Active ingredients,core target genes screening,and mechanisms of Danggui Buxue decoction in the treatment of myocardial fibrosis
ZHENG Luyao
HAN Yanli
GAO Hongmei
JIN Le
Abstract：Objective To analyze the active ingredients,core target genes,and underlying mechanisms of Danggui Buxue decoction in treating myocardial fibrosis(MF)using network pharmacology and molecular docking technology.Methods The bioactive ingredients of Huangqi(Astragali radix)and Danggui(Angelicae sinensis)in Danggui Buxue decoction were screened using the TCM Systems Pharmacology Database and Analysis Platform(TCMSP)and published literature.The target genes associated with these bioactive ingredients were predicted through the PharmMapper online platform.MF-related disease targets were subsequently screened from the GeneCards,OMIM,and DisGeNET databases.The intersection between ingredient-related targets and MF-related disease targets was obtained,resulting in the identifica-tion of potential therapeutic targets of Danggui Buxue decoction for MF.These targets were imported into the DAVID plat-form for Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway en-richment analyses.A bioactive ingredient-target-pathway network was constructed using CytoScape 3.7.2 software.The top five potential targets ranked by Degree value were identified as core target genes,while the top eight bioactive ingredi-ents ranked by Degree value were selected as core active ingredients.Molecular docking technology was employed to ana-lyze their binding energies.Results A total of 22 bioactive ingredients in Huangqi and 2 bioactive ingredients in Dang-gui were identified.Four hundred and thirty-seven ingredient-related targets and 1,733 MF-related disease targets were screened,from which 166 potential therapeutic targets of Danggui Buxue decoction for MF were obtained through intersec-tion analysis.GO enrichment analysis revealed that the potential targets were associated with 635 biological process terms,160 molecular function terms,and 97 cellular component terms.KEGG pathway analysis demonstrated that these targets were predominantly enriched in the phosphatidylinositol 3-kinase-protein kinase B(PI3K/AKT)signaling pathway,mito-gen-activated protein kinase(MAPK)signaling pathway,and Ras-related protein 1(Rap1)signaling pathway.Eight core bioactive ingredients were confirmed by molecular docking:jaranol,isorhamnetin,quercetin,kaempferol,medicar-pin,3,9-di-O-methylnissolin,isomucronulatol,and stigmasterol.Five core target genes were identified:protein kinase B1(AKT1),epidermal growth factor receptor(EGFR),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic sub-unit α(PIK3CA),mitogen-activated protein kinase 1(MAPK1),and mitogen-activated protein kinase 3(MAPK3).All binding energies were<0 kcal/mol.Notably,the binding energies of isorhamnetin and isomucronulatol with AKT1 were>-5 kcal/mol,while all other binding energies were<-5 kcal/mol.Conclusion Bioactive ingredients in Danggui Buxue decoction,including jaranol,isorhamnetin,and quercetin,exerted therapeutic effects on MF by acting on core tar-get genes such as AKT1,EGFR,PIK3CA,and MAPK1,and regulating the PI3K/AKT signaling pathway and other sig-naling pathways.
Keywords：Danggui Buxue decoctionnetwork pharmacologymolecular docking technologymyocardial fibro-sisjaranolprotein kinase B1epidermal growth factor receptor
Publication Date：2025-06-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 17-22 )