Investigation on the mechanisms of Wuling Powder in treating myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking with experiment verification

LIU Mei-yu; WANG Sheng

摘要：Background Myocardial ischemia-reperfusion injury is characterized by the inability of tissue and organ function to recover after the perfusion blood flow is restored followed by myocardial ischemia.Previous studies have shown that many Chinese herbal compounds can reduce myocardial ischemia-reperfusion injury,but the effi-cacy of Wuling Powder in treating myocardial ischemia-reperfusion injury has not been reported.The present study aimed to investigate the mechanism of Wuling Powder in treating myocardial ischemia-reperfusion injury by network pharmacology and molecular docking.Methods The active constituents of Wuling Powder were ob-tained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the related targets of active constituents of Wuling Powder were screened by the Swiss Target Prediction data-base.Disease targets of myocardial ischemia-reperfusion injury were obtained by GeneCards,DisGeNET and OMIM gene databases.The active compound-target network of Wuling Powder was constructed using Cytoscape software.The drug prediction targets were mapped to the disease target set,and the intersection targets were ob-tained.The Gene Ontology(GO)function and Kyoto Encyclopedia of Genes anf Genomes(KEGG)pathway en-richment analysis were performed on the intersection targets obtained by using String database.AutoDock Vina was used for molecular docking of core targets and the top 3 key active ingredients with degree values.Results Through screening,56 active ingredients and 116 targets of Wuling Powder were obtained.There were 27 com-mon targets of Wuling Powder and myocardial ischemia-reperfusion injury in Myocardial ischemia-reperfusion injury(MIRI).Protein-Protein Interaction(PPI)network analysis in this study showed that CASP3,PTGS2,CAT,JUN,ESR1,CASP8,CASP9 and RELA may be the key targets of Wuling Powder to exert the protective effect of MIRI.GO functional analysis and KEGG pathway enrichment analysis showed that biological processes such as apoptosis,lipopolysaccharide response,steroid hormone response and signal transduction pathways such as PTGS2,TNF-α,nuclear transcription factor-κB(NF-κB),MAPK,PI3K/AKT,NLRP3,and autophagy play an im-portant role in the occurrence and development of MIRI.Molecular docking results showed that β-sitosterol and hederagenin had good binding activities with key targets such as PTGS2,CASP3,and CAT.Conclusions Wul-ing Powder may act on CASP3,PTGS,CAT,JUN,ESR1,CASP8,CASP9 and other targets through β-sitosterol,hederagenin,3β-acetoxyatractylone,taxifolin and other active ingredients.[S Chin J Cardiol 2024;25(3):179-192]