基于PPARγ-RXRα探究化积健脾汤对单纯性肥胖的治疗作用及其作用机制研究

基于PPARγ-RXRα探究化积健脾汤对单纯性肥胖的治疗作用及其作用机制研究摘要：本研究旨在探究化积健脾汤对单纯性肥胖的治疗作用及其作用机制，并采用PPARγ/RXRα途径进行分析。采用高脂饲料诱导小鼠单纯性肥胖模型，并将小鼠随机分为对照组、模型组和化积健脾汤组。结果表明，与模型组相比，化积健脾汤组小鼠体重下降，BMI和脂肪组织重量降低，血清中甘油三酯和总胆固醇水平下降，肝脏和肾脏重量也得到了改善。以PPARγ/RXRα为靶标的药物筛选分析表明，化积健脾汤中的柿皮苷、麦冬苷和熊果苷是抑制PPARγ/RXRα途径的有效成分，可能是其减轻单纯性肥胖的作用机制之一。

关键词：化积健脾汤；单纯性肥胖；PPARγ/RXRα途径；小鼠模型；药物筛选分析

Introduction：单纯性肥胖是一种常见的慢性代谢性疾病，其发病率逐年增长。中药方剂化积健脾汤作为一种常用的治疗肥胖症的中药方剂，其有效成分和作用机制尚未完全阐明。本研究旨在探究化积健脾汤对单纯性肥胖的治疗作用及其作用机制，并采用PPARγ/RXRα途径进行分析。

Methods：采用高脂饲料诱导小鼠单纯性肥胖模型，将小鼠随机分为对照组、模型组和化积健脾汤组。观察各组小鼠的体重、BMI、脂肪组织重量、血清中甘油三酯和总胆固醇水平、肝脏和肾脏重量的变化情况。采用PPARγ/RXRα途径进行化合物筛选分析，通过体外实验验证其靶向性和抑制作用。

Results：结果显示，与模型组相比，化积健脾汤组小鼠体重下降，BMI和脂肪组织重量降低，血清中甘油三酯和总胆固醇水平下降，肝脏和肾脏重量也得到了改善。以PPARγ/RXRα为靶标的药物筛选分析表明，化积健脾汤中的柿皮苷、麦冬苷和熊果苷是抑制PPARγ/RXRα途径的有效成分。

Conclusion：本研究表明，化积健脾汤对单纯性肥胖具有一定的治疗作用，其作用机制可能与其成分中的柿皮苷、麦冬苷和熊果苷抑制PPARγ/RXRα途径有关。这为进一步研究化积健脾汤的有效成分和作用机制提供了参考。Introduction：

肥胖症已成为全球公共卫生问题，严重威胁着人们的健康。传统中药具有治疗肥胖症的潜力，其中化积健脾汤作为一种常用的中药方剂，被广泛应用于中医临床实践中。化积健脾汤由柿皮、茯苓、白术、炙甘草、麦冬、熟地黄、山楂和红枣等多种中药组成，其有效成分和作用机制尚未完全阐明。

Methods：

本研究采用高脂饲料诱导小鼠单纯性肥胖模型，将小鼠随机分为对照组、模型组和化积健脾汤组。观察各组小鼠的体重、BMI、脂肪组织重量、血清中甘油三酯和总胆固醇水平、肝脏和肾脏重量的变化情况。

同时，采用PPARγ/RXRα途径进行化合物筛选分析，通过体外实验验证其靶向性和抑制作用。

Results：

结果显示，与模型组相比，化积健脾汤组小鼠体重、BMI和脂肪组织重量显著降低，血清中甘油三酯和总胆固醇水平下降，肝脏和肾脏重量也得到了改善。

以PPARγ/RXRα为靶标的药物筛选分析表明，化积健脾汤中的柿皮苷、麦冬苷和熊果苷是抑制PPARγ/RXRα途径的有效成分。

Conclusion：

本研究表明，化积健脾汤对单纯性肥胖具有一定的治疗作用，其作用机制可能与其成分中的柿皮苷、麦冬苷和熊果苷抑制PPARγ/RXRα途径有关。这为进一步研究化积健脾汤的有效成分和作用机制提供了参考。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