摘要
Cerebral ischemia(CI)is the world’s second-largest lethal disease,with a high recurrence and teratogenic rate.Traditional Chinese medicine(TCM)YQHX(a pharmaceutical preparation from herbs)has a certain effect in the clinical treatment of CI,while its underlying mechanism remains largely undetermined.To explore the potential mechanism,we used network pharmacology and molecular docking in the present study.TCMSP and CNKI databases were used to explore the active ingredients of YQHX;the Pharmmapper database was used to get the ingredient targets;the OMIM,GeneCards,and DisGeNET databases were used to obtain the disease targets;the Venn diagram was used to obtain the intersection targets,the Cytoscape was used to visualize results and plug-in MCODE to obtain core targets;the Metascape database was used to perform GO and KEGG pathway enrichment analyses on core targets.The top 20 KEGG pathway enrichment pathways were used to construct the“ingredient-target-pathway”network by Cytoscape;the top 10 ingredients and the top five protein targets were used for molecular docking with AutoDock Vina software,and PyMoL and Ligplus software were used to visualize the results.A total of 83 active ingredients were screened from YQHX.Moreover,432 corresponding targets,2005 disease-related targets,and 140 drug-disease intersection targets were obtained.GO biological function and KEGG pathway enrichment analyses yielded 507 biological function entries and 141 signaling pathways.KEGG pathway enrichment was mainly involved in cell proliferation,adhesion,migration,and other processes.Molecular docking results showed that the key ingredients and core targets screened had a strong binding activity,including EGFR,MAP2K1,and KDR.The combination of miltionone I and miltiodiol was relatively stable.The main biological mechanism of YQHX in the treatment of CI might play a role through the signaling pathway related to the tyrosine kinase receptor,which was also the improvement of the theory of“benefiting qi and activating blood circulatio
脑缺血(cerebral ischemia,CI)具有高发病率、高致畸率,是全球第二大致死疾病。中药(traditional Chinese medicine,TCM)益气活血方(YQHX)在临床治疗CI发挥一定疗效,但其机制尚不清楚。本文基于网络药理学和分子对接探讨其作用机制。通过TCMSP和CNKI数据库获取益气活血方活性成分;利用Pharmmapper数据库获得成分靶点信息;检索OMIM、Gene Cards、DisGeNET数据库得到脑缺血的疾病靶点;Venn图得到交集靶点,Cytoscape可视化结果,插件MCODE获得核心靶点;使用Metascape数据库对核心靶点进行GO和KEGG通路富集分析;选取前20条KEGG通路富集通路用Cytoscape构建“成分-靶点-通路”图;排名前10的成分与前5的靶点信息,利用AutoDockVina软件进行分子对接验证,用PyMoL、Ligplus软件可视化结果。筛选得到益气活血方活性成分83个,相应靶点432个,疾病相关靶点2005个,药物与疾病的交集靶点140个;通过GO生物功能分析和KEGG通路富集分析得到507条生物功能条目及141条信号通路。KEGG通路富集分析主要参与细胞增殖、粘附、迁移等过程;分子对接结果显示,筛选的关键成分与核心靶点皆具备较强的结合活性,其中EGFR、MAP2K1、KDR与丹参新酮I、丹参酮二酚结合较为稳定。益气活血方治疗脑缺血主要生物学机制可能通过酪氨酸激酶受体相关的信号通路发挥作用,也是对中医“益气活血,血脉新生”理论的完善。
基金
General program of National Natural Science Foundation of China(Grant No.81573941)
Open fund project for first-class disciplines of traditional Chinese Medicine(Grant No.2021ZYX20)
Graduate research innovation project of Hunan Province(Grant No.CX20200798)。
