基于网络药理学和分子对接技术探讨四妙勇安汤治疗冠心病的作用机制

The Mechanism of Simiao Yongan Decoction in the Treatment Coronary Heart Disease Based on Network Pharmacology and Molecular Docking

目的:基于网络药理学和分子对接技术探讨四妙勇安汤治疗冠心病(CHD)的潜在作用机制。方法:应用中药系统药理学技术平台(TCMSP)筛选四妙勇安汤的药物有效活性成分及作用靶点,应用全球蛋白质资源(UniProt)数据库对基因标准化处理。通过GeneCards数据库和在线人类孟德尔遗传(OMIM)数据库检索冠心病的有关靶点,将药物有效活性成分靶点与冠心病的相关靶点进行映射,取交集即为四妙勇安汤治疗冠心病的潜在靶点。使用Cytoscape 3.7.2软件构建四妙勇安汤治疗冠心病的“药物-成分-疾病-靶点”网络图,运用生物分子功能注释系统(STRING)数据库及Cytoscape 3.7.2软件构建蛋白-蛋白互作(PPI)网络图,并筛选核心靶点。利用DAVID数据库对得到的交集靶点进行基因本体(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,并利用AutoDock及PyMOL等软件进行分子对接验证及结果的可视化分析。结果:共得到四妙勇安汤治疗冠心病的活性成分127个、相关靶点137个、交集靶点120个。四妙勇安汤治疗冠心病的生物过程涉及对缺氧的反应、一氧化氮生物合成过程的积极调节、细胞外空间、酶结合、类固醇激素受体活性等;四妙勇安汤治疗冠心病可能与肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)信号通路、缺氧诱导因子-1(HIF-1)信号通路、钙信号通路、环磷酸鸟苷酸-环磷酸鸟苷酸依赖的蛋白激酶(cGMP-PKG)信号通路等有关。分子对接结果显示,四妙勇安汤的8个关键活性成分与5个核心蛋白均有较好的结合能力。结论:四妙勇安汤的有效活性成分通过作用于多靶点、多通路治疗冠心病,为进一步的研究奠定基础。

Objective:To explore the potential mechanism of Simiao Yongan Decoction in the treatment of coronary heart disease based on network pharmacology and molecular docking.Methods:The active ingredients and related targets of Simiao Yongan Decoction were screened by Traditional Chinese Medicine Systematic Pharmacology Platform(TCMSP)database,and the genes were standardized by the global protein resources(UniProt)database.The related targets of coronary heart disease were obtained by searching online OMIM database and GeneCards database,and the targets of the effective active ingredients of drugs were mapped with the relevant targets of coronary heart disease,and the obtained mapping targets were the potential targets of Simiao Yongan Decoction in treating coronary heart disease."Drug-component-disease-target"network map in the treatment of coronary artery disease with Simiao Yongan Decoction was constructed by Cytoscape 3.7.2 software,and protein-protein interaction(PPI)network map was constructed by the STRING database and Cytoscape 3.7.2 software,and core targets were screened.Genetic Ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the obtained intersection targets using DAVID database.Validation of molecular docking and visualization of results were used by AutoDock and PyMOL software.Results:A total of 127 active ingredients,137 related targets and 120 intersecting targets of Simiao Yongan Decoction in the treatment of coronary heart disease were screened out.The biological process of treating coronary heart disease by Simiao Yongan Decoction involved reaction to hypoxia,active regulation of nitric oxide biosynthesis,extracellular space,enzyme binding,steroid receptor activity.The treatment of coronary heart disease with Simiao Yongan Decoction might be related tumor necrosis factor(TNF)signaling pathway,phosphatidylinositol 3-kinase(PI3K-Akt)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,calcium signaling pathway,cyclic guanosine monophosphate/cyclic guanosine monophosphate-dependent protein kinase(cGMP-PKG)signaling pathway.The results of molecular docking showed that 8 key active ingredients of Simiao Yongan Decoction showed better binding ability to 5 core proteins.Conclusion:The active ingredients in Simiao Yongan Decoction regulate multiple pathways to treat coronary heart disease by acting on multiple targets,this would supply the foundation for further research.