Screening of main active ingredients and core target genes of Aconitum episcopale Leveille for the treatment of heart failure and the mechanism of action
LI Jian
LI Yongguo
ZHANG Yunta
YANG Yongcheng
XIA Conglong
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.
Keywords：Aconitum episcopale Leveilleheart failurenetwork pharmacologymolecular docking
Publication Date：2025-04-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 26-31 )