基于网络药理学和分子对接技术探讨升麻治疗皮肌炎及多发性肌炎的作用机制

Study on the mechanism of Rhizoma Cimicifugae for dermatomyositis and polymyositis based on network pharmacology and molecular docking technology

目的 利用网络药理学和分子对接技术探讨升麻对皮肌炎及多发性肌炎潜在的作用机制。方法 利用中药系统药理学数据库与分析平台,筛选出升麻成分及作用靶点,以“dermatomyositis”“polymyositis”为疾病关键词在Genecards和Drugbank数据库中获取疾病基因,利用Venny 2.1取交集靶点,采用CytoScape 3.7.1软件构建成分-疾病-靶点图,借助STRING数据库进行蛋白质相互作用网络构建,并用R软件进行分析,对作用靶点进行基因本体(gene ontology,GO)分析和京都基因及基因组的百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析;使用Autoduck和Pymol软件进行分子对接及可视化展示。结果 筛选得到升麻有效成分9个,靶点60个,疾病靶点1 247个,交集靶点13个,GO富集生物过程68条,细胞组成11条、分子功能23条,KEGG富集通路61条(P <0.05)。分子对接结果提示,4个活性成分与核心靶点有较好结合能力。结论 升麻中升麻酸、脱氧升麻烃和豆甾醇等活性成分可能作用于白介素-6、肿瘤坏死因子、前列腺素内过氧化物合成酶2及过氧化物酶体增殖物激活受体γ等靶点,通过白介素-17、toll样受体以及维甲酸诱导基因Ⅰ等通路调控炎症和免疫反应。

Objective To explore the potential mechanism of Rhizoma Cimicifugae on dermatomyositis and polymyositis by using network pharmacology and molecular docking technology.Methods The components and action targets of Rhizoma Cimicifugae were screened out by using the systematic pharmacology database and analysis platform of traditional Chinese medicine system.The disease genes were obtained from Genecards and Drugbank databases with "dermatomyositis" and "polymyositis" as disease keywords.Venny 2.1 was used to obtain the intersection targets,Cytoscape 3.7.1 software was used to construct the component-disease-target map,and the STRING database was used to construct protein-protein interaction network.R software was used for analysis,Gene ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the acting targets.Autoduck and Pymol software were used for molecular docking and visual display.Results Nine active components,60 targets,1 247 disease targets,13 intersection targets,68 biological processes enriched by GO,11 cell compositions,23 molecular functions,and 61 KEGG enrichment pathways were obtained(P<0.05).The results of molecular docking indicated that the four active ingredients had good binding ability to the core target.Conclusion The active components of cimicic acid,deoxycimicidal hydrocarbon and stigmasterol may act on interleukin-6,tumor necrosis factor,prostaglandin endoperoxidase 2 and peroxisome proliferator activated receptors γ.It regulates the inflammation and immune response of myositis through interleukin-17,toll like receptor and retinoic acid-induced gene Ⅰ.