基于网络药理学和分子对接技术探讨健心合剂治疗慢性心力衰竭的作用机制

The Mechanism of Jianxin Mixture for the Treatment of Chronic Heart Failure Based on Network Pharmacology and Molecular Docking Technology

目的:应用网络药理学和分子对接技术探讨健心合剂治疗慢性心力衰竭的作用机制。方法:通过TCMSP数据库检索中药复方健心合剂的中药组分并确定其有效成分,获取有效成分对应的靶蛋白。运用GeneCards、OMIM、PharmGkb、TTD、DrugBank数据库获取慢性心力衰竭相关蛋白;利用STRING数据库探究药物与疾病交集靶点的互作关系,通过Cytoscape-v3.8.2软件筛选核心靶点进行成分-靶点拓扑分析;通过Rx644.0.2软件对交集蛋白进行基因本体(GO)功能富集分析、京都基因与基因组百科全书(KEGG)通路富集分析;采用AutoDock Vina软件对蛋白与成分进行分子对接验证。结果:通过筛选共得到健心合剂166种活性成分、231种中药潜在作用靶点。药物与疾病交集蛋白的核心为RAC-α丝氨酸/苏氨酸-蛋白激酶B(AKT1)、丝裂原活化蛋白激酶1(MAPK1)、肿瘤坏死因子(TNF)等。基因富集分析得到2971条GO功能条目、150条KEGG通路。结果表明,磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(AKT)、TNF等通路与慢性心力衰竭关系密切。分子对接显示,核心蛋白与相应成分之间均具有良好的结合能力。结论:健心合剂中的主要活性成分槲皮素、木犀草素、山柰酚、丹参酮ⅡA、黄芩素、β-谷甾醇可能作用于AKT1、MAPK1、TNF等核心靶点,进而调节PI3K-AKT、TNF等信号通路治疗慢性心力衰竭。

Objective:To explore the mechanism of Jianxin mixture for treating chronic heart failure based on network pharmacology and molecular docking technology.Methods:TCMSP database was used to search the traditional Chinese medicine components in Jianxin mixture and identify the active ingredient,and the corresponding target proteins were obtained.GeneCards,OMIM,PharmGkb,TTD and DrugBank databases were used to obtain chronic heart failure related proteins.The interaction between drug and disease intersection targets was investigated by STRING database,and core targets were screened by Cytoscape-v3.8.2 software for composition-target topology analysis.The gene ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by Rx644.0.2 software.AutoDock Vina software was used to verify the molecular docking between proteins and components.Results:A total of 166 kinds of active ingredients and 231 kinds of potential targets of Chinese medicine were obtained by screening.The core of drug and disease intersection proteins were RAC-αserine/threonine-protein kinase B(AKT1),mitogen-activated protein kinase 1(MAPK1),tumor necrosis factor(TNF).Gene enrichment analysis obtained 2971 GO function terms and 150 KEGG pathways.The results showed that phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)and TNF pathways were closely related to chronic heart failure.Molecular docking showed that the core proteins had good binding ability with the corresponding components.Conclusion:The main active ingredients in Jianxin mixture,such as quercetin,luteolin,kaempferol,tanshinoneⅡA,baicalein andβ-sitosterol,might act on core targets such as AKT1,MAPK1 and TNF,and then regulate PI3K-AKT,TNF and other signaling pathways for the treatment of chronic heart failure.