目的:运用网络药理学和分子对接技术探究冬虫夏草治疗特发性肺间质纤维化(idiopathic pulmonary fibrosis,IPF)的作用机制.方法:通过中药系统药理学数据库与分析平台(traditional Chi-nese medicine systems pharmacology database and analysis platform,TCMSP)筛选出冬虫夏草的主要活性成分及其对应靶点;通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、DrugBank数据库检索获得IPF疾病相关靶点,取二者交集靶点作为冬虫夏草治疗IPF的关键作用靶点;将交集靶点上传至STRING数据库,构建冬虫夏草活性成分与IPF疾病的共同靶点蛋白-蛋白互作网络(protein-protein interactions,PPI),根据度值筛选出核心靶点;将交集靶点基因导入DAVID分析平台,进行基因本体(gene ontology,GO)、京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析.结果:共获得冬虫夏草活性成分7个,作用于IPF的关键靶点84个;关键活性成分有乙酸亚油酯、花生四烯酸、胆固醇、β-谷甾醇,核心靶点有J原癌基因、过氧化物酶体增殖物激活受体γ、丝裂原活化蛋白激酶14等,GO和KEGG富集分析显示主要通路有TNF、VEGF、p53、cAMP、MARK、鞘脂等信号通路,涉及癌症、细胞凋亡、炎症反应等多个生物进程.冬虫夏草活性成分与靶点蛋白可以形成稳定的复合物.结论:冬虫夏草对IPF的治疗作用具有多成分、多靶点、多通路的特点.
The Mechanism of Action of Dongchongxiacao in the Treatment of Idiopathic Pulmonary Fibrosis based on Network Pharmacology and Molecular Docking Technology
Objective:To investigate the mechanism of action of Dongchongxiacao(cordyceps)in the treatment of idiopathic pulmonary fibrosis(IPF)using network pharmacology and molecular docking technology.Methods:The main active ingredients of Dongchongxiacao and their corresponding targets were screened by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP),and IPF-related targets were obtained by searching the human gene database(GeneCards),online mendelian inheritance in man(OMIM)database,and DrugBank database,and the intersection of the two targets was taken as the key target of the medicine in the treatment of IPF.The intersecting targets were uploaded to String database to construct a protein-protein interactions(PPI)network of active ingredients of the medicine and IPF,and the core targets were screened out according to the degree value.The intersecting target genes were imported into DAVID analysis platform for gene ontology(GO),Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:A total of seven active ingredients of the medicine were obtained,and 84 key targets acting on IPF.The key active ingredients were linoleyl acetate,arachidonic acid,cholesterol,β-sitosterol,and the core targets were J proto-oncogene(JUN),peroxisome proliferator-activated receptor γ(PPARG),mitogen-activated protein kinase 14(MAPK14),etc.The GO and KEGG enrichment analyses showed that the main pathways were TNF,VEGF,p53,cAMP,MARK,sphingolipid and other signaling pathways,involving in multiple biological processes such as cancer,apoptosis,and inflammatory response.Active ingredients and target proteins of the medicine can form stable complexes.Conclusion:The therapeutic effects of the medicine on IPF is characterized by multi-components,multi-targets and multi-pathways.
idiopathic pulmonary fibrosisnetwork pharmacologysignaling pathwaymolecular dockingDongchongxiacaomechanism of action
万方数据
维普
