開心散治療CMS抑郁模型大鼠的作用機制及活性成分TenuifolisideA基于ERK和PI3K通路介導的神經(jīng)保護機制研究

開心散治療CMS抑郁模型大鼠的作用機制及活性成分TenuifolisideA基于ERK和PI3K通路介導的神經(jīng)保護機制研究開心散治療CMS抑郁模型大鼠的作用機制及活性成分TenuifolisideA基于ERK和PI3K通路介導的神經(jīng)保護機制研究

摘要：

本文旨在探究中藥開心散治療慢性壓力誘導失去意識大鼠(CMS)抑郁模型的作用機制及活性成分TenuifolisideA的神經(jīng)保護機制。采用行為學和分子學方法，研究發(fā)現(xiàn)，開心散能夠減緩大鼠CMS模型引起的抑郁行為，特別是對抑郁模型大鼠的活力水平有顯著的提高作用。同時，開心散對CMS模型大鼠海馬區(qū)、前額葉皮質區(qū)ERK和PI3K通路有明顯的上調作用，進一步分析發(fā)現(xiàn)，TenuifolisideA是開心散的主要活性成分，且能夠介導ERK和PI3K通路發(fā)揮神經(jīng)保護作用。這表明，在開心散治療CMS抑郁模型大鼠過程中，TenuifolisideA通過介導ERK和PI3K通路發(fā)揮神經(jīng)保護作用，從而發(fā)揮其治療作用。

關鍵詞：開心散；TenuifolisideA；CMS抑郁模型；ERK和PI3K通路；神經(jīng)保護

Abstract:

ThepurposeofthisstudyistoexplorethemechanismofthetraditionalChinesemedicineHappyGranuleintreatingchronicstress-inducedunconsciousnessdepressionmodelrats(CMS)andtheneuroprotectivemechanismofitsactivecomponentTenuifolisideA.Thebehavioralandmolecularmethodswereused.TheresultsshowedthatHappyGranulecanalleviatethedepressivebehaviorcausedbyCMSinrats,especiallysignificantincreaseintheactivitylevelofdepressivemodelrats.Atthesametime,HappyGranulehasasignificantupregulationeffectontheERKandPI3KpathwaysinthehippocampusandprefrontalcortexofCMSmodelrats.FurtheranalysisfoundthatTenuifolisideAisthemainactivecomponentofHappyGranule,andcanmediatetheneuroprotectiveeffectofERKandPI3Kpathways.ThesefindingsindicatethatinthetreatmentofCMSdepressionmodelrats,TenuifolisideAplaysatherapeuticrolebymediatingtheneuroprotectiveeffectofERKandPI3KpathwaysinHappyGranule.

Keywords:HappyGranule;TenuifolisideA;CMSdepressionmodel;ERKandPI3Kpathways;neuroprotectionDepressionisacommonanddebilitatingpsychiatricdisorderthataffectsmillionsofpeopleworldwide.Theneurobiologicalmechanismsunderlyingdepressionarestillnotfullyunderstood.However,itisknownthatthedysfunctionofvariousneurotransmittersystems,aswellaschangesinneuroplasticityandneuroinflammation,playsignificantrolesinthedevelopmentandprogressionofdepression.Therefore,identifyingpotentialtargetsforthetreatmentofdepressioniscrucial.

OnesuchpotentialtherapeutictargetfordepressionistheERKandPI3Kpathways.Thesepathwaysareinvolvedinneuroplasticity,neuronalsurvival,andsynapticfunction,andhavebeenshowntobedysregulatedindepression.PreviousstudieshavereportedthatNTRK2,agenethatencodesforthereceptorofbrain-derivedneurotrophicfactor(BDNF),isupregulatedinthehippocampusofratsexposedtochronicunpredictablestress,whichhasbeensuggestedtobeamodelofdepression.ThisupregulationisassociatedwithincreasedactivityoftheERKpathway,whichinturnleadstoincreasedexpressionofBDNF.Similarly,ithasbeenshownthatactivationofthePI3Kpathwaypromotesneuroplasticityandimprovessymptomsinanimalmodelsofdepression.

HappyGranuleisatraditionalChinesemedicinethathasbeenusedforthetreatmentofdepressionformanyyears.PreviousstudieshaveshownthatHappyGranulecanimprovedepressivebehaviorsinratsexposedtochronicmildstress,whichisanothermodelofdepression.However,themechanismsunderlyingitstherapeuticeffectsarestillunclear.Inourstudy,weinvestigatedthepotentialneuroprotectiveroleofHappyGranuleintheCMSdepressionmodelandfoundthatTenuifolisideA,themainactivecomponentofHappyGranule,canmediatetheneuroprotectiveeffectofERKandPI3Kpathways.

OurresultssuggestthatTenuifolisideAmaybeapromisingcandidateforthetreatmentofdepression.FurtherstudiesareneededtoelucidatethemolecularmechanismsunderlyingitstherapeuticeffectsandtoevaluateitssafetyandefficacyinhumanclinicaltrialsInadditiontoitspotentialintreatingdepression,HappyGranuleanditsactiveingredientTenuifolisideAhavealsoshownpromisingresultsinotherareasofmentalhealth.

OnestudyfoundthatTenuifolisideAcanimprovecognitivefunctionandpreventmemoryimpairmentinanimalmodelsofAlzheimer'sdisease.AnotherstudydemonstratedthatHappyGranulecanalleviatesymptomsofanxietyandimprovesleepqualityinpatientswithgeneralizedanxietydisorder.

Furthermore,HappyGranulehasbeenshowntohaveanti-inflammatorypropertiesandcanmodulatetheimmunesystem.Thismayhaveimplicationsforawiderangeofconditions,fromautoimmunediseasestoviralinfections.

Overall,thefindingsonHappyGranuleandTenuifolisideAsuggestthatthesenaturalcompoundsmayholdgreatpromiseforimprovingmentalandphysicalhealth.Furtherresearchisneededtofullyunderstandtheirmechanismsofactionandpotentialapplications,buttheinitialresultsarehighlyencouragingInadditiontothebenefitsofHappyGranuleandTenuifolisideAformentalandphysicalhealth,thereisgrowinginterestinthepotentialofnaturalcompoundsforpromotinglongevityandhealthyaging.Manyresearchersbelievethatagingislargelydrivenbychronicinflammationandoxidativestress,andthattherapiesthattargettheseprocessesmaybeeffectiveinpromotinghealthyaging.

Onesuchcompoundthathasreceivedagreatdealofattentioninrecentyearsisresveratrol,anaturalcompoundfoundingrapes,redwine,andotherplants.Resveratrolhasbeenshowntohaveanti-inflammatoryandantioxidantproperties,andmayalsohelptostimulatetheproductionofmitochondria,theenergy-producingorganelleswithincells.

Studiesofresveratrolhavesuggestedthatitmayhaveawiderangeofpotentialapplications,fromimprovingcardiovascularhealthtopreventingdiabetes,cancer,andneurodegenerativediseases.Itisalsocurrentlybeinginvestigatedasapotentialtherapyforaging-relateddeclinesincognitivefunctionandphysicalperformance.

Othernaturalcompoundsthathaveshownpromiseforpromotinghealthyagingincludecurcumin,acompoundfoundinturmeric,andepigallocatechin-3-gallate(EGCG),acompoundfoundingreentea.Bothofthesecompoundshavebeenshowntohaveanti-inflammatoryandantioxidantproperties,andmayalsohelptoprotectagainstage-relatedcognitivedeclineandneurodegenerativediseases.

Overall,thereisgrowingevidencethatnaturalcompoundsmayholdgreatpromiseforimprovingmentalandphys