基于网络药理学探讨葛根汤治疗急性脑梗死作用机制

Action Mechanism of Gegen Decoction in Treatment of Acute Cerebral Infarction Based on Network Pharmacology

目的基于网络药理学方法分析葛根汤治疗急性脑梗死的作用机制。方法通过中医药系统药理学数据库与分析平台(TCMSP平台)逐一查询葛根汤所包含的七味中药各自所含主要化学成分、靶点信息,根据ADME筛选中药活性组分,并应用网络图像化软件CytoScape 3.7.2对生物活性成分及作用靶点进行相关网络构建;以急性脑梗死为关键搜索词在Gencards数据库得到相应靶点信息并进行筛选;应用CytoScape 3.7.2中Bisogenet插件构建蛋白质与蛋白质间相互作用网络,将网络提取的关键靶点提交至STRING 11.0数据库,分析其参与的生物学过程。将上述获取的所有药物靶点与所有疾病靶点取交集,利用Metascape数据库进行进一步数据分析,其中包括KEGG通路富集分析、基因功能GO分析等,同时采用平台分析最终获得葛根汤有效成分-急性脑梗死靶点-通路网络图。结果葛根汤治疗急性脑梗死的核心活性成分为槲皮素、地黄黄酮、山柰酚、柚苷配基、β-胡萝卜素、谷固醇、谷甾醇、芒柄花黄素等,核心靶点为ESR1、AR、NOS2、PPARG、PTGS1、F10、SCN5A、DPP4、ADRB2等。葛根汤治疗急性脑梗死的生物学通路主要作用于缺氧诱导因子-1、P53、核因子-κB等信号通路,其功能主要为调节炎症及免疫相关细胞因子的表达。结论葛根汤治疗急性脑梗死的作用机制具有多通路、多靶点、多成分的特点,为葛根汤在临床进一步开发利用提供药理学基础。

Objective To analyze the action mechanism of Gegen Decoction in treatment of patients with acute cerebral infarction(ACI)based on the method of network pharmacology.Methods Chemical components and target informations of each of the seven traditional Chinese medicines contained in Gegen Decoction were retrieved one by one from the traditional Chinese medicine system pharmacology database and analysis platform(TCMSP database),and the active components of traditional Chinese medicine(TCM)were screened according to ADME.The network imaging software Cytoscape 3.7.2 was used to construct the relevant network of biologically active components and targets.Acute cerebral infarction was used as the key search term to obtain corresponding target information in the Gencards database for screening.The Bisogenet plug-in unit of CytoScape 3.7.2 was used to construct a protein-protein interaction(PPI)network,and the key targets extracted from the network were submitted to STRING11.0 database to analyze the biological processes that they involved.After taking the intersection genes of drug targets and disease targets,Metascape database was used to further data analyze which included KEGG pathway enrichment analysis,gene function GO analysis and so on,and the platform analysis was used simultaneously to finally obtain"the effective components of Gegen Decoction-target of ACI-pathway"network chart.Results The core active components of Gegen Decoction in treatment of ACI were Quercetin,Rehmannia Flavone,Kaempferol,Naringin Ligand,β-Carotene,Sitosterol,Sitosterin,Formononetin and so on,and the core targets were ESR1,AR,NOS2,PPARG,PTGS1,F10,SCN5A,DPP4,ADRB2 and so on.The biological pathway of Gegen Decoction in treatment of ACI mainly acted on hypoxia inducible factor-1,p53 and nuclear factor-κB signaling pathways,whose functions were mainly to regulate expressions of inflammation and immune related cytokines.Conclusion The action mechanism of Gegen Decoction in treatment of patients with ACI has the characteristics of multi-pathway,multi-target and multi-component,which provides the pharmacological basis for further development and utilization of Gegen Decoction in clinical practice.