基于网络药理和分子对接探究黄芩-黄连治疗溃疡性结肠炎的潜在作用机制

The potential action mechanism of Huangqin-Huanglian on ulcerative colitis based on network pharmacology and molecular docking

目的:基于网络药理学方法探索芍药汤君药黄芩、黄连调控肠道菌群治疗溃疡性结肠炎的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)收集黄芩、黄连的主要活性成分及对应靶点,使用Swiss Target Prediction数据库预测靶点。通过GeneCards、在线人类孟德尔遗传数据库(OMIM)、治疗靶点数据库(TTD)获取溃疡性结肠炎及肠道菌群相关靶点基因。采用Venny 2.1.0获得黄芩-黄连、溃疡性结肠炎和肠道菌群的交叉靶点。使用Cytoscape 3.9.1构建“成分-靶点”网络,筛选核心成分。使用STRING数据库、Cytoscape 3.9.1构建靶点蛋白质-蛋白质相互作用网络图,获取核心靶点。使用DAVID数据库进行富集分析。通过分子对接进一步验证其作用机制。结果:获取48个活性成分及56个交集靶点,黄芩、黄连防治溃疡性结肠炎的主要活性成分可能为汉黄芩素、槲皮素、黄连碱、表小檗碱、穆坪马兜铃酰胺等,核心靶点为肿瘤蛋白p53(Tumor Protein p53,TP53)、肿瘤坏死因子(Tumor necrosis factor,TNF)、白细胞介素(Interleukin,IL)-6、JUN原癌基因(Jun ProtoOncogene,JUN)、雌激素受体1(Estrogen Receptor 1,ESR1)。富集分析显示作用机制与癌症通路、TNF信号通路、IL-17信号通路等有关。分子对接结果显示核心成分与靶点结合良好。结论:黄芩-黄连可能通过多成分、多靶点、多通路调控肠道菌群发挥治疗溃疡性结肠炎的作用。

Objective:Based on the network pharmacology method,the action mechanism of Huangqin(Radix Scutellariae)-Huanglian(Rhizoma Coptidis),the sovereign medicines of the Shaoyao decoction(芍药汤),in the prevention and treatment of ulcerative colitis by regulating intestinal flora was explored.Methods:The main active components and corresponding targets of Huangqin and Huanglian were collected from the TCMSP database,and the targets were predicted by the Swiss Target Prediction database.Ulcerative colitis and intestinal flora-related target genes were obtained from GeneCards,OMIM,and TTD databases.Venny 2.1.0 was used to obtain the intersection targets of Huangqin-Huanglian,ulcerative colitis and intestinal flora.Cytoscape 3.9.1 was used to construct a component-target network to screen core components.The STRING database and Cytoscape 3.9.1 were used to construct the target protein-protein interaction network diagram to obtain the core targets.The enrichment analysis was carried out by DAVID database,and the action mechanism was further verified by molecular docking.Results:A total of 48 active ingredients and 56 intersecting targets were obtained,the main active ingredients of Huangqin-Huanglian in the prevention and treatment of ulcerative colitis might be baicalein,quercetin,berberine,epiberberine,Muping aristolochimid,etc..The core targets were tumor protein p53,tumor necrosis factor,interleukin-6,Jun proto-oncogene,and estrogen receptor 1.The enrichment analysis showed that the action mechanism was related to pathway in cancer,tumor necrosis factor signaling pathway,interleukin-17 signaling pathway,etc.The molecular docking results showed that the core components were well bound with the core targets.Conclusion:Huangqin-Huanglian may play a role in the prevention and treatment of ulcerative colitis through multi-component,multi-target and multi-pathway by regulating intestinal flora.