目的:利用网络药理学方法及分子对接技术探析脉管复康片治疗动脉粥样硬化(atheroscle-rosis,AS)的机制.方法:通过传统中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选脉管复康片(丹参、鸡血藤、没药、乳香、郁金)活性成分和靶基因.使用人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、药物靶标数据库(therapeutic target da-tabase,TTD)、遗传药理学与药物基因组学数据库(pharmacogenetics and pharmacogenomics knowledge base,PharmGKB)、DrugBank疾病数据库获得AS相关基因.使用Cytoscape 3.8.2构建"成分-靶点"网络.使用STRING数据库下载蛋白-蛋白互作网络(protein-protein interactions,PPI)数据,导入 Cytoscape,使用CytoNCA插件获取核心靶基因.使用R软件进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)富集分析.对活性成分及核心基因做分子对接.结果:从脉管复康片中共筛选出157个活性成分,对应AS靶基因238个,PPI核心靶基因共20个.GO功能富集显示生物学功能主要涉及脂多糖反应、细菌来源分子反应、金属离子反应、氧化应激反应等;KEGG通路富集显示主要涉及流体剪切应力和AS、AGE-RAGE信号通路、PI3K-Akt信号通路等;分子对接结果提示槲皮素、木犀草素、柚皮素、丹参酮ⅡA、刺芒柄花素、甘草查尔酮A与4个核心蛋白JUN、MAPK1、TP53、STAT3结合稳定.结论:脉管复康片可通过槲皮素、木犀草素等活性成分作用于多种信号通路及多个基因靶点治疗AS.
Discussion on the Mechanism of the Treatment of Atherosclerosis by Maiguan Fukang Tablets Based on Network Pharmacology and Molecular Docking
Objective:To discuss the mechanism of the treatment of atherosclerosis(AS)by Maiguan Fukang tablets using network pharmacology and molecular docking.Methods:The active ingredients including Danshen(Salviae miltiorrhizae radix et rhizoma),Jixueteng(Spatholobi caulis),Moyao(Myrrha),Ruxiang(Olibanum)and Yujin(Curcumae radix),and target genes of Maiguan Fukang tablets were screened from TCMSP.AS-related genes were obtained using GeneCards,OMIM,TTD,PharmGKB and DrugBank databases.The network of"ingredient-target"was constructed using Cytoscape 3.8.2.Protein-protein interactions were downloaded using STRING database,imported into Cytoscape,the core target genes were obtained using CytoNCA.GO and KEGG of the related target genes were performed using R software.Molecular docking of active ingredients and the core genes were carried out.Results:All 157 active ingredients,238 corresponding AS target genes and 20 PPI core target genes were screened out from the tablets.Go functional enrichment showed that biological functions mainly involved lipopolysaccharide reactions,bacteria-derived molecular reaction,metal ion reactions and oxidative stress reactions.KEGG pathway enrichment displayed that fluid shear stress and AS,AGE-RAGE signaling pathway,and PI3K-Akt signaling pathway were mainly involved.The results of molecular docking suggested that quercetin,luteolin,naringenin,tanshinone IIA,formononetin,and licorice chalcone A were stable in binding with four core proteins such as JUN,MAPK1,TP53 and STAT3.Conclusion:Maiguan Fukang tablets could treat AS through the active ingredients such as quercetin and luteolin,which act on multiple signalling pathway and multiple gene targets.
atherosclerosisnetwork pharmacologymolecular dockingMaiguan Fukang tabletsmechanism study
万方数据
维普
