Calycosin Alleviates MIRI by Regulating Inflammation and Angiogenesis: A Network Pharmacology and Experimental Study

Background Calycosin, the primary active compound of Astragalus membranaceus, has demonstrated potential protective effects against myocardial ischemia–reperfusion injury (MIRI). However, its underlying molecular mechanisms remain incompletely understood. Purpose This study aimed to investigate the potential mechanisms underlying the protective effects of calycosin against MIRI using network pharmacology, molecular docking, and in vitro experimental validation. Methods Calycosin-associated targets were retrieved from the STITCH, TCMSP, HERB, and SwissTargetPrediction databases, while MIRI-related targets were collected from GeneCards, OMIM, and DrugBank. Core targets were identified through protein–protein interaction (PPI) network construction and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the associated biological processes and signaling pathways. A drug–target–signaling pathway network was constructed, and molecular docking was conducted to evaluate the interactions between calycosin and key targets. Finally, the effects of calycosin on H9C2 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R) were investigated using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results PPI network topology analysis identified 37 core targets. GO and KEGG enrichment analyses revealed that these targets were primarily associated with inflammation and angiogenesis. Molecular docking demonstrated favorable binding affinities between calycosin and key targets, including AKT1, SRC, STAT3, IL6, IL1β, and MAPK1, with binding energies below −6.0 kcal/mol. In OGD/R-treated H9C2 cells, calycosin significantly increased the mRNA expression of AKT1, SRC, and STAT3 while decreasing the mRNA expression of IL6, IL1β, and MAPK1. Conclusion Calycosin may exert protective effects against MIRI through multiple molecular targets and signaling pathways, potentially involving anti-inflammatory and angiogenesis-related mechanisms. These findings provide a theoretical basis for further mechanistic investigation and in vivo validation of calycosin as a potential therapeutic agent for MIRI.