基于网络药理学和分子对接方法探讨温阳化饮汤方抗慢性心力衰竭心肌纤维化的作用机制OA

Objective To explore the mechanism of Wenyang Huayin decoction on anti-myocardial fibrosis in chronic heart failure by network pharmacology and molecular docking.Methods Based on the HERB database,we screened the components and therapeutic targets of Wenyang Huayin decoction using Lipinski's five principles and gastrointestinal absorption as the"high".Relevant targets associated with chronic heart failure(CHF)and myocardial fibrosis(MF)were screened using the GeneCards,DisGeNET,OMIM,PharmGKB,TTD,and DrugBank databases.A Venn diagram was constructed to identify intersecting targets between component-related and disease-related genes.A protein-protein interaction(PPI)network was subsequently established using the STRING database,and core targets were identified through topological analysis via the CytoNCA plugin in Cytoscape(version 3.8.0).Furthermore,a"drug-disease-component-target"network was constructed and topologically analyzed using Cytoscape software.To elucidate the biological functions and signaling pathways of the core targets,Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using the DAVID database.Finally,molecular docking simulations were conducted using AutoDock Vina,and the docking results were visualized with PyMol software.Results A total of 744 active ingredients,1330 drug targets,672 CHF and MF targets and 176 intersecting genes were obtained.The core components of TCM were isorhamnetin,quercetin,kaempferol,dibutyl benzene dicarboxylate,and nerolidol acetate.Core targets were SRC,AKT1,TP53,STAT3 and IL6 proteins.GO analysis was mainly enriched in inflammatory response,positive regulation of cell migration,plasma membrane,extracellular region,protein binding,and binding of identical proteins.KEGG major pathways were pathways of cancer,lipids and atherosclerosis,proteoglycans in cancer,PI3K-Akt signaling pathway,and the human cytomegalovirus infection signaling pathway.The results of molecular docking showed that the core components had good binding effects with the core target proteins.Conclusion The mechanism of anti-CHF and anti-MF of Wenyang Huayin decoction may be related to the fact that its four core components act on the core targets of SRC,AKT1,TP53,STAT3 and IL6,modulate multiple pathways,and play a role in inhibiting inflammation,regulating energy metabolism,inhibiting apoptosis,and resisting myocardial fibrosis.