藏药复方玛诺系汤冠心宁浸膏治疗冠心病的潜在分子机制  

Exploring the Molecular Mechanisms Underlying the Therapeutic Effect of Marrbio Decoction Guanxinning Extractum on Coronary Heart Disease

作　　者：东知多杰 佳哇 多杰 周毛吉 才曾卓玛 李啟恩 Dongzhi Duojie;Jia Wa;Duo Jie;Zhou Maoji;Caizeng Zhuoma;Li Qien(Qinghai Institute of Tibetan Medicine,Xining 810016,China;State Key Laboratory of Tibetan Medicine Research and Development,Xining 810016,China)

机构地区：[1]青海省藏医药研究院,西宁810016 [2]藏药新药开发国家重点实验室,西宁810016

出　　处：《青海科技》2022年第6期77-87,共11页Qinghai Science and Technology

基　　金：青海省科学技术厅科技成果转化专项“‘玛诺’系汤系列产品二次开发”(2020-SF-130)。

摘　　要：目的:基于网络药理学方法和分子对接探讨玛诺系汤冠心宁浸膏治疗冠心病(CHD)的潜在分子机制。方法:通过中药系统药理学(TCMSP)数据库、中药综合数据库(TCMID)、PubChem数据库和Swiss Target Prediction数据库检索玛诺系汤冠心宁浸膏的活性成分及其靶点,Genecards、OMIM和Pharm GKB数据库检索冠心病相关靶点;将成分-冠心病共同靶点导入STRING数据库构建蛋白质-蛋白质互作(PPI)网络,并利用Cytoscape软件进行拓扑分析,获取核心成分和核心靶点;通过DAVID数据库对核心靶点进行GO功能和KEGG通路富集分析,最终利用Autodock Vina软件对选择的核心成分和核心靶点进行分子对接。结果 :获得玛诺系汤冠心宁浸膏治疗冠心病的核心成分29个(槲皮素、山奈酚、β-谷甾醇、木犀草素、异鼠李素、熊果酸、熊果醇、鞣花酸等)、核心靶点53个(AKT1、IL6、ALB、VEGFA、MAPK3、TNF、MAPK1、EGFR、SRC、STAT3等),这些核心靶点富集在440个GO条目和109条通路中,主要涉及癌症通路、PI3K/Akt信号通路、MAPK信号通路、Ras信号通路和局部粘附。分子对接结果表明度值排名前10的核心成分和核心靶点均具有良好的结合活性(≤-6.6 kJ/mol),其中熊果酸和熊果醇与TNF、ALB、MAPK3和AKT1结合最稳定。结论 :玛诺系汤冠心宁浸膏可能主要通过黄酮类、萜类、酚类成分参与炎症和氧化应激反应的调节,从而干预冠心病,为进一步验证其作用机制奠定了基础。Objective: To explore the molecular mechanisms underlying the therapeutic effect of Marrbio decoction Guanxinning extractum on coronary heart disease(CHD) based on a systematic network pharmacology approach and molecular docking. Methods: The active components and targets of Marrbio decoction Guanxinning extractum were retrieved from the Traditional Chinese Medicine Systems Pharmacology(TCMSP) database, Traditional Chinese Medicines Integrated Database(TCMID), PubChem database and Swiss Target Prediction database,and CHD related targets were retrieved from the Genecards, OMIM and PharmGKB databases. The common targets of components and CHD were imported into STRING database to construct a protein-protein interaction(PPI) network, and Cytoscape software was used for topological analysis to obtain the core components and core targets. Finally, DAVID database was used for GO function and KEGG pathway enrichment analysis of core targets, and finally molecular docking for selected components and core targets was performed using Autodock Vina software. Results: Twenty-nine core components(quercetin, kaempferol, β-sitosterol, luteolin, isorhamnetin, ursolic acid, uvaol, ellagic acid, etc.) and 53 core targets(AKT1, IL6, ALB, VEGFA, MAPK3, TNF, MAPK1, EGFR, SRC, STAT3, etc.) of Marrbio decoction Guanxinning extractum in the treatment of coronary heart disease were obtained. These core targets were enriched in 440 GO items and 109 pathways, mainly involved in cancer pathways, PI3K/Akt signaling pathway, MAPK signaling pathway, Ras signaling pathway and focal adhesion. Molecular docking results showed that top 10 core components and top 10 core targets by degree values had good binding activity( ≤-6.6 kJ/mol), among which ursolic acid and uvaol were the most stable in binding to TNF, ALB, MAPK3 and AKT1. Conclusion: Marrbio decoction Guanxinning extractum may participate in the regulation of inflammation and oxidative stress response mainly through flavonoids, terpenoids and phenols, thereby intervening coronary heart d

关 键 词：网络药理学 分子对接 玛诺系汤冠心宁浸膏 冠心病 分子机制 

分 类 号：R966[医药卫生—药理学] R972.6[医药卫生—药学]