基于网络药理学的补阳还五汤治疗阿尔兹海默症的作用机制研究薛慧安丽凤曲岩陈巧云杨柳崔劭瑜沃佳美雪张丽宏刘斌摘要目的：運用网络药理学的研究方法，初步探讨补阳还五汤治疗阿尔兹海默症（AD）的作用机制。方法：借助中药系统药理学数据库与分析平台（TCMSP）、OMIM、DrugBank、TTD数据库检索和收集AD的相关靶点;利用TCMSP和TCM@TAIWAN数据库检索和筛选补阳还五汤组方药物的活性成分，并通过PharmMapper服务器预测化合物潜在作用靶点;通过与收集的AD靶点比对获得活性成分作用的AD靶点，并利用STRING数据库和Cytoscape软件构建和分析AD靶点的PPI网络图和“组方药物-活性成分-AD靶点”网络图;分别通过DAVID系统、KOBAS3.0数据库对AD靶点进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。结果：从补阳还五汤中筛选出92个活性成分，其中来自赤芍的芍药内酯苷、4-乙基芍药苷、4-氧-甲基-芍药苷可能是重要的多效活性成分;活性成分经靶点预测和比对后确定33个抗AD靶点，其中CASP3、MAPK14、BCHE、BACE1可能是抗AD的关键靶点。活性成分通过作用上述AD靶点调控MAPK、PI3K/AKT、Rap1、Ras等信号通路，影响蛋白水解、蛋白磷酸化、雌激素应答等生物过程，抑制Aβ的生成，降低神经元炎症反应和神经细胞凋亡，减弱胆碱酯酶活性，进而达到治疗AD的目的。结论：通过网络药理学方法研究补阳还五汤治疗AD的活性成分和作用机制，揭示了补阳还五汤在治疗AD方面具有多成分、多靶点、多途径的优点，为补阳还五汤的后期实验提供新思路。关键词补阳还五汤;阿尔兹海默症;网络药理学;活性成分;靶点;通路AbstractObjective：ToexplorethemechanismofBuyangHuanwuDecoctioninthetreatmentofAlzheimer′sDisease（AD）withthemethodofnetworkpharmacology.Methods：WeretrievedandcollectedADtargetswiththehelpofTCMSP，OMIM，DrugBankandTTDdatabases.SearchedandscreenedtheactivecompoundsinBuyangHuanwuDecoctionthroughtheTCMSPandTCM@TAIWANdatabases，andpredictedpotentialtargetsofcompoundsthroughthePharmMapperserver.ObtainedtheADtargetsthatinteractwithBuyangHuanwuDecoctionbycomparingwiththecollectedADtargets.Constructingandanalyzingtheprotein-proteininteractionnetworkoftargetsofBuyangHuanwuDecoctionagainstADandthenetworkof“herbs-activecompounds-ADtargets”withSTRINGdatabaseandCytoscapesoftwareseparately.GOfunctionalannotationandKEGGpathwayenrichmentanalysiswereperformedonADtargetsthroughDAVIDsystemandKOBAS3.0database.Results：Atotalof92activecompoundswerescreenedfromBuyangHuanwuDecoction，amongwhichpaeoniflorin，4-ethylpaeoniflorinand4-O-methyl-paeoniflorinfromtheRadixPaeoniaeRubramaybetheimportantmultipleactivityingredients.Aftertargetspredictionandcomparison，33ADtargetsweredetermined，amongwhichCASP3，MAPK14，BCHEandBACE1maybethekeytargetsofBuyangHuanwuDecoctionagainstAD.TheADtargetswereaffectedbyactivecomponentstoregulateproteolysis，proteinphosphorylation，estrogenresponseandotherbiologicalprocesses，toinhibittheproductionofAβ，decreaseneuronalinflammationandapoptosisofnervecells，andreducetheactivityofcholinesterasebyparticipatinginMAPK，PI3K/AKT，Rap1，Rasandothersignalingpathways，toachievethepurposeoftreatingAD.Conclusion：ResearchontheactiveingredientsandmechanismofBuyangHuanwuDecoctioninthetreatmentofADthroughnetworkpharmacologymethods，revealingthatBuyangHuanwuDecoctionhastheadvantagesofmultiplecomponents，multipletargetsandmultiplepathwaysinthetreatmentofAD，whichprovidesanewideaforthelaterexperimentofBuyangHuanwuDecoction.KeywordsBuyangHuanwuDecoction;Alzheimer′sdisease;Networkpharmacology;Activecomponents;Targets;Pathway：R285：Adoi：10.3969/j.issn.1673-7202.2021.11.009阿尔兹海默病（AlzheimerDis...