黄芪-当归药对治疗脑梗死的网络药理学研究

A network pharmacology study on Huangqi-Danggui in the treatment of cerebral infarction

目的:通过构建药物与疾病之间的网络关系,探讨黄芪-当归药对治疗脑梗死的作用机制。方法:在中药系统药理学数据库与分析平台(TCMSP)检索黄芪、当归的有效成分及相关靶点,以“cerebral ischemic stroke”及“cerebral infarction”为关键词在GeneCards数据库搜索脑梗死的相关靶点,去除重复项后利用Venny 2.1.0在线工具将药物靶点与疾病靶点取交集,获得黄芪-当归药对治疗缺血性脑卒中的潜在靶点,采用Cytoscape 3.8.2软件构建药物有效成分-疾病靶点调控网络。并利用STRING网站来构建黄芪-当归药对与脑梗死之间的蛋白质-蛋白质相互作用关系网络,并进行相应的基因本体论(GO)富集分析及京都基因和基因组大百科全书(KEGG)信号通路分析,采用Libdock模块对核心成分及关键靶点进行分子对接。结果:从黄芪-当归药对中筛选出共计22个有效成分,与疾病相关的有效成分共计18个,其中黄芪16个,当归2个,核心成分为山柰酚和槲皮素,作用于148个疾病靶点。利用STRING网站来构建黄芪-当归、脑梗死之间的蛋白质-蛋白质相互作用网络,获得核心靶点v-jun禽肉瘤病毒17癌基因同源物(JUN)、丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)1、肿瘤蛋白p53(Tumor Protein p53,TP53)、丝氨酸/苏氨酸激酶1(Akt Serine/Threonine Kinase 1,AKT1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF),经分子对接发现TP53与关键成分槲皮素结合最良好。主要通过剪切应力与动脉粥样硬化通路、磷脂酰肌醇-3-激酶(Phosphatidylinositol 3-kinase,PI3K)-Akt通路、MAPK通路等通路发挥治疗作用。结论:初步预测了黄芪-当归药对治疗脑梗死的有效成分与作用机制,为进一步研究黄芪-当归药对治疗脑梗死的有效成分与作用机制研究奠定了基础。

Objective:To explore the mechanism of Huangqi[Astragalus membranaceus(Fisch.)Bunge]-Danggui[Angelica sinensis(Oliv.)Diels]in the treatment of cerebral infarction by constructing the network relationship between drugs and diseases.Methods:The active components and related targets of astragalus and angelica were searched on the TCMSP platform,and the related targets of cerebral infarction were searched in GeneCards database using the keywords“cerebral ischemic stroke”and“cerebral infarction”.After duplicates were removed,the intersection of drug target and disease target was obtained by Venny 2.1.0 online tool,and the potential target of astragalus-angelica for the treatment of ischemic stroke was constructed by Cytoscape 3.8.2 software.The protein-protein interaction network of astragalus-angelica and cerebral infarction was constructed by STRING,and the corresponding GO enrichment analysis and KEGG signal pathway analysis were carried out.The Libdock module was used for molecular docking of core components and key targets.Results:A total of 22 active components were screened from astragalus-angelica medicine pair,including 18 disease-related active components,among which 16 astragalus and 2 angelica.The core components were kelmanol and quercetin,acting on 148 disease targets.The PPI network of astragalus-angelica and cerebral infarction was constructed by STRING website.The core targets JUN,MAPK1,TP53,AKT1 and TNF were obtained,and TP53 was found to bind best to the key ingredient quercetin by molecular docking.It mainly plays a therapeutic role through shear stress and atherosclerosis pathway,PI3K-Akt pathway,MAPK pathway and other pathways.Conclusion:The effective components and action mechanism of astragalus-angelica in the treatment of cerebral infarction were preliminarily predicted,which laid a foundation for the study of the effective components and action mechanism of astragalus-angelica in the treatment of cerebral infarction in the future.