目的 通过网络药理学预测白藜芦醇(resveratrol,RSV)治疗阿尔茨海默症(Alzheimer's disease,AD)的关键靶点.方法 利用TCMSP数据库检索含RSV的中药,并对其性味、归经和功效进行归纳分析.利用SwissTargetPrediction、SEA、HERB数据库预测RSV作用靶点;利用GeneCards、OMIM、TTD、DisGeNRT数据库检索AD靶点;取RSV的作用靶点与AD靶点的交集为潜在治疗靶点.利用DAVID数据库进行潜在治疗靶点的GO分析.利用STRING数据库获取潜在治疗靶点的KEGG富集分析和蛋白质交互作用(protein-protein interaction,PPI),并用Cytoscape绘制PPI网络图.AlzData数据库验证AD关键靶点变化.SwissDock网站对RSV与关键蛋白进行分子对接.结果 含RSV中药的性味为苦味最多;归经中入肝经最多;功效中清热解毒功效最多.RSV预测靶点388个,AD靶点1624个,交集靶点119个.KEGG富集通路中的阿尔兹海默症通路共富集到 27 个蛋白.AlzData数据库分析发现AD患者表达发生变化的蛋白.分子对接结果发现,RSV与丝氨酸/苏氨酸激酶(serine/threonine kinase 1,AKT1)、白介素-6(interleukin-6,IL-6)、连环蛋白-1(β-catenin,CTNNB1)、肿瘤坏死因子(tumor necrosis factor,TNF)均有较好的结合能力.结论 网络药理分析结果显示RSV对AD的治疗是多靶点、多通路的,可为后续研究方向提供参考.
Objective Key targets of resveratrol(RSV)in the treatment of Alzheimer's disease(AD)are predicted by network pharmacology.Methods The traditional Chinese medicines which contain RSV were searched by the TCMSP database,and their property and flavor,meridian distribution and phamacologic action were summarized and analyzed.The targets of RSV were predicted by SwissTargetPrediction,SEA and HERB databases.The targets of AD were retrieved using GeneCards,OMIM,TTD and DisGeNRT databases.The intersection targets of RSV and AD were taken as the potential therapeutic targets.Analysis gene ontology(GO)annotations of potential therapeutic targets by biological information annotation database(DAVID).Did KEGG cluster analysis and protein interactions(PPIs)of potential therapeutic targets in STRING database,and mapped PPI networks in Cytoscape.Verified changes of AD key targets in AlzData database.Docking RSV and key proteins in SwissDock website.Results The most Tropism of taste of the traditional Chinese medicines that contain RSV:bitter,cold,in the liver.And the main phamacologic action is clearing away heat and toxic materials.There are 388 predicted targets of RSV,1624 targets of AD,119 intersection targets.Alzheimer's pathway in KEGG enriched pathway was enriched to 27 proteins.The proteins which expression changed of AD patients was analysised in AlzData database.The results of molecular docking showed that RSV had good binding ability with AKT1,IL-6,CTNNB1 and TNF.Conclusion The results of network pharmacological analysis show that the treatment of AD by RSV is multi-target and multi-pathway,which can provide reference for subsequent research directions.