基于网络药理学和分子对接方法分析黄芪治疗动脉粥样硬化的作用机制

Based on network pharmacology and molecular docking method to analyze the mechanism of Astragalus in treating atherosclerosis

目的探讨基于网络药理学和分子对接方法分析黄芪治疗动脉粥样硬化(As)的作用机制。方法通过TCMSP数据库得到有效成分及对应的靶点基因,利用GeneCards和OMIM数据库获取AS的疾病靶点,构建药物有效成分与疾病靶点的交集Venny图,利用Cytoscape 3.9.1软件与STRING数据库建立有效成分——作用靶点网络和蛋白质互作网络图。通过Metascape平台进行GO功能和KEGG通路富集分析,并采用Autodock软件进行分子对接。结果筛选获得药物有效成分16种,主要的核心成分为槲皮素、山奈酚;药-病交集靶点109个,PPI分析得到蛋白激酶B1(AKT1)、白细胞介素-6(IL-6)、血管内皮生长因子A(VEGFA)、JUN原癌基因(JUN)、白细胞介素1β(IL-1β)5个核心靶点,可能是治疗As的核心靶点。GO生物功能富集分析,获得GO条目共1663个。KEGG通路186条,主要为癌症通路、脂质和As、流体剪切力和As、IL-17等信号通路。分子对接结果显示,黄芪的主要活性成分均能与核心靶点自发结合,其结合能均≤-5.0 kJ/mol。结论黄芪可通过多成分、多靶点、多通路发挥作用而起到抗As的作用,其活性成分具有良好的类药性。为临床应用提供了一定的理论依据。

Objective Based on network pharmacology and molecular docking methods,the mechanism of action of Astragalus in the treatment of atherosclerosis was analyzed.Methods The active ingredient and corresponding target gene were obtained through the TCMSP database.GeneCards and OMIM databases were used to obtain disease targets for atherosclerosis.Construct a Venny diagram of the intersection of drug active ingredients and disease targets.The Cytoscape 3.9.1 software was used to establish the active ingredient-target network and protein interaction network diagram with the STRING database.GO functionality and KEGG pathway enrichment analysis through the Metascape platform.Finally,Autodock software is used for molecular docking.Results 16 kinds of active ingredients of drugs were screened and obtained,the main core ingredients are quercetin and kaempferol.there were 109 drug-disease intersection targets,the five core targets of protein kinase B(AKT1),interleukin 6(IL-6),vascular endothelial growth factor A(VEGFA),Jun proto-oncogene(JUN)and interleukin 1(IL-1β)were obtained by PPI analysis,which may be the core targets for the treatment of atherosclerosis.GO biological function enrichment analysis obtained a total of 1663 GO entries,KEGG pathway 186,mainly cancer pathways,lipid and atherosclerosis,fluid shear and atherosclerosis,IL-17 and other signaling pathways.The molecular docking results showed that,the main active ingredients of Astragalus can spontaneously bind to the core target,and its binding energy is≤-5.0 kJ/mol.Conclusion Astragalus can play an anti-atherosclerosis effect through the function of multi-component,multi-target,and multi-pathway,and the active ingredients have good drug like properties.It provides a certain theoretical basis for clinical application.