey} b_{GaziUniversity,FacultyofPharmacy,DepartmentofPharmacognosy,Etiler,Ankara,Turkey}

c_{UsakUniversity,FacultyofArtScience,DepartmentofMolecularBiologyandGenetic,Us¸ak,Turkey}

d_{AfyonKocatepeUniversity,FacultyofVeterinaryMedicine,DepartmentofPharmacologyandToxicology,Afyonkarahisar,Turkey} e_{AfyonKocatepeUniversity,FacultyofVeterinaryMedicine,DepartmentofPhysiology,Afyonkarahisar,Turkey}

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received11September2015 Accepted6December2015 Availableonline29January2016

Keywords:

Adiponectin Ghrelin Insulin Leptin Obesity Mice

a

b

s

t

r

a

c

t

YuccaschidigeraOrtgies,Asparagaceae,isaherbaceousplant.Duetothehighsaponincontentthe powderedbranchesandleavesareusedasnaturalfoodadditiveforhumanandanimal.Theaimofthis studywastoinvestigatetheeffectsofY.schidigeraextractsonplasmaleptin,ghrelin,adiponectin,insulin, thyroidhormonesandsomebiochemicalparametersinmicefedahigh-fatdiet.MaleSwissAlbinomice weredividedintosevenequalgroups.GroupI(negativecontrolgroup)wasgivenstandarddiet;Group IIwasgivenhigh-fatdiet;GroupIIIwasgivenhigh-fatdietwithcarboxymethylcellulose;GroupsIV–VII weregivenhexane,petroleumether,ethylacetate,andmethanolextractsofY.schidigeraand high-fatdietviagastricgavagefor60days.High-fatdietsignificantlyincreasedplasmaleptin,insulin,free T3hormone,glucose,cholesterol,low-densitylipoprotein,triacylglyceride,aspartateaminotransferase andalanineaminotransferaselevels,andsignificantlydecreasedplasmaghrelin,adiponectinandfree T4hormonelevels.Ontheotherhand,hormonelevels,lipidprofileandbiochemicalparameterswere improvedbytheadministrationofthePEextract.Y.schidigeraextractscouldbeusedaspreventive medicineinnutritionaldisordersviaregulatingenergymetabolismandhormonalfunctions.

©2016SociedadeBrasileiradeFarmacognosia.PublishedbyElsevierEditoraLtda.Allrightsreserved.

Introduction

YuccaschidigeraOrtgiesisaherbaceousplantfromthefamily

Asparagaceae,nativetothedesertsofthesouth-westernUnited StatesandnorthernMexico.Duetotheantiprotozoaland antifun-galpropertiesandhormone-stimulatingeffects ithasbeenused safelytoenhanceperformance asfeedmaterialfor livestockas wellas foodmaterial for humans(Narutoshi,1992).Moreover, inrecentresearches,Y.schidigerahasshowntopossess antiox-idant, anti-hypercholesterolemic, anticarcinogenic, antiarthritic, anti-inflammatory,antiprotozoal,antifungalandantihypertensive properties.Theplantwasshown tohavesecondarymetabolites suchas eugenol,caffeicacid, rosmarinicacidand␣-tocopherol. Moreover,thedried andpowderedplantmaterial alsocontains approximately10%steroidalsaponinsandisusedcommerciallyas

∗ Correspondingauthor.

E-mail:[email protected](I.Kucukkurt).

asaponinsource(Francisetal.,2002;Piacenteetal.,2004;Enginar

etal.,2006;KucukkurtandDündar,2013).

Saponinsareaclassofsecondarymetabolitesfoundinseveral plantspecies.Morespecifically,theyproducesoap-likefoaming whenshakeninaqueoussolutions,and,intermsofstructure,one ormorehydrophilicglycosidemoietiescombinedwithalipophilic triterpene or steroidal aglycone.These compounds are used in phytotherapy and in the cosmetic industry for their cytotoxic, hemolytic,molluscicidal,anti-inflammatory,antifungal,antiyeast, antibacterialandantiviralactivities(Leungetal.,1997;Senetal.,

1998; Bachran et al., 2006) as well as in the pharmaceutical

industryforthesemi-synthesisofsteroidaldrugs(Chwaleketal., 2006).Moreover,saponinsstimulateluteinizinghormonerelease leading to abortifacient properties (Francis et al., 2002), have immunomodulatory potential (Sunet al., 2009), cytostatic and cytotoxiceffects(Bachranetal.,2008)andadjuvantpropertiesfor vaccines(Sjolanderetal.,1998).Duetotheirphysiological proper-ties,saponinsarenowexpectedtoserveasfunctionalcomponents infood.Theyhavebeenreportedtodecreaseplasmacholesterol

http://dx.doi.org/10.1016/j.bjp.2015.12.005

in rats when added to theirdiets (Oakenfull, 1981; Sidhu and

Oakenfull,1986).

Fattydiet,aswellasimbalancebetweenthefoodintakeand energy expenditure are the factors affecting the prevalence of obesity(Altunkaynak,2005;Milagroetal.,2006).Obesityand over-weightposeamajorriskforseriousdiet-relatedchronicdiseases, includingtype-IIdiabetes,cardiovasculardiseases,hypertension, strokeandcertainformsofcancer.Leptin,insulinandT3areamong

themostimportanthormonestoprovidethisbalance(Otukonyong etal.,2005).Leptin,anadiposetissuehormone,regulatesbodyfat massandbodyweightbydecreasingtheappetiteandincreasing energyexpenditure(Zabrockaetal.,2006).

Thepresentstudywasplannedtodeterminetheeffectsofthe extractsobtainedfromY.schidigera,whichwasreportedtoberich insaponinsinthepreviousstudies,onleptin,ghrelin,insulinand thyroidhormonesandsomebiochemicalparametersinmicefeda high-fatdiet.

Materialsandmethods

Plantmaterial

Yucca schidigera Ortgies, Asparagaceae, standard powder

(Sarsaponin30® _{contains more than 8%steroidal saponin)was}

purchasedfromDesertKingInternational(SanDiego,CA,USA).

Preparationoftheextracts

Y.schidigerapowder(500g) wassuccessivelyextracted with

5lofhexane (HE),petroleumether (PE),ethylacetate(EA) and methanol(ME)bypercolationmethodatroomtemperature.After completionofextractiontheextractswerefilteredandthesolvent wasremovedbydistillationunderreducedpressureandlow tem-perature(40–50◦_{C)onarotaryevaporatortogivecrudeextracts.}

Extractswereweighedandyieldpercentageswerecalculatedas 17.93%forHE,26.42%forPE,11.02%forEAand9.27%forME.

Animals

Male SwissAlbino mice (25–35g) were purchased fromthe animalbreedinglaboratoriesofAfyonKocatepeUniversity Experi-mentalAnimalResearchandApplicationCenter(Afyon,Turkey). The animalswere allowedtoacclimatize tothe animal facility foratleast7daybeforeexperimentstarted.Theroomconditions weremaintainedina12hlight/12hdarkcycleatroom tempera-ture(25±3◦C),withrodentstandarddietandwaterprovidedad

libitum.Aminimumoftenanimalswasusedineachgroup.The studywaspermittedbytheInstitutionalAnimalEthicsCommittee (AnkaraUniversityEthicalCouncilStudyNumber:2009/34)and wasperformedaccordingtotheinternationalrulesconsideringthe animalexperimentsandbiodiversityright.

Experimentalprotocol

Twodifferentcontrolgroupswereemployedinthestudy.The negativecontrolgroupwasmaintainedonstandardpelletdietand wateradlibitumwithoutadministeringanyplantextract(negative controlgroup).Thehigh-fatdiet(HFD)groupreceivedspecialdiet containing40%beef tallowforeightweeks(HFDgroup-positive control).Thevehiclecontrolgroupreceived0.5%CMCsuspension indistilledwater andwasmaintainedonHFD(CMCgroup).On theotherhand,theexperimentalgroupanimalsreceivedhexane (HE),petroleumether(PE),ethylacetate(EA),andmethanol(ME) extractsobtainedfromY.schidigeraalongwithHFD.Extractswere administeredorallyaftersuspendingindistilled waterand0.5% sodiumcarboxymethylcellulose(CMC)byusingagastricgavageat

100mg/kgdosesdailyforeightweeks.Thisdosewasdetermined accordingtoapreviouspreliminarystudy(Avcietal.,2006).Blood samplesweretakenfromtheheartintotubeswithheparinand plasmawasobtainedattheendoftheexperimentalperiod,then centrifugationperformedat1500×g(+4◦_{C)for10minandkeptat} −30◦Cinadvanceofassays.

Biochemicalanalysis

Plasma leptin (Biovendor, Czech Republic, Cat No. RD291001200R), insulin (Millipore, USA, Cat No. EZRMI-13K), ghrelin(Millipore, USA,CatNo.EZRGRT-91K), totaladinopectin (Biovendor, Czech Republic, Cat No. RD293023100R), total tri-iodothyronine(T3)(DRGInternationalInc.,USA,CatNo.EIA-4569),

total tetra-iodothyronine (T4) (DRG InternationalInc., USA, Cat

No.EIA4568),freetri-iodothyronine(FT3)(DRGInternationalInc., USA,CatNo.EIA-2385)andfreetetra-iodothyronine(FT4)(DRG. InternationalInc.,USA,CatNo.EIA2386)weremeasuredusingan enzyme-linkedimmunosorbentassay(ELISA).

Liverdamagewasassessedbytheestimationofserumlevels ofalanineaminotransferase(ALT),andaspartateaminotransferase (AST)byusingcommercialkitsTecoDiagnosticsassaykit(Teco Diagnostics, CA,USA). Serum levels of total protein (Tp), urea, totalcholesterol(Tc),glucose,lowdensitylipoprotein-cholesterol (LDL-c),highdensitylipoprotein-cholesterol(HDL-c)and triacyl-glyceride (Tg) were determined using COBAS test kits (Roche Diagnostics Systems, Istanbul, Turkey) according tothe manu-facturers’ instructions in Laboratoryof Biochemistry,Faculty of VeterinaryMedicine,UniversityofAfyonKocatepe(Turkey).

Statisticalanalysisofdata

Thedataobtainedfromtheanimalexperimentswasexpressed as mean and standard error (±SEM). Thestatistical differences among the experimental groups were evaluated by one-way ANOVAandDuncanposthoctestsusingtheSPSScomputer soft-wareprogram. A differenceof p<0.05 in themean values was consideredsignificant.

Results

BodyweightsofthemiceareshowninTable1.Supplementation ofHFDtotheanimalsduringeightweekssignificantlyincreased thebodyweightcomparedtothecontrolgroup(p<0.05).Onthe otherhand,duringtheexperimentalperiodPEextractprevented theweightgainofmicecomparedtotheothergroups.

Plasmaglucose,TC,LDL,HDL,TG,AST,andALPwerefoundtobe highinHFDandCMC+HFDgroupscomparedtothecontrolgroup (p<0.05)asshowninTable2.Ontheotherhand,administration of100mg/kgY.schidigeraextracts,especiallyHEandPE,decreased thelevelsoftheseparameters(p<0.05).Theseresultssuggestthat

Y.schidigeraextracts havecapacity toalleviatethebiochemical

statuscausedbyHFD.

Supplementation of HFD increased leptin, insulin, and FT3 whereasdecreasedghrelin,adiponectin,andFT4(p<0.05).In addi-tion,TT4andTT3levelswerenotchangedinallgroups(Table3).On theotherhand,administrationof100mg/kgY.schidigeraextracts especiallyPEresultedinreversalofHFD-inducedhormonelevels (p<0.05).TheseresultssuggestthatY.schidigeraextractsaffected hormonestatus.

Discussion

Table1

TheeffectsofYuccashidigeraextractsonbodyweightinmice(n:15;mean±SEM).

Groups 0day 15day 30day 45day 60day pvalue

Control 25.43±0.75 25.57±0.67 25.17±0.69 25.61±0.87 26.00±0.99 0.966

HFD 26.44±0.79c _29.44±1.02b _32.27±1.20b _35.40±1.06a _36.90±1.18a _0.000

HFD+CMC 26.19±0.82c _29.61±1.21b _31.86±1.28b _36.16±0.93a _36.63±1.21a _0.000

HEextract 25.86±1.06b _30.85±0.98a _29.47±1.44a _30.01±1.10a _30.08±0.98a _0.038

PEextract 26.93±1.36 30.31±1.77 30.20±0.89 30.81±0.88 30.68±1.04 0.083

EAextract 27.87±1.49b _31.60±1.42a _31.76±1.26a _33.86±1.08a _34.19±1.08a _0.012

MEextract 26.17±0.87b 33.31±0.74a 33.27±0.77a 33.90±0.72a 34.64±0.72a 0.000

a,b,c_{ValueswithdifferentletterswithinacolumnaresignificantlydifferentbyDuncan’smultiplerangetest.}

HE,hexane;PE,petroleumether;EA,ethylacetate;ME,methanol.

Table2

TheeffectsofYuccaschidigeraextractsonbloodbiochemicalparametersinmice(n:15;mean±SEM).

Groups Glucose(mg/dl) Tc(mg/dl) LDL-c(mg/dl) HDL-c(mg/dl) Tg(mg/dl) Tp(g/dl) AST(U/L) ALT(U/L)

Control 103.6±2.50cd _88.71±2.69c _22.30±2.59c _85.66±2.45c _64.37±3.16bc _{4.30±0.08 39.34±4.09}b _164.1±11.3b HFD 163.7±9.28a* _189.1±8.45a* _66.7±6.47a* _116.8±2.71b* _99.85±4.25a* _{4.34±0.15 76.19±4.48}a* _235.5±23.8a*

HFD+CMC 179.5±7.47a 197.6±14.31a 70.6±3.13a 118.2±4.37b 102.9±5.14a 4.37±0.12 71.68±5.02a 241.7±20.1a

HEextract 91.03±3.01d _137.7±8.65b _49.32±1.99b _139.1±6.09a _76.00±4.55b _{4.83±0.12 36.28±2.93}b _173.1±13.1b

PEextract 118.2±7.35c _129.3±5.29b _42.97±1.48b _111.3±3.96b _66.71±3.74bc _{4.77±0.12 46.26±2.42}b _179.3±12.1b

EAextract 124.1±7.17c _128.2±3.06b _62.64±4.94a _108.6±3.61b _57.01±5.01c _{4.50±0.18 36.80±2.97}b _173.9±14.6b

MEextract 148.4±13.2b _148.5±6.81b _65.0±3.97a _124.4±9.03b _66.43±6.82bc _{4.31±0.23 44.09±2.99}b _180.1±10.8b

pvalue 0.000 0.000 0.000 0.000 0.000 0.067 0.000 0.003

* _{HFDgroupisstatisticallydifferentcomparedtothecontrolgroup(p<0.05)}

a,b,c_{ValueswithdifferentletterswithinacolumnaresignificantlydifferentbyDuncan’smultiplerangetest(p<0.05).}

HE,hexane;PE,petroleumether;EA,ethylacetate;ME,methanol.

micegivenfatexhibitedweightgainasinthelongtermstudies carriedoutwithHFD(Chaetal.,2000).Comparedtothecontrol group,theincreasein15daysliveweightwasfoundtobe statisti-callysignificantinallgroupsbutthePEandHEgroups.Theother measurementswerealsosupportedthesedata.

Althoughbody fatindexandbodymassindexarethemajor determinants of leptin levels, insulin, glucocorticoids and pro-lactinstimulateleptinsynthesiswhileNPL,thyroidhormones,GH, somatostatin,freefattyacidsandlongexposuretocoldinhibitit

(Kucukkurt,2015).Inapreviousstudyby˙Is¸bilenetal.(2007)HFD

fedratsduringfiveweeks,theplasma,aortandliverleptinlevels increased.Similarly,inourstudy,plasmaleptinlevelsincreasedin thehigh-fatdietandCMCgroups.InY.schidigeraextractgroups, however,leptinlevelsdecreasedsignificantlyalthoughmicewere fedahigh-fatdiet.Thedecreaseofleptinlevelsintheextractgroups andincreaseinhigh-fatdietgroupswereparallelwiththechanges inthelive-weightasshowninTable1.Indeed,Kimetal.(2005)

fedtheratswithhigh-fatdietforeight weeksandthenrefined thesteroidalsaponinsinRedKoreanGinseng,whichisconsidered asasteroidalsaponinsourcelikeY.schidigera,andadministered itintraperitoneallyforthree weeksat adoseof200mg/kg/day. Attheend ofthestudy, itwasnoted that plasmaleptinlevels decreasedsignificantly in theanimalsthat weregiven saponin,

andtheresearcherssuggestedthatthiscouldbeduetothefact thatsaponinresultedindecreaseinlive-weightandbodyfatmass. Inanother studybythesameresearchers,protopanaxadiol and protopanaxatriol-typesaponinsfromRedGinsengwere adminis-teredtotheratsfedaHFDat50mg/kg/daydose.Itwasreportedthat thedecreaseinplasmaleptinlevelscouldbeattributedto thermo-genesispropertiesofthesaponins(Kimetal.,2009).Thementioned researchesontheactivityofthesaponinsontheleptinlevels, sup-portedourresultswhichrevealadecreaseinbodyfatmassinmice withtheadministrationofY.schidigeraextracts.

Consistentwiththesefindings,inourstudy,bothghrelinand adinopectinlevelsdecreasedsignificantlyinthemicefedaHFD compared tothe control group.Ghrelin levelsincreased inthe PEandHEgroupswhiletheydidnotchangeintheotherextract groups.ThisincreaseinthePEandHEgroupsisconsistentwith thedecreaseinleptinlevelsandlive-weight.Intheotherextract groups,nochangewasseeninghrelinhormonelevelscompared totheHFDgroupandinthesegroupslive-weightdecreasewas notsimilartothatinthePEandHEgroups.Inourstudy,insulin hormoneincreasedstatistically,particularlyintheHFDandCMC groups.Increaseininsulinreflectsthatbloodglucosewasstored asglycogenin theliverand asfattyacidsin theadipose tissue

(Bays¸uSözbilirandBays¸u,2008).Increaseinadiposetissuealso

Table3

TheeffectsofYuccaschidigeraextractsonsomehormonesinmice(n:15;mean±SEM).

Groups Leptin(ng/ml) Ghrelin(mg/dl) Adiponectin(mg/dl) Insulin(ng/ml) TT4(␮g/dl) ST4(ng/ml) TT3(␮g/dl) ST3(pg/ml)

Control 28.14±1.75b _1.21±0.05a _1.41±0.13a _0.44±0.05c _{34.45±3.45 0.36±0.04}a _{18.33±0.15 1.91±0.05}b

HFD 57.41±4.13a* _0.79±0.06b* _0.79±0.09b* _2.07±0.24a* _{41.39±1.22 0.14±0.02}b* _{18.58±0.14 3.52±0.33}a*

HFD+CMC 54.24±4.81a _0.73±0.04b _0.81±0.11b _2.21±0.15a _{42.44±2.47 0.15±0.02}b _{18.90±0.26 3.03±0.31}a

HEextract 36.55±2.04b _0.81±0.04b _1.49±0.12a _0.56±0.11bc _{36.89±1.53 0.42±0.04}a _{18.41±0.04 3.25±0.17}a

PEextract 36.05±3.13b 1.38±0.07a 1.52±0.08a 0.80±0.04bc 43.54±2.57 0.49±0.05a 18.44±0.03 3.26±0.09a

EAextract 37.81±5.72b _0.77±0.07b _1.21±0.11a _0.84±0.04b _{43.70±3.37 0.50±0.04}a _{18.47±0.09 3.16±0.18}a

MEextract 35.39±2.27b _0.75±0.09b _1.46±0.10a _0.79±0.12bc _{40.02±2.88 0.44±0.07}a _{18.45±0.05 3.19±0.07}a

pvalue 0.000 0.000 0.000 0.000 0.126 0.000 0.098 0.000

* _{HFDgroupisstatisticallydifferentcomparedtothecontrolgroup(p<0.05).}

a,b,c_{ValueswithdifferentletterswithinacolumnaresignificantlydifferentbyDuncan’smultiplerangetest(p<0.05).}

increasesleptinhormonelevelsintheblood(Pateletal.,1998).

Srinivasanetal.(2005)reportedthatbodyweightincreasesinrats

fedaHFD,whichleadstoincreaseinplasmaglucose, triacylglyc-eride,totalcholesterolandinsulinlevelscomparedtothecontrol group.Besides,WinzellandAhren(2004)studiedtheeffectofHFD andreportedthatinsulinlevelsincreaseinmiceparallelto feed-ingonaHFD.Inthepresentstudy,thesamesituationwasseenin theHFDgroup,however,insulinlevelsdecreasedintheY. schidig-eraextractadministered-groupssuggestingthatactiveingredients foundinextractsmayprobablyplayaroleinthisaction.Areview byMargeticetal.revealedthatmanystudiesconductedinhumans andratssuggestthathyperinsulinemicconditionsincreaseplasma leptinlevels.Pateletal.(1998)reportedthatplasmaleptin lev-elsdecreaseindiabeticrats,butadministrationofinsulinactsby increasingplasmaleptinlevels.Our findingsarefoundtobein accordwiththosepreviousdata.

Consideringthyroidhormonemeasurements,althoughinour studytherewasnotanydifferencebetweenthetotalT4andT3and

freeT3levelsincreased,freeT4hormonedecreasedintheY.

schidi-geraextractgroupscomparedtotheHFDandCMCgroupsandwe didnotnoteanychangecomparedtocontrolgroup.Ourprevious studyshowsthatescinwhichcontainssaponineffectsserumT3

andT4levelsinHFDfedmice(Avcietal.,2010).Althoughwedid

notspotanystudyinliteraturethatfocusespeciallyonsaponins andthyroidhormones,therearedatasuggestingthatshort-and long-termuseofnaturalandsyntheticflavanoidscausedecreasein plasmaT3andT4levels(VanderHeidietal.,2003).Fainetal.(1997)

foundthatadministrationofT3tohypothyroidratsdecreased

lep-tinmRNAlevelsby40%atthe8thhour;therefore,theysuggested highthyroidhormonelevelscandiminishleptinlevels.Zabrocka

etal.(2006)showedthatserumleptinlevelsandwhiteadipose

tissuemRNAlevelsthatareconsideredasindicatorsofleptin syn-thesisdecreaseinrats,towhichtheyhadgivenvariousamountsof T3.Insomestudies,however,nocorrelationwasreportedbetween

thyroidhormonesandleptin(FriedmanandHalaas,1998). StudiesshowthatHFDincreasesALTandASTlevelsintheblood

(Friedmanet al.,1996).Inthis study,it wasalsoobservedthat

plasmaASTandALTlevelsincreasedandthisincreasewaslessin theY.schidigeraplantextractgroups.TheplantY.schidigera con-tainsmainlysteroidalsaponinsaswellasvegetalchemicalssuch asphenolic substances, fiber, resveratroland stilbens in itsdry matterandthesesaponinsarewidelyusedinindustryand stock-breeding(KucukkurtandDündar,2013).Itwasshowedinseveral studiesthatplantscontainingsaponinactbyreducingthe absorp-tionofnutritionsinthedigestivetractandcanaltermetabolism bythisroute.Y.schidigeralowerslipidmetabolismandblood glu-coselevels.Itisthoughtthattheseeffectsofsaponinsarerevealed whentakeninsmallamountsandtheyparticularlyalternormal absorptionoflipidsandglucoseinthedigestivetract(Kucukkurt

andDündar,2013).Y.schidigeraactsonlipidmetabolismand

low-erscholesterol,LDLandtriacylglyceridelevels(Kimetal.,2003;

Kucukkurtetal.,2011).Whentheextractgroupsweretakeninto

account,thelowestvaluethatdecreasedglucoselevelsofallthe groupswastheHE-administeredgroup.Whileadecreasein choles-terolandtriacylglyceridelevelswasnotedinalltheextractgroups, LDLlevelsdecreasedonlyintheHEandPEgroups.Findingsinthis studyindicatetheeffectofY.schidigeraonlipidmetabolismand similarresultswerealsoobtainedintheotherstudies(Inceetal.,

2013;KucukkurtandDündar,2013).Here,Y.schidigeragenerated

aregulatoryeffectonthelipidprofileandlipidmetabolismby reg-ulatinghepaticfunctions.Asaconclusion,extractsobtainedfrom

Y.schidigeracanbeusedforthepreventionofthediseasescaused byHDFandregulationoftheenergymetabolismandhormonal functions.Petroleumetherandhexaneextractsexertthemost sig-nificanteffect,yet,furtherstudiesshouldbeconductedtoreveal theactivesecondarymetabolites.

Authors’contributions

IK,FKandNBScontributedtobiochemicalanalyses.EKAandIS contributedintheselectionoftheplantmaterial,preparationofthe plantextractsandwritingthemanuscript.SIandAEcontributedin theapplicationofthetestmaterialstotheanimals.Alltheauthors havereadthefinalmanuscriptandapprovedthesubmission.

Conflictsofinterest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgement

ThisstudywassupportedbyAfyonKocatepeUniversity Sci-entificResearchProjectsCommissionwiththeProjectnumberof 09.VF.11.

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