基于网络药理学和分子对接探讨龙加通络胶囊治疗缺血性中风的分子机制  

To Explore the Molecular Mechanism of Longjiatongluo Capsule in the Treatment of Ischemic Stroke Based on Modern Network Pharmacology and Molecular Docking Technology

作　　者：姚尧尧 高颖[1,3] 武艺超 郑湘宜 薛冰洁 YAO Yaoyao;GAO Ying;WU Yichao;ZHENG Xiangyi;XUE Bingjie(Beijing University of Chinese Medicine,Beijing 100029,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学东直门医院,北京100700 [3]国家中医药管理局脑病中医证治重点研究室,北京100700

出　　处：《中西医结合心脑血管病杂志》2023年第15期2735-2742,共8页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家重点研发计划-中医药现代化专项(No.2018YFC1705000,2018YFC1705001);中医药传承与创新“百千万”人才工程(岐黄工程)-国家中医药领军人才支持计划项目,编号:国中医药人教发〔2018〕12号。

摘　　要：目的:基于网络药理学和分子对接探讨龙加通络胶囊治疗缺血性中风物质基础及作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)以及查阅文献获得穿山龙、刺五加的主要活性成分;使用PharmMapper数据库预测活性成分靶点,利用人类基因综合数据库(GeneCards)和在线人类孟德尔遗传数据库(OMIM)得到疾病相关靶点,对活性成分靶点与疾病靶点取交集后采用DAVID数据库进行基因本体(GO)功能以及京都基因与基因组百科全书(KEGG)富集分析。最后通过AutoDock Vina软件对关键靶点和化合物进行分子对接批量处理。结果:筛选出穿山龙、刺五加针对缺血性中风的14个活性成分和179个作用靶点。蛋白质-蛋白质相互作用(PPI)网络拓扑分析发现白蛋白(ALB)、蛋白激酶B1(AKT1)、胱天蛋白酶3(CASP3)、表皮生长因子受体(EGFR)、酪氨酸激酶(SRC)是穿山龙、刺五加治疗缺血性中风的关键靶点。GO功能分析发现龙加通络胶囊生物过程主要集中在中性粒细胞脱粒、RNA聚合酶Ⅱ启动子转录过程的正调控、凋亡过程的负调控等多个方面;KEGG信号富集分析主要涉及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)、有丝分裂原激活蛋白激酶(MAPK)、Ras相关蛋白1(Rap1)等信号通路。分子对接结果显示活性物质与靶点蛋白之间存在较强的结合力,其中薯蓣皂苷与AKT1的结合力最强。结论:穿山龙、刺五加治疗缺血性中风具有多组分、多靶点相互协同的特点,为今后龙加通络胶囊的临床应用提供了理论基础和参考。Objective:To study the mechanism of Longjiatongluo Capsule in the treatment of ischemic stroke(IS)by modern network pharmacology and molecular docking technology.Methods:The main active components of Chuanshanlong and Ciwujia were obtained by traditional Chinese medicine system pharmacology database(TCMSP),comprehensive therapy of Chinese medicine database(TCMID)and literature review.PharmMapper database was used to predict drug targets,disease-related targets were obtained using the comprehensive database of human genes(GeneCards)and the human Mendelian genetic(OMIM)databases.String and DAVID databases were used to perform Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis after the intersection of drug action targets and disease targets.AutoDock Vina software was used to conduct molecular docking batch processing for key targets and compounds.Results:Fourteen active components and 179 targets of Chuanshanlong and Ciwujia for IS were screened out.The protein-protein interaction network(PPI)network topology analysis showed that albumin(ALB),AKT serine/threonine kinase 1(AKT1),cysteinyl aspartate specific proteinase 3(CASP3),epidermal growth factor receptor(EGFR)and sarcoma(SRC)were the key targets of Chuanshanlong and Ciwujia in the treatment of ischemic stroke.GO function analysis showed that the biological processes of Longjiatongluo Capsule mainly focused on neutrophil threshing,positive regulation of RNA polymeraseⅡpromoter transcription and negative regulation of apoptosis.KEGG signal enrichment analysis mainly involves phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt),mitogen-activated protein kinase(MAPK),Ras-associated protein 1(Rap1),and other signaling pathways.The molecular docking results showed that there was a strong binding force between the active substance and the target protein,and the binding force between diosgenin and AKT1 was the strongest one.Conclusion:Chuanshanlong and Ciwujia Show the characteristics of multi-component and multi-target

关 键 词：缺血性中风 龙加通络胶囊 网络药理学 益气活血 分子对接 

分 类 号：R285[医药卫生—中药学]