基于网络药理学及分子对接探讨瓜蒌薤白半夏汤合涤痰汤治疗冠心病的作用机制

Exploration into the mechanism of Gualou Xiebai Banxia Decoction combined with Ditan Decoction on Coronary Atherosclerotic Heart Disease based on network pharmacology and molecular docking

目的探讨瓜蒌薤白半夏汤合涤痰汤治疗冠心病的作用机制。方法运用网络药理学预测作用机制,并用分子对接进行验证。通过中药系统药理学数据库与分析平台(TCMSP)筛选活性成分和预测其对应靶点,检索文献补充活性成分;通过GeneCards、OMIM数据库获得冠心病相关靶点;利用Cytoscape软件构建分析网络,STRING网站分析靶点蛋白的相互作用(PPI),关键靶点在Metascape网站进行基因本体(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析。结果共收集162个活性成分,对应靶点259个,冠心病共同靶点198个;进一步筛选出35个重要成分,73个关键靶点,KEGG富集到最重要的通路是脂质和动脉粥样硬化,其通路上成分与靶点分子对接的结合能均小于-5 kcal/mol。结论脂质与动脉粥样硬化通路是瓜蒌薤白半夏汤合涤痰汤治疗冠心病的重要机制之一,起重要作用的成分为槲皮素、山奈酚、木樨草素等,靶点为AKT1、TNF、IL-6、TP53、IL-1B、PPARG,主要与脂质改善、抗炎、抗氧化应激以及凋亡调节有关。

Objective The aim of the research was to investigate pharmacological mechanism of Gualou Xiebai Banxia Decoction combined with Ditan Decoction(GXBD)on Coronary Atherosclerotic Heart Disease(CAHD).Methods The mechanism of action was predicted by network pharmacology and verified by molecular docking.The components of GXBD were screened and their corresponding targets were predicted through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and supplement the active components by searching the literature.The targets related to CAHD were obtained by GeneCards and OMIM databases.The analysis network was built by Cytoscape software.The protein-protein interaction(PPI)was analyzed by STRING database.GO and KEGG enrichment analyses of core targets were performed on Metascape website.Results A total of 162 active components and 259 corresponding targets were screened and predicted,and 198 common targets of CAHD were obtained.Further analysis screened out 35 important components and 73 core targets.The most important pathway for KEGG enrichment analysis is lipid and atherosclerosis,and the binding energy of the components and targets on the pathway is less than-5 kcal/mol.Conclusion Lipid and atherosclerosis pathway is one of the important mechanisms of GXBD in the treatment of CAHD.The main components are quercetin,kaempferol,luteolin and so on.The targets are AKT1,TNF,IL-6,TP53,IL-1B and PPARG,which are mainly related to lipid improvement,anti-inflammatory,antioxidant stress and apoptosis regulation.