菟絲子擬雌激素作用的體內(nèi)直接作用物質(zhì)及代謝組學研究

菟絲子擬雌激素作用的體內(nèi)直接作用物質(zhì)及代謝組學研究摘要：

菟絲子作為一種傳統(tǒng)草藥，具有廣泛的醫(yī)療作用。同時，菟絲子中的化學成分也引起了人們的強烈興趣。本研究旨在探究菟絲子擬雌激素作用的體內(nèi)直接作用物質(zhì)及代謝組學方面的研究。研究采用擬雌激素三倍體(ST-60)小鼠為實驗對象，通過LC-MS/MS和生物信息學方法分析了小鼠血液、肝組織及尿液中的代謝物，并對代謝通路進行分析和驗證，以期找到與菟絲子擬雌激素作用相關的生物標記物。結果表明，菟絲子內(nèi)的皂甙類化合物、維生素類化合物、甾體激素以及多種酚類化合物都具有一定的擬雌激素作用，直接作用物質(zhì)主要為葫蘆巴素、金絲桃苷、山萘酚等。代謝組學結果表明，葫蘆巴素代謝為廢物代謝，金絲桃苷代謝為腸道菌代謝和主要代謝物生成兩種途徑，而山萘酚則主要為肝臟代謝。最后，通過體內(nèi)實驗和體外細胞實驗驗證了菟絲子擬雌激素作用的體內(nèi)直接作用物質(zhì)和代謝途徑。本研究結果可為菟絲子的藥理研究、功效提取以及臨床開發(fā)提供一定的參考。

關鍵詞：菟絲子；代謝組學；擬雌激素；直接作用物質(zhì)；生物標記物

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