基于网络药理学和分子对接探究白芍-麦冬药对治疗干燥综合征的作用机制

Study on the Action Mechanism of Paeoniae-Ophiopogon in the Treatment of Sicca Syndrome Based on Network Pharmacology and Molecular Docking

目的运用网络药理学和分子对接探究白芍-麦冬药对治疗干燥综合征(sjogren syndrome,SS)的作用机制。方法通过BATMAN、Gene Cards、OMIM、Drug Bank、TTD、DISGENET数据库和Cytoscape软件发现并探究相关治疗靶点作用关系。通过String数据库构建蛋白质-蛋白质相互作用网络图。通过DAVID平台进行GO与KEGG富集分析。使用AutoDock Tools1.5.7软件进行分子对接。结果白芍-麦冬有57个有效活性成分,362个作用靶点,SS有1219个疾病相关靶点。主要有效成分为豆甾醇、没食子酸、β-谷甾醇,核心靶点AKT1、IL1B、CAT、IGF1。GO分析中,GO生物过程(biological process,BP)主要包括基因表达的负调控、脂多糖的反应、RNA聚合酶II启动子转录的正向调节等;GO细胞组分(cellular components,CC)主要包括细胞表面、细胞外区域、细胞外体等;GO分子功能(molecular function,MF)主要包括血红素结合、类固醇结合、RNA聚合酶II转录因子活性等。KEGG富集分析中主要包括MAPK信号通路、TNF信号通路、cAMP信号传导途径等;分子对接实验表明其主要活性成分与核心靶点之间存在良好的结合活性。结论白芍-麦冬药对通过多靶点、多通路发挥治疗SS的作用。

Objective:To study the action mechanism of paeoniae-ophiopogon in the treatment of sicca syndrome(SS)by network pharmacology and molecular docking.Methods:The relationship between relevant therapeutic targets was discovered and explored through BATMAN,Gene Cards,OMIM,Drug Bank,TTD,DISGENET database and Cytoscape software.The network diagram of protein-protein interaction was constructed by String database.GO and KEGG enrichment analysis was performed by using the DAVID platform.Molecular docking was performed by AutoDock Tools1.5.7 software.Results:There were 57 active ingredients and 362 active targets in Paeoniae-Ophiopogon,and 1219 disease-related targets in SS. The main active ingredients were stigmasterol,gallic acid,β-sitosterol,and the core targets were AKT1,IL1B,CAT,IGF1.In GO analysis,biological processes(BP)of GO mainly included negative regulation of gene expression,lipopolysaccharide reaction,and positive regulation of RNA polymerase II promoter transcription.GO cellular components(CC)mainly include cell surface,extracellular region,extracellular body,etc.The molecular function(MF)of GO mainly included heme binding,steroid binding and RNA polymerase II transcription factor activity.The KEGG enrichment analysis mainly included MAPK signaling pathway,TNF signaling pathway,cAMP signaling pathway,etc.The molecular docking experiments showed that there was good binding activity between the main active components and the core targets.Conclusion:Paeoniae-Ophiopogon can play a role in the treatment of SS through multi-target and multi-pathway.