山东医药2025，Vol.65Issue(4)：26-31,6.DOI:10.3969/j.issn.1002-266X.2025.04.006
西南乌头治疗心力衰竭的主要活性成分和核心靶基因筛选及其机制分析
Screening of main active ingredients and core target genes of Aconitum episcopale Leveille for the treatment of heart failure and the mechanism of action
摘要
Abstract
Objective To screen the main active ingredients and core target genes of Aconitum episcopale Leveille(A.episcopale)for the treatment of heart failure and to analyze their mechanisms,providing new ideas for the treatment of heart failure and the development of drug candidates.Methods The potential target genes of the active ingredients of A.episcopale were screened by searching GenBank and UniProt databases,and the target genes of heart failure-related diseas-es were screened by Human Mendelian Genetic Synthesis Database,Therapeutic Targets Database,GeneCards Database,DisGeNET Database,and DRUGBANK Database,and the intersection of the two was obtained to get the potential target genes of the A.episcopale for the treatment of heart failure.The potential target genes of A.episcopale for the treatment of heart failure were imported into the STRING database,and the protein-protein interaction(PPI)network was constructed,and the PPI network was analyzed by Cytoscape software to screen the core target genes of A.episcopale for the treatment of heart failure.The active ingredients and core target genes for the treatment of heart failure in A.episcopale were import-ed into Cytoscape software to construct a drug-active ingredient-target gene network for the treatment of heart failure in A.episcopale,and the Degree value of each node was calculated by the Analyze Network,and the active ingredients with the top 5 Degree values were selected as the main active ingredients for the treatment of heart failure in A.episcopale.The core target genes were analyzed for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,and the molecular docking technique was used to analysis of the binding efficacy of the main active in-gredient and the core target genes for the treatment of heart failure.Results A total of 819 active ingredient target genes of A.episcopale and 2,221 heart failure disease target genes were screened out,and 326 potential target genes were ob-tained for the treatment of heart failure in A.episcopale after taking the intersection.A total of 21 core target genes were screened out for the treatment of heart failure in A.episcopale by the PPI network,which were STAT3,AKT1,EP300,STAT1,CREBBP,PTPN11,EGFR,MAPK1,ESR1,MAPK3,HIF1A,MAPK14,TP53,PIK3CA,IL6,VEGFA,AR,JAK2,HRAS,MDM2,and RELA.The results of the drug-active ingredient-target gene network analysis showed that the main active ingredients of the A.episcopale for the treatment of heart failure were Bis(2-ethylhexyl)phthalate2,Corytuberine,Glabranin,Corydalmine and 5,7-Dihydroxy-3',4',5'-trimethoxy flavone.The results of GO function and KEEG enrichment analyses showed that the core target genes mainly acted on HIF-1 signaling pathway,PI3K-AKT signal-ing pathway,MAPK signaling pathway and so on.The results of molecular docking showed that the main active ingredients of A.episcopale had better binding efficacy with the core target genes.Conclusion Bis(2-ethylhexyl)phthalate,Corytu-berine,Glabranine,Corydalmine and 5,7-Dihydroxy-3',4',5'-trimethoxy flavone,etc.,which are the main active ingre-dients of A.episcopale,can synergistically regulate the core target genes related to heart failure and exert therapeutic ef-fects on heart failure through multi-targets and multi-pathways.关键词
西南乌头/心力衰竭/网络药理学/分子对接Key words
Aconitum episcopale Leveille/heart failure/network pharmacology/molecular docking分类
医药卫生引用本文复制引用
李剑,李永国,张云塔,杨用成,夏从龙..西南乌头治疗心力衰竭的主要活性成分和核心靶基因筛选及其机制分析[J].山东医药,2025,65(4):26-31,6.基金项目
云南省李剑专家工作站项目(202005AF150013) （202005AF150013）
云南省大理白族自治州科技计划重大项目(D2019NA03). （D2019NA03）
