基于网络药理学及分子对接方法研究复方三黄酊抗菌机制

Study on antibacterial mechanism of compound sanhuang tincture based on network pharmacology and molecular docking

目的采用网络药理学及分子对接的研究方法对复方三黄酊抗菌活性的作用机制进行研究。方法运用大数据背景下的TCMSP数据库对复方三黄酊的化学成分和靶点进行预测。应用GeneCards数据库对相关的靶点基因进行一定程度的挑选,应用Cytoscape3.7.1软件形成一个由复方三黄酊药物、成分、靶点组成的完整的网络体系,同时应用String数据平台对存在的蛋白质进行相互作用的网络构建,应用Omicshare数据库分析GO和KEGG的作用通路。应用MOE分子对接软件将核心靶点与化合物进行分子对接,应用Discovery Studio分子建模软件将结果可视化。结果复方三黄酊发挥抗菌作用的主要潜在成分包括槲皮素、丁香油酚、β-谷甾醇、药根碱、汉黄芩素等,其作用的核心靶点为AKT1、IL6、TP53、VEGFA、TNF等35个。复方三黄酊通过关键靶点激活MAPK信号通路、磷脂酰肌醇3激酶—蛋白激酶B信号通路、IL-17信号通路、肿瘤坏死因子信号通路等。核心靶点(AKT1、IL6、TP53、VEGFA、TNF)与化合物(槲皮素、丁香油酚、β-谷甾醇、药根碱)具有较好的亲和性。结论复方三黄酊通过干预细胞增殖分化、调控炎症反应、调节免疫等发挥抗菌作用,具有多成分、多靶点、多通路的作用特征,为进一步基础研究及临床应用复方三黄酊提供了新的理论线索和研究思路。

Objective To study the action mode and mechanism of compound sanhuang tincture on antibacterial activity by means of network pharmacology.Methods TCMSP database under the background of big data was used to predict the chemical composition and target of compound sanhuang tincture.GeneCards database was used to select related gene targets to a certain extent.Cytoscape3.7.1 software was used to form compound sanhuang tincture into a complete network system composed of drugs,components and targets.Meanwhile,String data platform was used to construct the interaction network of existing proteins.Omicshare database was used to analyze the pathways of GO and KEGG action.Molecular docking software(MOE)was used to conduct molecular docking between core targets and compounds,and the molecular modeling software(Discovery Studio)was used to visualize the results.Results The main potential antibacterial components of compound sanhuang tincture included quercetin,eugenol,β-sitosterol,jatrorrizine,and wogonin,etc.There were 35 core targets such as AKT1,IL6,TP53,VEGFA and TNF.MAPK signaling pathway,PI3K-Akt signaling pathway,IL-17 signaling pathway and TNF signaling pathway were activated by compound sanhuang tincture through key targets.The core targets(AKT1,IL6,TP53,VEGFA,and TNF)showed good affinity with compounds(quercetin,eugenol,β-sitosterol,and jatrorrizine)by molecular docking.Conclusion Compound sanhuang tincture plays an antibacterial role by interfering with cell proliferation and differentiation,regulating inflammatory response and regulating immunity.It has the characteristics of multi-component,multi-target and multi-pathway.This study provides new theoretical clues and research ideas for further basic research and clinical application of compound sanhuang tincture.