基于网络药理学及分子对接探讨益气活血方治疗冠心病的作用机制  

The Mechanism of Yiqi Huoxue Formula for Treating Coronary Heart Disease Based on Network Pharmacology and Molecular Docking

作　　者：王琨 杨传华[2] 杨洁[2] WANG Kun;YANG Chuanhua;YANG Jie(Shandong University of Traditional Chinese Medicine,Jinan 250011,Shandong,China)

机构地区：[1]山东中医药大学,济南250011 [2]山东中医药大学附属医院,济南250011

出　　处：《中西医结合心脑血管病杂志》2024年第13期2312-2321,共10页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金面上项目(No.82374385);“泰山学者青年专家”(No.tsqn202211352)。

摘　　要：目的:通过网络药理学方法分析益气活血方治疗冠心病的分子作用机制,并通过分子对接进行验证。方法:通过中药系统药理学数据库与分析平台(TCMSP)和中药分子机制的生物信息学分析工具数据库(BATMAN-TCM)进行检索并筛选出益气活血方中的药物活性成分及作用靶点;在人类基因名片数据库(GeneCards)、人类孟德尔遗传在线数据库(OMIM)、药品数据与药物靶点数据库(DrugBank)、治疗靶点数据库(TTD)检索冠心病对应疾病靶点;通过R语言“Venn”插件得到药物有效活性成分和冠心病的共同靶点基因,应用STRING数据库,获得蛋白质-蛋白质相互作用(PPI)网络图,利用Cytoscape 3.7.2软件中CytoNCA插件筛选候选核心靶点基因,并逆向获得相关有效成分;共同靶点通过R语言“ClusterProfile”等插件,完成基因本体(GO)与京都基因与基因组百科全书(KEGG)富集分析;Cytoscape 3.7.2软件绘制成分-靶点-通路,根据节点筛选核心靶点及成分;利用AutodockTool 4软件对所筛选的核心靶点及成分进行分子对接。结果:筛选得到益气活血方113个主要有效成分,经分子对接验证后,得到治疗冠心病的核心靶点有热休克蛋白90α家族A类成员1(HSP90AA1)、丝氨酸/苏氨酸蛋白激酶B1(AKT1)、雌激素受体1(ESR1)、核因子κB P65(RELA)和半胱氨酸天冬氨酸蛋白酶-3(CASP3),核心成分有槲皮素、山柰酚、木犀草素、异鼠李素和柚皮素。结论:益气活血方中的槲皮素、山柰酚、木犀草素、异鼠李素和柚皮素等有效化学成分,可能通过作用于HSP90AA1、AKT1、ESR1、RELA和CASP3等关键靶点,调节脂质和动脉粥样硬化、流体剪切应力和动脉粥样硬化、晚期糖基化终末产物(AGE)/糖基化终末产物受体(RAGE)信号通路、前列腺癌和白细胞介素(IL)-17信号传导途径等多条信号通路,发挥治疗冠心病的作用。Objective:The molecular mechanism of Yiqi Huoxue formula for the treatment of coronary heart disease were explored and studied by network pharmacology,and verified by the sub-docking.Methods:The active ingredients and targets of Yiqi Huoxue formula were screened by means of Traditional Chinese Medicine(TCM)Systematic Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine(BATMAN-TCM).Disease targets corresponding to coronary heart disease were searched in human GeneCards database(GeneCards),Online Mendelian Inheritance in Man database(OMIM),DrugBank,and Therapeutic Target Database(TTD).The R language"Venn"plug-in was used to obtain the common target genes of drug active ingredients and coronary heart disease.The protein-protein interaction(PPI)network diagram was obtained by STRING database.Cytoscape 3.7.2 software CytoNCA plug-in were used to select candidate core target genes,and the relevant active components were obtained in reverse.Common target through R language"ClusterProfile"and other plug-ins was used to perform enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).Cytoscape 3.7.2 software drawed components-target-pathways and core targets and components were selected by node.AutodockTool 4 software was used for molecular docking of the selected core targets and components.Results:A total of 113 main effective components of Yiqi Huoxue formula were screened.After molecular dock-validation,the core targets for the treatment of coronary heart disease were identified as heat shock protein 90 alpha family class a member 1(HSP90AA1),serine/threonine protein kinase B1(AKT1),estrogen receptor 1(ESR1),nuclear factorκB P65(RELA),and Caspase-3(CASP3).The core components were quercetin,kaempferol,luteolin,isorhamnetin,and naringenin.Conclusion:The active chemical components of quercetin,kaempferol,luteolin,isorhamnetin,and naringenin in Yiqi Huoxue prescription may act on key targets such as HSP

关 键 词：冠心病 益气活血方 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]