利用网络药理学整合分子对接技术研究人参抗心力衰竭的潜在药效物质基础及作用机制  

Study of the Potential Substance Basis and Mechanism of Action of Ginseng against Heart Failure Using Network Pharmacology Integrated Molecular Docking Technology

作　　者：李昊楠 孔浩天 李晓彬 张姗姗 张轩铭 韩利文 许海玉 刘可春 屠鹏飞[4] Li Haonan;Kong Haotian;Li Xiaobin;Zhang Shanshan;Zhang Xuanming;Han Liwen;Xu Haiyu;Liu Kechun;Tu Pengfei(Engineering Research Center of Zebrafish Models for Human Diseases and Drug Screening of Sh andong Province,Biology Institute,Qilu University of Technology(Shandong Academy of Sciences),Jinan 250103,China;Institute of Materia Medica,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan 256200,China;Institute of Chinese Material Medica,China Academy of Chinese Medical Sciences,Beijing 100700,Chin a;School of Pharmacy,Peking University,Beijing 100700,China)

机构地区：[1]齐鲁工业大学(山东省科学院)山东省科学院生物研究所山东省人类疾病斑马鱼模型与药物筛选工程技术研究中心,济南250103 [2]山东省医学科学院药物研究所/山东第一医科大学,济南256200 [3]中国中医研究院中药研究所,北京100700 [4]北京大学药学院,北京100700

出　　处：《世界科学技术-中医药现代化》2020年第12期4083-4093,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家科学技术部重大共性关键技术(2018YFC1707300):中成药复杂体系高效解析方法和技术研究及其应用,负责人:屠鹏飞;山东省科学技术厅产学研结合项目(2017YQ001):基于高值转化技术的海参副产物新产品研发及产业化示范,负责人:韩利文;山东省科学技术厅医用食品专项计划(2017YYSP032):用于孕期营养补充的固态特医食品制备关键技术及产品研发,负责人:刘可春。

摘　　要：目的利用网络药理学方法整合分子对接技术探究人参治疗心力衰竭的潜在药效物质基础及多靶点多通路的作用机制。方法根据TCMSP数据库和文献收集人参的有效成分,利用Cytoscape 3.6.0软件建立"成分-靶点"网络;在DISGENET数据库和Genecard数据库收集心力衰竭的疾病靶点,建立心力衰竭疾病靶点库和"成分-心衰疾病靶点"网络;通过STRING数据库对人参治疗心衰的靶点进行蛋白质-蛋白质相互作用(PPI)分析,并利用DAVID数据库进行基因本体(gene ontology,GO)富集分析和生物通路(KEGG)富集分析,通过Ledock软件对网络药理学分析结果进行验证。结果本研究涵盖33个人参成分,发现其中山柰酚、人参皂苷Rb1、人参皂苷Rh1、人参皂苷Ro、Fumarine、参皂苷RG、β-谷甾醇均涉及到7个以上靶点,可能是人参发挥抗心衰作用的关键成分;PPI网络拓扑学特征显示STAT3、JUN、IL1B、TNF、MAPK8、VEGFA、PTGS2、NOS2、MMP9等靶点是人参治疗心衰涉及的关键靶点;分子对接的结果也显示了主要的7种活性成分与5种代表性关键靶点的结合性较好。另外人参治疗心衰涉及到了cAMP signaling pathway、TNF signaling pathway、Insulin resistance、Thyroid hormone signaling pathway等55条信号通路。结论本研究从网络药理学角度解析并发现了人参治疗心衰作用的潜在的药效物质,并其对抗心衰作用的分子网络和靶点网络进行了整体解析,揭示了传统中药人参从整体水平多成分、多靶点、多通路的作用特点,为人参治疗心力衰竭的临床应用提供了科学依据。Objective To explore the potential pharmacological basis and multi-target and multi-pathway mechanism of effect of ginseng in the treatment of heart failure using a network pharmacology approach integrating molecular docking techniques. Methods The active ingredients of ginseng were collected from TCMSP database and literatures, and the"ingredient-target"network was established by Cytoscape 3.6.0 software;the disease targets of heart failure were collected from DISGENET database and Genecard database, and the heart failure disease target database and"ingredient-target"network were established. The"component-target"network was established;protein-protein interaction(PPI) analysis of ginseng targets for heart failure was performed in the STRING database, and gene ontology(GO) and biological pathway(KEGG) enrichment analysis was performed in the DAVID database. The results of the network pharmacology analysis were validated by Ledock software. Results This study covered 33 ginseng components and found that kaempferol, ginsenoside Rb1, ginsenoside Rh1, ginsenoside Ro, fumarine, ginsenoside RG, and β-sitosterol were involved in more than 7 targets, which may be key components for ginseng to take on anti-heart failure effects;PPI network topological features showed that STAT3, JUN, IL1 B, TNF, MAPK8, VEGFA, PTGS2, NOS2, and MMP9 are the key targets involved in the treatment of heart failure by ginseng;the results of molecular docking also showed that the main seven active ingredients bind well to five representative key targets. In addition, 55 signaling pathways including cAMP signaling pathway, TNF signaling pathway, Insulin resistance and Thyroid hormone signaling pathway were involved in the treatment of heart failure by ginseng. Conclusion This study analyzed and discovered the potential pharmacological substances of ginseng for the treatment of heart failure from the perspective of network pharmacology, and analyzed the molecular network and target network of its anti-heart failure effect as a whole,revealing th

关 键 词：人参 心力衰竭 网路药理学 分子对接 作用机制 

分 类 号：R274[医药卫生—中医骨伤科学]