摘要
目的:利用网络药理学与分子对接技术预测青蒿素治疗动脉粥样硬化(AS)的作用机制。方法:运用中药系统药理学数据库与分析平台(TCMSP)、PubChem和Swiss Target Prediction数据库获取青蒿素的作用靶点,从GeneCards、DisGeNET平台获取与AS相关的靶点,通过基因映射得到青蒿素干预AS的靶点。采用DAVID数据库对靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)富集分析,并利用微生信平台进行可视化。利用String数据库和Cytoscape3.10.0软件构建蛋白质-蛋白质相互作用(PPI)网络,并进行聚类分析及网络拓扑属性分析筛选出关键靶点,之后构建中药成分-靶点-通路-疾病网络,选出与疾病通路关联较多的关键靶点。最后通过AutoDock软件将青蒿素和靶点进行分子对接,依据结合能评价结合活性。结果:共获得青蒿素靶点109个,AS靶点1217个,青蒿素干预AS的靶点35个。GO富集分析提示青蒿素干预AS的靶点主要参与了信号转导、异生物质的新陈代谢、细胞增殖的正向调控等生物过程(BP),与质膜、细胞质、大分子复合物等细胞组分(CC)相关,涉及类固醇羟化酶活性、蛋白激酶活性、氧化还原酶活性等分子功能(MF)。KEGG富集分析表明青蒿素干预AS的靶点主要干预了丝裂原活化蛋白激酶(MAPK)信号通路、松弛素信号通路、癌症信号通路、流体剪切应力(FSS)与AS、肾素-血管紧张素(Ras)信号通路等与AS治疗相关的通路。分子对接结果表明青蒿素与靶点MAPK8、表皮生长因子受体(EGFR)、MAPK14之间具有良好的结合力。结论:青蒿素可能通过干预MAPK信号通路、松弛素信号通路、癌症信号通路、流体剪切应力与AS、Ras信号通路等实现对AS的治疗作用,MAPK8、EGFR、MAPK14可能是青蒿素治疗AS的核心靶点。
Objective:To predict the mechanism of Artemisinin in treating atherosclerosis(AS)by using networks pharmacology and molecular docking.Methods:Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),PubChem database and Swiss Target Prediction database,the effect targets of Artemisinin were obtained,and the AS-related targets were obtained from GeneCards and DisGeNET,and the targets intervening AS by Artemisinin were obtained by gene shine.Using DAVID database,the targets were given enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)and visualized by Wei Sheng Xin.The protein-protein interaction(PPI)networks were established by String database and Cytoscape3.10.0 software,and the critical targets were screened out by the cluster analysis and network topology analysis.Then the ingredient of Chinese medicinals-targets-pathways-disease network was established and the critical targets mainly related to disease pathway were selected.The molecular docking of Artemisinin and targets was conducted through AutoDock software and the binding activity was evaluated according to binding energy.Results:A total of 109 targets of Artemisinin,1217 AS targets and 35 targets intervening AS by Artemisinin were obtained.The GO enrichement analysis pointed out that the targets intervening AS by Artemisinin mainly participated in the signal transduction,metabolism of xenobiotics,positive regulation of cell proliferation and other biological processes(BP),related to the cell components(CC)of plasmalemma,cytoplasm and macromolecular compound and involving the molecular functions(MF)of cholesterol-hydroxylase activity,protein kinase activity and oxidation enzyme activity.The KEGG enrichment analysis suggested that the targets intervening AS by Artemisinin mainly intervened the signaling pathways related to the treatment of AS,including the signaling pathway of mitogen-activated protein kinase(MAPK),relaxin signaling pathway,cancer signaling pathway,fluid shear stress(FSS),AS and signaling pathway of reninangiotensin system(Ras).According to the results of molecular docking,it showed that there was great binding force between Artemisinin and targets of MAPK8,endothelial growth factor receptor(EGFR)and MAPK14.Conclusion:Artemisinin may achieve the curative effect on AS through intervening MAPK signaling pathway,relaxin signaling pathway,cancer signaling pathway,FSS,AS and Ras signaling pathway,and the MAPK8,EGFR and MAPK14 are the core targets for treating AS with Artemisinin.
作者
杨敏
叶敏
邓超平
卢健棋
YANG Min;YE Min;DENG Chaoping;LU Jianqi(FangChengGang Hospital of Traditional Chinese Medicine,Fangchenggang Guangxi 538021,China;Cardiovascular WardⅠof the First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning Guangxi 530023,China)
出处
《新中医》
2025年第4期149-155,共7页
New Chinese Medicine
基金
国家自然科学基金地区科学基金项目(82160887)
广西中医特色优势重点项目—肾病科(CZXM-02-106)
广西医疗卫生适宜技术研究与开发项目(S201532)。
作者简介
杨敏(1996-),女,硕士,住院医师,E-mail:498507364@qq.com;邓超平(1993-),男,硕士,住院医师,E-mail:943251060@qq.com;卢健棋(1963-),男,主任医师,教授,E-mail:lujianqi666@163.com;通信作者:叶敏(1982-),男,硕士,副主任医师,E-mail:yangmaim@126.com。
