[關鍵詞]
[摘要]
目的 基于網(wǎng)絡藥理學探討麻黃治療心力衰竭的作用靶點及通路。方法 在TCMSP數(shù)據(jù)庫中篩選麻黃有效成分及作用靶點,通過Uniprot數(shù)據(jù)庫對靶點進行標準化處理。通過GeneCards、OMIM、TTD、Drugbank數(shù)據(jù)庫篩選心力衰竭疾病相關靶點,將藥物的作用靶點與疾病靶點進行交集,獲得藥物-疾病共同靶點,利用STRING數(shù)據(jù)庫進行蛋白質(zhì)相互作用分析(PPI),并通過Cytoscape3.8.0軟件進行拓撲學分析。最后運用Metascape數(shù)據(jù)平臺、David數(shù)據(jù)庫對共同靶點進行GO及KEGG富集分析得出有關信號通路及生物進程。結(jié)果 篩選得到麻黃有效成分23個,用來治療心力衰竭潛在有效成分為木犀草素、槲皮素、β-谷甾醇、山柰酚、豆甾醇、(+)-兒茶素、草質(zhì)素、柚皮素、飛燕草素、芫花素和乳白蛋白,槲皮素和山柰酚為重要化學成分。麻黃有效成分與心力衰竭共同核心靶點116個,通過PPI拓撲篩選及網(wǎng)絡拓撲學分析顯示TNF、MAPK1、TP53、IL-6、MAPK3、RELA等16個靶點為主要作用靶點,AGE-RAGE信號通路、流體剪切應力與動脈粥樣硬化、MAPK、PI3K-Akt、TNF、IL-17、HIF-1以及細胞凋亡通路等為主要信號通路。結(jié)論 麻黃治療心力衰竭是通過多靶點、多通路的作用,主要體現(xiàn)在調(diào)節(jié)免疫及炎癥因子、抗氧化應激、調(diào)控細胞凋亡。
[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.
[中圖分類號]
R285.5
[基金項目]
國家重點研發(fā)計劃(2019YFC1710005);國家科技重大專項重大新藥創(chuàng)制項目(2018ZX09734-002)