基于网络药理学和分子对接技术的西洋参-黄芪治疗2型糖尿病作用机制探究

Mechanism of Panax quinquefolius-Astragalus propinquus in the Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

目的:探究西洋参-黄芪治疗2型糖尿病(T2DM)的作用机制。方法:筛选西洋参-黄芪的有效化学成分与作用靶点、T2DM相关靶点,利用Cytoscape 3.7.2构建中药化学成分-靶点相互作用网络图,筛选出西洋参-黄芪作用T2DM的关键成分和核心靶点。通过DAVID数据库分析核心靶点基因功能及信号通路,构建关键化学成分-核心靶点-信号通路网络,并利用Auto Dock4进行分子对接。结果:通过中药系统药理学数据库与分析平台(TCMSP)及文献检索筛选西洋参-黄芪有效化学成分26种,西洋参9种,黄芪17种,预测靶点184个,与T2DM的靶基因取交集得到靶点162个。中药化学成分-作用靶点相互作用网络共有187个节点,378条连线,筛选出关键成分13种。黄芪关键成分是槲皮素、西洋参关键成分是β-谷甾醇,核心靶点21个与T2DM相关的靶点有PTGS1、PTGS2、NOS2、AR、ERS1、ERS2。核心靶点进行基因本体(GO)富集分析发现西洋参-黄芪主要参与RNA信号转录、唾液分泌、类固醇激素调节等生物过程,京都基因与基因组百科全书(KEGG)富集分析结果显示西洋参-黄芪药对与脂肪细胞内脂肪分解调节、cGMP-PKG信号通路、甲状腺激素信号通路关系密切。分子对接结果显示,β-谷甾醇、槲皮素与核心靶点度值前5位的靶点蛋白(PTGS2、NCOA2、PTGS1、PRSS1、RXRA)有较好的结合性。结论:西洋参-黄芪治疗T2DM的作用机制具有多成分、多靶点、多通路的特点。

Objective:To explore the mechanism of Panax quinquefolius-Astragalus propinquus in the treatment of type 2 diabetes mellitus(T2DM).Methods:The effective chemical components and targets of P.quinquefolius-A.propinquus as well as the targets related to T2DM were screened,and Cytoscape 3.7.2 was used to construct the chemical component-action target interaction network of Chinese medicinal herbs.Then the key components and core targets of P.quinquefolius-A.propinquus acting on T2DM were obtained.The gene functions and signaling pathways of the core targets were analyzed through DAVID.The key chemical components-core targets-signaling pathway network was constructed,and AutoDock4 was used for molecular docking.Results:A total of 26 effective chemical components of P.quinquefolius-A.propinquus were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval,with 9 from P.quinquefolium and 17 from A.propinquus.Additionally,184 targets were predicted,and 162 targets were obtained by intersection with the target genes of T2DM.There were 187 nodes and 378 links in the chemical component-action target interaction network,and 13 key components were selected.The key components of A.propinquus was quercetin and those of P.quinquefolius wasβ-sitosterol.There were 21 core targets,among which,the targets related to T2DM were PTGS1,PTGS2,NOS2,AR,ERS1 and ERS2.GO enrichment analysis of core targets showed that P.quinquefolius-A.propinquus was mainly involved in RNA signal transcription,saliva secretion,steroid hormone regulation and other biological processes,and KEGG enrichment analysis found that P.quinquefolius-A.propinquus was closely related to the regulation of adipocyte lipid decomposition,cGMP-PKG signaling pathway and thyroid hormone signaling pathway.By molecular docking,β-sitosterol and quercetin had good binding to the target proteins(PTGS2,NCOA2,PTGS1,PRSS1,RXRA)in the top 5 core target degree.Conclusion:The mechanism of P.quinquefolius-A.propinquus in the treatment of T2DM has the multi-component,multi-target and multi-pathway characteristics.