摘要
目的运用网络药理学和分子对接的方法研究黄山药干预冠心病(coronary heart disease,CHD)的多成分、多靶点、多通路作用机制,旨在为其基础研究及临床应用提供依据。方法通过PharmMapper数据库检索并筛选黄山药的活性成分及作用靶点,利用GeneCards、DisGeNet、OMIM、DRUGBANK筛选冠心病相关靶点,取两者交集靶点;利用STRING11.0获得蛋白互作关系,并通过Cytoscape3.7.2构建PPI网络,MCODE插件分析黄山药干预冠心病关键靶点;采用R3.6.1中的ClsuterProfiler程序包进行GO、KEGG基因富集分析,得到黄山药干预冠心病的潜在作用通路,并利用Cytoscape3.7.2构建成分-靶点-通路图;采用AutoDock Tools 1.5.6、MOE2019进行分子对接研究。结果黄山药中筛选得到10个活性成分,其中涉及冠心病作用靶点62个,MCODE分析最终筛选出10个关键靶点;分子对接验证亦显示评分大于4.25者占总数90%,大于5者占88.3%,即大部分靶点与成分的结合活性较好;KEGG富集分析关键靶点主要被富集在MAPK信号通路、Ras信号通路、PI3K-Akt信号通路、雌激素信号通路、IL-17信号通路等20个显著相关通路,涉及炎症反应、免疫调节等140个显著相关生物过程。结论基于网络药理学探讨了黄山药干预冠心病多成分-多靶点-多通路的作用特点,预测黄山药主要活性成分胡萝卜苷、延龄草苷、新甾体皂苷、progeninⅢ等,可能通过ALB、EGFR、SRC、MAPKs等靶点,作用于MAPK、雌激素、Ras、PI3K/Akt等信号通路干预冠心病,分子对接结果显示,黄山药中的核心化合物胡萝卜苷、延龄草苷、新甾体皂苷、progenin Ⅲ等与主要靶点(ALB、EGFR、SRC、MAPK1)的结合活性较强,为进一步开展黄山药干预冠心病作用机制研究提供了新的思路和方法。
Objective To clarify the multicomponent,multiple targets and multi-channel mechanism of Dioscorea Panthaica Rhizoma in the treatment of the coronary heart disease(coronary heart disease,CHD) by using the method of network pharmacology,so as to provide reference for its basic research and clinical utilization.Methods Firstly,the active components and ideal targets of Dioscorea Panthaica Rhizoma were searched and screened through the database of phammapper,and the related targets of coronary heart disease were screened by GeneCards,DisGeNet,OMIM,and DRGBANK,then the intersecting targets were selected.Secongdly,The String database11.0 was used for protein interaction analysis.A PPI network was built and mcode plug-in was used to analyze the key targets of Dioscorea Panthaica Rhizoma in regulating coronary heart disease by Cytoscape3.7.2 software.Thirdly,the clusterprofiler package in R3.6.1 was used to analyze the gene enrichment of GO and KEGG,and get the potential action pathway of Dioscorea Panthaica Rhizoma in regulating coronary heart disease.Cytoscape 3.7.2 sofeware was used to constmct the the network of drug ingredients-targets-passways",finally it was verified in molecular docking by AutoDock Tools 1.5.6 and MOE2019.Results The number of core active ingredients screened in Dioscorea Panthaica Rhizoma was 10 and 10 ideal targets were finally screened out by mcode analysis in which 62 related targets of coronary heart disease;90% of them scored above 4.25 and 88.3% of them scored above 5,that is to say,the binding activity of most targets and ingredients was good;the key targets of KEGG enrichment analysis were mainly enriched in MAPK signaling pathway,Ras signaling pathway,PI3 K-Akt signaling pathway,estrogen signaling pathway and IL-17 signaling pathway in 20 significant related pathways,involving 140 significant biological processes,such as inflammatory response and immune regulation.Conclusion Dioscorea Panthaica Rhizoma is discussed based on the network pharmacology drug intervention in coronary heart di
作者
但文超
刘红旭
何庆勇
娄妍
蒋燕君
连妍洁
Dan Wenchao;Liu Hongxu;He Qingyong;Lou Yan;Jiang Yanjun;Lian Yanjie(Guang'anmen Hospital,China Academy of Chinese Medical Sciences,Beijing 100053,China;Beijing Hospital of Traditional Chinese Medicine,Capital Medical University,Beijing 100010,China;Graduate School,Beijing University of Chinese Medicine,Beijing 100029,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第6期1829-1843,共15页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
北京市科学技术委员会北京市科技新星计划(Z181100006218035):瓜蒌丹参颗粒对冠心病micro RNA-155及其靶基因调控网络的研究,负责人:何庆勇。
关键词
黄山药
网络药理学
分子对接
冠心病
地奥心血康
Dioscorea Panthaica Rhizoma
Network pharmacology
Molecular docking
Coronary heart disease
Di’ao Xinxuekang(DXK)capsules
