[关键词]
[摘要]
目的 基于网络药理学探讨麻黄治疗心力衰竭的作用靶点及通路。方法 在TCMSP数据库中筛选麻黄有效成分及作用靶点,通过Uniprot数据库对靶点进行标准化处理。通过GeneCards、OMIM、TTD、Drugbank数据库筛选心力衰竭疾病相关靶点,将药物的作用靶点与疾病靶点进行交集,获得药物-疾病共同靶点,利用STRING数据库进行蛋白质相互作用分析(PPI),并通过Cytoscape3.8.0软件进行拓扑学分析。最后运用Metascape数据平台、David数据库对共同靶点进行GO及KEGG富集分析得出有关信号通路及生物进程。结果 筛选得到麻黄有效成分23个,用来治疗心力衰竭潜在有效成分为木犀草素、槲皮素、β-谷甾醇、山柰酚、豆甾醇、(+)-儿茶素、草质素、柚皮素、飞燕草素、芫花素和乳白蛋白,槲皮素和山柰酚为重要化学成分。麻黄有效成分与心力衰竭共同核心靶点116个,通过PPI拓扑筛选及网络拓扑学分析显示TNF、MAPK1、TP53、IL-6、MAPK3、RELA等16个靶点为主要作用靶点,AGE-RAGE信号通路、流体剪切应力与动脉粥样硬化、MAPK、PI3K-Akt、TNF、IL-17、HIF-1以及细胞凋亡通路等为主要信号通路。结论 麻黄治疗心力衰竭是通过多靶点、多通路的作用,主要体现在调节免疫及炎症因子、抗氧化应激、调控细胞凋亡。
[Key word]
[Abstract]
Objective To explore the targets and pathways of Ephedra Herba in the treatment of heart failure based on network pharmacology. Methods The effective components and targets of Ephedra Herba were screened in the TCMSP database, and the targets were standardized through the Uniprot database. Screening of heart failure disease-related targets through GeneCards, OMIM, TTD, and Drugbank databases, intersecting drug targets with disease targets, obtaining common drug-disease targets, and using STRING database for protein interaction analysis (PPI), and through the Cytoscape 3.8.0 software for topology analysis. Finally, use the Metascape data platform and David database to conduct GO and KEGG enrichment analysis on the common target to obtain the relevant signal pathways and biological processes. Results The results screened 23 active ingredients of Ephedra Herba, and the potential active ingredients used to treat heart failure are luteolin, quercetin, β-sitosterol, kaempferol, stigmasterol, (+) -catechin, herbaceous, naringenin, delphinium, daikon and lactalbumin, quercetin and kaempferol are important chemical components. There are 116 common core targets of Ephedra and heart failure. Through PPI topology screening and network topology analysis, 16 targets such as TNF, MAPK1, TP53, IL-6, MAPK3, RELA, etc. are the main targets, which are related to the AGE-RAGE signaling pathway, fluid shear stress is related to signal pathways such as atherosclerosis, MAPK, PI3K-Akt, TNF, IL-17, HIF-1 and apoptosis pathways. Conclusion The treatment of Ephedra Herba for heart failure is through multiple targets and multiple pathways, which are mainly reflected in the regulation of immune and inflammatory factors, anti-oxidative stress, and regulation of cell apoptosis.
[中图分类号]
R285.5
[基金项目]
国家重点研发计划(2019YFC1710005);国家科技重大专项重大新药创制项目(2018ZX09734-002)