基于网络药理学和分子对接技术探讨五苓散治疗肥胖2型糖尿病的作用机制

Exploring the Mechanism of Wuling San in Treatment of Obese Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

目的:通过网络药理学和分子对接技术探讨五苓散治疗肥胖2型糖尿病(T2DM)的作用机制。方法:利用TCMSP数据库收集五苓散各药味的化学成分及对应靶点;通过OMIM、Drungbank和Denecards数据库整理肥胖T2DM的有关靶点;在Venny平台绘制成分-疾病靶点韦恩图及下载交集靶点文件;借助Cytoscape3.7.1构建五苓散潜在活性成分-交集靶点网络,由CytoNCA得到关键靶点;利用关键靶点反向对接得到五苓散关键成分;通过微生信网对关键靶点做GO功能与KEGG通路富集分析,再构建“成分-靶点-通路”网络;利用Sybyl-X2.0对关键成分与关键靶点进行分子对接验证。结果:得到五苓散135个潜在活性成分,包含168个潜在作用靶点,与2111个肥胖T2DM的相关靶点交集后,获得85个共有靶点;拓扑分析得到30个关键靶点,反向对接得到关键成分68个;五苓散治疗肥胖T2DM主要涉及TNF、IL6、INS、IL1B、PTGS2、JUN等靶点;涉及药物应答、细胞间的信号传递、细胞外环境和细包表面、肾上腺素结合、类固醇激素受体活性等过程以及恰加斯病(Chagas disease)、胰岛素抵抗(Insulin resistance)、Toll样受体信号通路(Toll-like receptor signaling pathway)、肿瘤坏死因子信号通路(TNF signaling pathway)等通路;分子对接显示TNF、IL6、INS与27个关键成分有较强的相互作用关系,与4个成分有强烈的相互作用。结论:五苓散治疗肥胖T2DM针对的靶点和通路多与炎症反应和糖脂代谢有关。

Objective:Using network pharmacology and molecular docking technology to explore the mechanism of Wuling San in treating obese type 2 diabetes mellitus(T2DM).Methods:The chemical components and corresponding targets of Wuling San were collected by TCMSP database.The targets related to obese T2DM were sorted out through OMIM,TTD,Drungbank and Disgent databases;Draw Venny maps of component targets and obese T2DM targets on Venny platform and download intersection target file;The network of"potential active components of WulingSan-intersection targets"was constructed with Cytoscape3.7.1,and the key targets were obtained by CytoNCA.The key components were obtained by reverse docking the key target.GO function annotation and KEGG signal pathway enrichment analysis were performed viamicro bioscience network.the"component target pathway"network constructed by Cytoscape 3.7.1 software.Sybyl-x2.0 was used to verify the molecular docking between key components and key targets.Results:135 potential active components of Wuling San were obtained,including 168 potential targets,which were combined with 2111 related targets of obese T2DM,and 85 common targets were obtained.30 key targets were screened by CytoNCA,and 68 key components were obtained by reverse docking.Wuling San mainly involves TNF,IL6,INS,IL1B,PTGS2,JUN and other targets in treating obese T2DM.It involves the processes of drug response,signal transmission between cells,extracellular environment and the surface of sachet,adrenaline binding,steroid hormone receptor activity and other pathways,as well as Chagas disease,Insulin resistance,Toll-like receptor signaling pathway,tumor necrosis factor signaling pathway and so on.Molecular docking showed that TNF,IL-6 and INS had strong interaction with 27 key components and strong interaction with 4 components.Conclusion:The targets and pathways of Wuling San in improving obese type 2 diabetes are mostly related to inflammatory reaction and glucose and lipid metabolism.