開(kāi)心散治療CMS抑郁模型大鼠的作用機(jī)制及活性成分TenuifolisideA基于ERK和PI3K通路介導(dǎo)的神經(jīng)保護(hù)機(jī)制研究

開(kāi)心散治療CMS抑郁模型大鼠的作用機(jī)制及活性成分TenuifolisideA基于ERK和PI3K通路介導(dǎo)的神經(jīng)保護(hù)機(jī)制研究開(kāi)心散治療CMS抑郁模型大鼠的作用機(jī)制及活性成分TenuifolisideA基于ERK和PI3K通路介導(dǎo)的神經(jīng)保護(hù)機(jī)制研究

摘要：

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

關(guān)鍵詞：開(kāi)心散；TenuifolisideA；CMS抑郁模型；ERK和PI3K通路；神經(jīng)保護(hù)

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