益脑康胶囊治疗缺血性脑卒中的网络药理学机制研究

A Network Pharmacology Approach to Explore Mechanisms of Yinaokang Capsule for Treatment of Ischemic Stroke

目的运用网络药理学方法探究益脑康胶囊治疗缺血性脑卒中(Cerebral ischemic stroke,CIS)的潜在效应机制。方法从中药系统药理学分析平台(TCMSP)及网络药理学分析平台(BATMAN-TCM)数据库中获取益脑康胶囊的化学成分和靶点,通过人类基因数据库(GeneCards)获取缺血性脑卒中的治疗靶点,并利用R语言筛选共同靶点;使用Cytoscape软件构建"药物有效活性成分-疾病靶点"可视化调控网络图,利用STRING数据库构建蛋白互作网络图(PPI),然后运行R语言对PPI进行核心蛋白的筛选;最后,通过R语言对共同靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选出益脑康胶囊36种类药成分及541个潜在靶点,缺血性脑卒中相关靶点1826个,药物-疾病共同靶点245个,GO功能富集分析涉及3052条生物过程,影响对氧化应激的反应、活性氧代谢过程、循环系统血管功能、对细菌源分子的反应、对脂多糖的反应等过程;KEGG通路富集分析得出170条通路,涵盖了PI3K-Akt信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、糖尿病并发症中的AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化信号通路等重要通路。结论益脑康胶囊可能主要通过调节氧化应激、调控细胞功能、改善血管内皮功能来发挥对缺血性脑卒中的治疗作用。

Objective To explore the potential mechanism of Yinaokang capsule in the treatment of cerebral ischemic stroke using a network pharmacology approach.MethodsBased on the TCMSP database and network pharmacology analysis platform(BATMAN-TCM),the effective active components and targets of Yinaokang capsule were extracted,and the targets of cerebral ischemic stroke were obtained through the human gene database(GeneCards),and then the common targets were screened by R language.Cytoscape software was engaged to construct a visual regulatory network map of"drug-active ingredient-disease-target",and a protein-protein interaction network map(PPI)was constructed by using the STRING database.Then the R language was used to screen the core protein of the PPI.Finally,the R language was used to conduct functional gene ontology(GO)enrichment analysis and common enrichment analysis of the Kyoto Gene and Genomic Encyclopedia(KEGG)pathways for common targets.By using network analysis,36 potential bioactive compounds and 541 targets in Yinaokang capsule and1826 cerebral ischemic stroke related targets were identified,resulted in 245 common targets of Yinaokang capsule and ischemic stroke.GO terms were distributed as to 3052 biological processes.The potential mechanism of biological processes and molecular function was related to response to oxidative stress,response to molecule of bacterial origin,response to lipopolysaccharide,reactive oxygen species metabolic process,vascular process in circulatory system and so on.170 signaling pathways were obtained by KEGG enrichment analysis.The core pathways of key targets involved in PI3 K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis and so on.ConclusionThe results of bioinformatics analysis of big data showed that Yinaokang capsule could play an important role in the treatment of ischemic stroke mainly through regulating oxidative stress,cell function,and improving vascular endothelial function.