基于网络药理学和分子对接技术探究桂枝汤治疗慢性心力衰竭的作用机制OACSTPCD

OBJECTIVE:Utilizing network pharmacology and molecular docking techniques to investigate the therapeutic mechanism of Guizhi Decoction in chronic heart failure.METHODS:The main practical components and targets of Guizhi Decoc-tion were screened by the BATMAN-TCM database.We used the GeneCards and DisGENET databases to identify target genes re-lated to chronic heart failure.Using the Venny platform,we performed a joint gene screening between traditional Chinese medicine and the disease.We employed Cytoscape 3.7.2software for visual analysis,creating a"disease-drug-component-target"network diagram to identify core active components.We constructed a protein-protein interaction(PPI)network diagram using the String database to identify core targets.Subsequently,we conducted gene ontology(GO)function with Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis using the DAVID database.Finally,we utilized the Autodock software for molec-ular docking of core components and targets.RESULTS:We identified 215active components associated with Guizhi Decoction a-long with a total of 1873unique drug targets.Simultaneously,we identified 2426disease-related targets associated with chronic heart failure,with 599genes common to both traditional Chinese medicine and the disease.In the"Traditional Chinese Medicine-disease-active components-targets"network,the core active components included Zingiberone,Shyobunone,Betulin,Coprine,and Nonanoic Acid.Protein-protein interaction(PPI)network analysis revealed core targets,including AKT1,INS,IL-6,TNF,and TP53.Gene ontology(GO)enrichment analysis suggested that Guizhi Decoction may potentially treat chronic heart failure by regulating processes related to the muscular system,blood circulation,and drug responses.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis results indicated that the therapeutic effectiveness of Guizhi Decoction might be associated with pathways such as HIF-1 signaling,cAMP signaling,FoxO signaling,and calcium signaling pathway.The molecu-lar docking results indicated that the top three components,based on their absolute binding energy,were betulin with AKT1(-5.7kcal/mol),Zingiberone with IL-6(-5.5kcal/mol),and botulin with IL-6(-5.4kcal/mol).Conclusion:The mechanism of action of Guizhi Decoction may involve active components such as Zingiberone,Shyobunone,Betulin,Coprine,and Nonanoic Acid.These components may potentially modulate multiple pathways,which include HIF-1 signaling pathway,FoxO signaling pathway,cAMP signaling pathway,and calcium signaling pathway.This modulation,in turn,may affect relevant targets such as AKTland IL6,offering a potential treatment approach for chronic heart failure.