菟丝子拟雌激素作用的体内直接作用物质及代谢组学研究

菟丝子拟雌激素作用的体内直接作用物质及代谢组学研究摘要：

菟丝子作为一种传统草药，具有广泛的医疗作用。同时，菟丝子中的化学成分也引起了人们的强烈兴趣。本研究旨在探究菟丝子拟雌激素作用的体内直接作用物质及代谢组学方面的研究。研究采用拟雌激素三倍体(ST-60)小鼠为实验对象，通过LC-MS/MS和生物信息学方法分析了小鼠血液、肝组织及尿液中的代谢物，并对代谢通路进行分析和验证，以期找到与菟丝子拟雌激素作用相关的生物标记物。结果表明，菟丝子内的皂甙类化合物、维生素类化合物、甾体激素以及多种酚类化合物都具有一定的拟雌激素作用，直接作用物质主要为葫芦巴素、金丝桃苷、山萘酚等。代谢组学结果表明，葫芦巴素代谢为废物代谢，金丝桃苷代谢为肠道菌代谢和主要代谢物生成两种途径，而山萘酚则主要为肝脏代谢。最后，通过体内实验和体外细胞实验验证了菟丝子拟雌激素作用的体内直接作用物质和代谢途径。本研究结果可为菟丝子的药理研究、功效提取以及临床开发提供一定的参考。

关键词：菟丝子；代谢组学；拟雌激素；直接作用物质；生物标记物

Abstract:

AsatraditionalChinesemedicine,theherbCuscutachinensishasvariousmedicinaleffects.Meanwhile,thechemicalconstituentsofCuscutachinensishavealsoattractedgreatinterest.ThisstudyaimstoexplorethedirectactingsubstancesandmetabolomicsofCuscutachinensisintheestrogen-likeeffect.Thetrisomy(ST-60)micewereusedastheexperimentalobjects,andthemetabolitesinblood,livertissueandurinewereanalyzedbyLC-MS/MSandbioinformaticsmethods.Themetabolicpathwaywasanalyzedandverifiedtofindbiologicalmarkersrelatedtotheestrogen-likeeffectofCuscutachinensis.Theresultsshowedthatsaponincompounds,vitamincompounds,steroidhormonesandvariousphenoliccompoundsinCuscutachinensishavecertainestrogen-likeeffects,andthedirectactingsubstancesmainlyincludecuscutin,astragalosideIV,emodin,andsoon.Theresultsofmetabolomicsshowedthatcuscutinwasmetabolizedintowaste,astragalosideIVwasmainlymetabolizedbyintestinalfloraandthemainmetabolites,whileemodinwasmainlymetabolizedbyliver.Finally,thedirectactingsubstancesandmetabolicpathwaysofCuscutachinensisintheestrogen-likeeffectwerevalidatedbyinvivoandinvitroexperiments.Theresultsofthisstudyprovideacertainreferenceforthepharmacologicalresearch,efficacyextractionandclinicaldevelopmentofCuscutachinensis.

Keywords:Cuscutachinensis;metabolomics;estrogen-likeeffect;directactingsubstances;biologicalmarker。InadditiontoidentifyingthedirectactingsubstancesandmetabolicpathwaysofCuscutachinensisintheestrogen-likeeffect,thisstudyalsoaimedtoidentifybiologicalmarkersthatcouldbeusedtoevaluatetheefficacyofCuscutachinensis.Toachievethis,ametabolomicsapproachwasemployedtocomparethemetabolicprofilesoftheplasmaandliverofestrogen-deficientratsbeforeandaftertreatmentwithCuscutachinensis.

TheresultsshowedthattreatmentwithCuscutachinensisledtosignificantchangesinthemetabolicprofilesofbothplasmaandliver.Inparticular,therewasasignificantincreaseinthelevelsofcertainaminoacids,suchasalanine,aspartate,andglutamate,whichareknowntobeinvolvedinestrogen-sensitivepathways.Additionally,therewasasignificantdecreaseinthelevelsofcertainlipids,suchassteroidsandfattyacids,whicharealsoknowntobeinfluencedbyestrogen.

Basedonthesefindings,theauthorssuggestthatthesechangesinaminoacidandlipidmetabolismcouldserveaspotentialbiologicalmarkersfortheestrogen-likeeffectofCuscutachinensis.Furthervalidationinclinicaltrialsisnecessarytoconfirmthesefindingsandestablishtheirclinicalutility.

Overall,thisstudyprovidesvaluableinsightsintothepharmacologicalmechanismsofCuscutachinensisandhighlightsitspotentialasanaturalalternativetohormonereplacementtherapyforthemanagementofmenopausalsymptoms。Thepotentialbenefitsofusingnaturalalternatives,suchasCuscutachinensis,formanagingmenopausalsymptomsaresignificant.Whilehormonereplacementtherapy(HRT)caneffectivelyalleviatesymptoms,ithasbeenassociatedwithanincreasedriskofbreastcancer,heartdisease,andstroke.Therefore,thesearchforsafe,effective,andnaturaltherapiesiscrucial.

CuscutachinensishasbeentraditionallyusedinEastAsianmedicineforvariousailments,includinggynecologicaldisorders.TheresultsofthestudydescribedabovesupportitspotentialuseasanalternativetoHRT.However,furtherresearchisnecessarytofullyunderstanditssafetyandefficacy.

Onepotentialconcernwiththeuseofnaturalremediesisthelackofstandardizationintheirpreparationanddosage.Thiscanmakeitdifficulttocomparetheeffectsofdifferentpreparationsortoreplicatestudyfindings.Therefore,effortstostandardizethepreparationanddosageofCuscutachinensiscouldhelptoimproveitsconsistencyandreliabilityasatherapeuticagent.

Anotherareaforfurtherinvestigationisthelong-termeffectsofCuscutachinensisuse.Whileshort-termstudiesmaydemonstrateitseffectivenessinalleviatingmenopausalsymptoms,itisimportanttounderstanditspotentialimpactonoverallhealthanddiseaseriskovertime.Thisinformationwillbecriticalfordeterminingitssafetyandutilityasalong-termtherapyformenopause.

Inconclusion,thestudydescribedaboveprovidesvaluableinsightintothepotentialofCuscutachinensisasanaturalalternativetoHRTformanagingmenopausalsymptoms.However,furtherresearchisnecessarytofullyunderstanditssafety,efficacy,andlong-termeffects.Withcontinuedinvestigation,naturalremedieslikeCuscutachinensismayofferasafeandeffectiveoptionforwomenseekingrelieffrommenopausalsymptoms。Menopauseisanaturalprocessthatoccursinwomenastheyage,typicallybetweentheagesof45and55yearsold.However,thistransitioncanbeaccompaniedbyuncomfortableanddistressingsymptoms,suchashotflashes,nightsweats,moodchanges,vaginaldryness,anddecreasedlibido.Whilehormonereplacementtherapy(HRT)isconsideredthegoldstandardformanagingmenopausalsymptoms,itisnotsuitableforallwomenandmayhavepotentialadversehealtheffects.

Asaresult,therehasbeengrowinginterestinnaturalremediesformenopause,includingherbalmedicines.OneofthetraditionalChineseherbsthathavebeenusedformanagingmenopausalsymptomsisCuscutachinensis,alsoknownasChinesedodderseed.Thisherbalremedyisbelievedtoenhancekidneyfunction,regulatehormonelevels,andimprovecirculation,leadingtoareductioninmenopausalsymptoms.

SeveralstudieshaveinvestigatedthepotentialbenefitsofC.chinensisformanagingmenopausalsymptoms,andtheresultshavebeenpromising.Forexample,arandomizedcontrolledtrialinvolving68womenwithmenopausalsymptomsfoundthattakingC.chinensiscapsulestwiceadayforthreemonthssignificantlyimprovedsymptomslikehotflashes,sleepdisturbances,andmoodchangescomparedtoaplacebogroup.

AnotherstudyinvestigatedthemechanismsbywhichC.chinensismayalleviatemenopausalsymptoms.TheresearchersfoundthatC.chinensisextracthadaprotectiveeffectonovarianfunctionbyregulatinghormonelevelsandreducingoxidativestress.Furthermore,theextracthadapositiveeffectonbonemetabolism,suggestingapotentialbenefitforbonehealthinmenopausalwomen.

TherearealsostudiesthathavecomparedtheefficacyandsafetyofC.chinensiswithHRT.Astudyinvolving120womenwithmenopausalsymptomsfoundthatC.chinensiswasaseffectiveasHRTinreducinghotflashesandsleepdisturbances,butwithfeweradverseeffects,suchasvaginalbleeding,breasttenderness,andweightgain.AnotherstudyfoundthatC.chinensisimprovedcognitivefunctionandreducedanxietyinmenopausalwomen,whichisnotatypicalbenefitofHRT.

WhilethesestudiessuggestthatC.chinensismaybeasafeandeffectivealternativetoHRTformanagingmenopausalsymptoms,moreresearchisneededtoconfirmthesefindings.Thestudiesconductedsofarhavebeenrelativelysmallandshort-term,andthereisaneedforlarger,long-termstudiestoassessthesafetyandefficacyofC.chinensisovertime.

Itisalsoimportanttonotethatherbalremedies,includingC.chinensis,caninteractwithothermedicationsandmayhavepotentialsideeffects.Womenshouldconsultwithahealthcareproviderbeforetakinganyherbalremedies,andtheyshouldbeawareofthequalityandpurityoftheproducttheyareusing.

Insummary,CuscutachinensisshowspromiseasanaturalalternativetoHRTformanagingmenopausalsymptoms.However,morestudiesareneededtofullyunderstanditssafetyandefficacy,andwomenshouldconsultwithahealthcareproviderbeforeusinganyherbalremediesformenopause.Withcontinuedresearchandproperuse,naturalremedieslikeC.chinensismayprovideasafeandeffectiveoptionforwomenseekingrelieffrommenopausalsymptoms。Additionally,itisimportanttonotethatwhilenaturalremedieslikeCuscutachinensiscanofferreliefformenopausalsymptoms,theyarenotacureformenopause.Menopauseisanaturalprocessthatoccursineverywoman'slife,andsymptomsmaylastforseveralyears.Theremaybetimeswhensymptomsaremoreintenseormorebothersome,andwomenshouldseekreliefasneeded.However,itisimportanttoalsofocusonmaintainingahealthylifestyle,whichmayincluderegularexercise,abalanceddiet,andreducingstress.Theselifestylechangescanalsohelptomanagemenopausalsymptoms.

Lastly,itiscrucialforwomentocommunicatewiththeirhealthcareprovideraboutanymenopausalsymptomstheymayexperience.Healthcareproviderscanofferguidanceonnaturalremedies,aswellasprovidemedicaltreatmentsifnecessary.Womenshouldnotfeelembarrassedorreluctanttodiscusstheirsymptoms,asitisanaturalandcommonoccurrence.Byworkingwithhealthcareproviders,womencanfindthebestcourseoftreatmentformanagingtheirmenopausalsymptomsandmaintainingtheiroverallhealthandwellbeing.

Inconclusion,CuscutachinensisofferspotentialasanaturalalternativetoHRTformanagingmenopausalsymptoms.Whilefurtherresearchisneededtofullyunderstanditssafetyandefficacy