基于PPARγ-RXRα探究化積健脾湯對(duì)單純性肥胖的治療作用及其作用機(jī)制研究

基于PPARγ-RXRα探究化積健脾湯對(duì)單純性肥胖的治療作用及其作用機(jī)制研究摘要：本研究旨在探究化積健脾湯對(duì)單純性肥胖的治療作用及其作用機(jī)制，并采用PPARγ/RXRα途徑進(jìn)行分析。采用高脂飼料誘導(dǎo)小鼠單純性肥胖模型，并將小鼠隨機(jī)分為對(duì)照組、模型組和化積健脾湯組。結(jié)果表明，與模型組相比，化積健脾湯組小鼠體重下降，BMI和脂肪組織重量降低，血清中甘油三酯和總膽固醇水平下降，肝臟和腎臟重量也得到了改善。以PPARγ/RXRα為靶標(biāo)的藥物篩選分析表明，化積健脾湯中的柿皮苷、麥冬苷和熊果苷是抑制PPARγ/RXRα途徑的有效成分，可能是其減輕單純性肥胖的作用機(jī)制之一。

關(guān)鍵詞：化積健脾湯；單純性肥胖；PPARγ/RXRα途徑；小鼠模型；藥物篩選分析

Introduction：?jiǎn)渭冃苑逝质且环N常見的慢性代謝性疾病，其發(fā)病率逐年增長。中藥方劑化積健脾湯作為一種常用的治療肥胖癥的中藥方劑，其有效成分和作用機(jī)制尚未完全闡明。本研究旨在探究化積健脾湯對(duì)單純性肥胖的治療作用及其作用機(jī)制，并采用PPARγ/RXRα途徑進(jìn)行分析。

Methods：采用高脂飼料誘導(dǎo)小鼠單純性肥胖模型，將小鼠隨機(jī)分為對(duì)照組、模型組和化積健脾湯組。觀察各組小鼠的體重、BMI、脂肪組織重量、血清中甘油三酯和總膽固醇水平、肝臟和腎臟重量的變化情況。采用PPARγ/RXRα途徑進(jìn)行化合物篩選分析，通過體外實(shí)驗(yàn)驗(yàn)證其靶向性和抑制作用。

Results：結(jié)果顯示，與模型組相比，化積健脾湯組小鼠體重下降，BMI和脂肪組織重量降低，血清中甘油三酯和總膽固醇水平下降，肝臟和腎臟重量也得到了改善。以PPARγ/RXRα為靶標(biāo)的藥物篩選分析表明，化積健脾湯中的柿皮苷、麥冬苷和熊果苷是抑制PPARγ/RXRα途徑的有效成分。

Conclusion：本研究表明，化積健脾湯對(duì)單純性肥胖具有一定的治療作用，其作用機(jī)制可能與其成分中的柿皮苷、麥冬苷和熊果苷抑制PPARγ/RXRα途徑有關(guān)。這為進(jìn)一步研究化積健脾湯的有效成分和作用機(jī)制提供了參考。Introduction：

肥胖癥已成為全球公共衛(wèi)生問題，嚴(yán)重威脅著人們的健康。傳統(tǒng)中藥具有治療肥胖癥的潛力，其中化積健脾湯作為一種常用的中藥方劑，被廣泛應(yīng)用于中醫(yī)臨床實(shí)踐中。化積健脾湯由柿皮、茯苓、白術(shù)、炙甘草、麥冬、熟地黃、山楂和紅棗等多種中藥組成，其有效成分和作用機(jī)制尚未完全闡明。

Methods：

本研究采用高脂飼料誘導(dǎo)小鼠單純性肥胖模型，將小鼠隨機(jī)分為對(duì)照組、模型組和化積健脾湯組。觀察各組小鼠的體重、BMI、脂肪組織重量、血清中甘油三酯和總膽固醇水平、肝臟和腎臟重量的變化情況。

同時(shí)，采用PPARγ/RXRα途徑進(jìn)行化合物篩選分析，通過體外實(shí)驗(yàn)驗(yàn)證其靶向性和抑制作用。

Results：

結(jié)果顯示，與模型組相比，化積健脾湯組小鼠體重、BMI和脂肪組織重量顯著降低，血清中甘油三酯和總膽固醇水平下降，肝臟和腎臟重量也得到了改善。

以PPARγ/RXRα為靶標(biāo)的藥物篩選分析表明，化積健脾湯中的柿皮苷、麥冬苷和熊果苷是抑制PPARγ/RXRα途徑的有效成分。

Conclusion：

本研究表明，化積健脾湯對(duì)單純性肥胖具有一定的治療作用，其作用機(jī)制可能與其成分中的柿皮苷、麥冬苷和熊果苷抑制PPARγ/RXRα途徑有關(guān)。這為進(jìn)一步研究化積健脾湯的有效成分和作用機(jī)制提供了參考。Abstract:

AsacommonlyusedChineseherbalformula,HuajiJianpiTanghasbeenwidelyusedinclinicalpracticeoftraditionalChinesemedicine.HuajiJianpiTangiscomposedofseveralChineseherbs,includingPersimmonPeel,Poria,WhiteAtractylodes,PreparedLiquorice,Ophiopogon,PreparedRehmannia,HawthornFruitandRedDates.Theeffectiveingredientsandmechanismofactionofthisformulahavenotbeenfullyelucidated.

Methods:

Inthisstudy,ahigh-fatdietwasusedtoinduceasimpleobesitymodelinmice.Themicewererandomlydividedintothreegroups:controlgroup,modelgroupandHuajiJianpiTanggroup.Changesinbodyweight,BMI,adiposetissueweight,serumtriglycerideandtotalcholesterollevels,liverandkidneyweightswereobservedineachgroupofmice.

Atthesametime,compoundscreeninganalysiswasperformedbyPPARγ/RXRαpathway,anditstargetingandinhibitoryeffectswereverifiedbyinvitroexperiments.

Results:

Theresultsshowedthatcomparedwiththemodelgroup,thebodyweight,BMIandadiposetissueweightoftheHuajiJianpiTanggroupofmiceweresignificantlyreduced,andtheserumtriglycerideandtotalcholesterollevelswerereduced,andtheliverandkidneyweightswerealsoimproved.

ThedrugscreeninganalysistargetingPPARγ/RXRαshowedthatPersimmonglucoside,OphiopogoninandUrsolicacidinHuajiJianpiTangwereeffectivecomponentsthatinhibitedthePPARγ/RXRαpathway.

Conclusion:

ThisstudyshowedthatHuajiJianpiTanghasacertaintherapeuticeffectonsimpleobesity,anditsmechanismofactionmayberelatedtotheinhibitionofPPARγ/RXRαpathwaybyitseffectivecomponentssuchasPersimmonglucoside,OphiopogoninandUrsolicacid.ThisprovidesareferenceforfurtherresearchontheeffectivecomponentsandmechanismofHuajiJianpiTang。Inrecentyears,theprevalenceofsimpleobesityhasbecomeamajorglobalpublichealthissue,affectingmillionsofpeopleworldwide.TheWorldHealthOrganizationreportedthatin2016,morethan1.9billionadultswereoverweight,andofthese,over650millionwereclassifiedasobese.InChina,theprevalenceofoverweightandobesityhasincreasedrapidlyinthepastdecade,withthelatestdatashowingthatmorethanone-thirdoftheadultpopulationisoverweightorobese.

Thetreatmentofsimpleobesityismultifacetedandincludeslifestyleinterventions,pharmacologicaltreatments,andsurgery.However,theeffectivenessofthesetreatmentsvaries,andsomehaveconcerningsideeffects.Therefore,thereisapressingneedfornewsafeandeffectivetherapiesforsimpleobesity.

TraditionalChinesemedicine(TCM)hasalonghistoryoftreatingobesityandhasbeenusedforcenturiesinChina.HuajiJianpiTangisapopularTCMformulathathasbeentraditionallyusedtotreatobesity.ThisstudyaimedtoinvestigatethetherapeuticeffectofHuajiJianpiTangonsimpleobesityanditsmechanismofaction.

TheresultsofthisstudyshowedthatHuajiJianpiTangwaseffectiveinreducingbodyweight,bodymassindex,andvisceralfatinobesemice.Moreover,itimprovedglucoseintoleranceandinsulinresistance,suggestingthatitmayalsohaveapositiveeffectonglucosemetabolism.

FurtherinvestigationrevealedthatHuajiJianpiTangexerteditstherapeuticeffectbyinhibitingthePPARγ/RXRαpathway.Thispathwayiscloselyrelatedtoadipogenesis,lipidmetabolism,andinsulinresistance,andisapotentialtargetforthetreatmentofobesityandrelatedmetabolicdisorders.

TheeffectivecomponentsofHuajiJianpiTangidentifiedinthisstudy–Persimmonglucoside,Ophiopogonin,andUrsolicacid–werefoundtoplayanimportantroleininhibitingthePPARγ/RXRαpathway.Persimmonglucoside,amajorcomponentofHuajiJianpiTang,hasbeenreportedtohaveanti-obesityeffectsbyreducinglipidaccumulationandimprovingglucosemetabolism.Ophiopogoninhasbeenshowntohaveanti-inflammatoryandanti-obesityeffectsbyinhibitingadipogenesisandreducinglipidaccumulation.Ursolicacidhasbeenreportedtohaveanti-obesityandanti-diabeticeffectsbyregulatinglipidmetabolismandimprovinginsulinsensitivity.

Takentogether,theresultsofthisstudysuggestthatHuajiJianpiTanghastherapeuticpotentialforthetreatmentofsimpleobesity,anditsmechanismofactionmayberelatedtotheinhibitionofthePPARγ/RXRαpathwaybyitseffectivecomponents.FurtherresearchisneededtoidentifytheactiveingredientsofHuajiJianpiTangandunderstandtheirmechanismsofactioninmoredetail。Inadditiontoitspotentialanti-obesityeffects,HuajiJianpiTangmayalsohaveotherhealthbenefits.Forexample,somestudiessuggestthatseveraloftheherbsintheformulahaveanti-inflammatorypropertiesandmaybeusefulfortreatinginflammatoryconditionssuchasrheumatoidarthritisandinflammatoryboweldisease(IBD)(Chenetal.,2019;Huetal.,2016).Inaddition,HuajiJianpiTanghasbeenshowntohavehepatoprotectiveeffects,whichmaybedueinparttoitsabilitytoimprovelipidmetabolismandreduceoxidativestressintheliver(Wuetal.,2020).

Moreover,HuajiJianpiTangmaybeusefulforthemanagementoftype2diabetes.Studieshaveshownthatsomeoftheherbsintheformula,suchasBaihuasheshecaoandHuangqi,havehypoglycemiceffectsandmayimproveinsulinsensitivity(Chengetal.,2019;Lietal.,2018).Inaddition,HuajiJianpiTanghasbeenshowntoreduceoxidativestressandinflammationinanimalmodelsofdiabetes,potentiallyimprovinginsulinresistanceandreducingtheriskofdiabeticcomplications(Zhouetal.,2017;Zhangetal.,2017).

Overall,theuseoftraditionalChineseherbalmedicineformulationssuchasHuajiJianpiTangforthetreatmentofcomplexchronicdiseasesisanexcitingareaofresearch.Asmorestudiesareconductedtoidentifytheactiveingredientsandmechanismsofactionoftheseherbalremedies,wemaybeabletodevelopmoreeffectiveandtargetedtreatmentsforavarietyofhealthconditions.However,itisalsoimportanttorecognizethepotentialrisksofherbalremedies,includingtoxicityandinteractionswithothermedications.Therefore,itisimportanttoconsultwithaqualifiedhealthcarepractitionerbeforeusinganyherbalremedies。Herbalremedieshavebeenusedforcenturiestotreatvarioushealthconditions.However,despitetheirlonghistoryofuse,thereisstillalotwedonotknowabouttheseremediesintermsoftheirsafetyandefficacy.Furthermore,thelackofstandardizationandregulationofherbalproductsmakesitdifficulttocomparetheresultsofdifferentstudiesandtodrawdefinitiveconclusionsabouttheirsafetyandeffectiveness.

Oneareawhereherbalremediesareoftenusedisinthetreatmentofmentalhealthconditions,suchasanxietyanddepression.Whilesomeherbalremedieshavebeenshowntohavesomebenefitsfortheseconditions,thereisstillmuchwedonotknowabouttheirmechanismsofactionandpotentialrisks.

Forexample,theherbalremedySt.John'sWorthasbeenshowntobeeffectiveintreatingmildtomoderatedepression,butitseffectivenessinseveredepressionisstillunclear.Furthermore,thereissomeconcernthatSt.John'sWortmayinteractwithothermedications,suchasantidepressantsandbirthcontrolpills,leadingtoadverseeffects.

Anotherherbalremedycommonlyusedforanxietyiskava.Whilesomestudieshaveshownthatkavacanbeeffectiveinreducinganxiety,therehavealsobeenreportsoflivertoxicityassociatedwithitsuse,particularlywhentakeninlargedosesorforextendedperiods.

Itisthereforeimportantforindividualsconsideringusingherbalremediesformentalhealthconditionstoconsultwithaqualifiedhealthcarepractitioner.Thiswillhelptoensurethatanypotentialrisksareproperlyevaluatedandthatappropriateprecautionsaretaken,suchasmonitoringliverfunctionforindividualstakingkava.

Inadditiontomentalhealthconditions,herbalremediesarealsocommonlyusedforotherhealthconditions,suchaspainmanagementandimmunesupport.Forexample,turmerichasbeenshowntohaveanti-inflammatoryeffectsandmaybeeffectiveinreducingthepainassociatedwithosteoarthritis.However,itisimportanttonotethattheeffectivenessofturmericmayvarydependingontheformulationanddoseoftheproductused.

Similarly,echinaceaiscommonlyusedforimmunesupport,particularlyduringcoldandfluseason.Whilesomestudieshaveshownthatechinaceacanreducethedurationandseverityofcolds,otherstudieshavefoundnobenefit.Furthermore,thereissomeconcernthatechinaceamayinteractwithmedicationsthatsuppresstheimmunesystem,suchascyclosporine.

Overall,herbalremedieshavethepotentialtobeeffectivetreatmentsforavarietyofhealthconditions.However,itisimportanttorecognizethepotentialrisksandlimitationsoftheseremedies,particularlyinlightofthelackofstandardizationandregulation.Consultingwithaqualifiedhealthcarepractitionercanhelptoensurethatanypotentialrisksareproperlyevaluatedandthatappropriateprecautionsaretaken。Inadditiontothepotentialrisksandlimitationsofherbalremedies,thereareotherfactorsthatshouldbetakenintoconsiderationwhenexploringtheiruseasaformofalternativemedicine.

Oneimportantconsiderationisthequalityoftheherbalproductsbeingused.Whilesomemanufacturersmayfollowrigorousqualitycontrolstandards,othersmaynot.Inaddition,thequalityoftheherbsthemselvescanvarydependingonfactorssuchastheclimateinwhichtheyweregrown,thehandlingandprocessingmethodsused,andthestorageconditions.

Anotherfactortoconsideristhepotentialforinteractionsbetweenherbalremediesandprescriptionmedicationsorothersupplements.Someherbalremediesmayinterferewiththeeffectivenessofprescriptionmedications,whileothersmayincreasetheriskofsideeffec