Network pharmacology and molecular dynamics study of Astragalus membranaceus-Salvia miltiorrhiza in the treatment of myocardial ischemia-reperfusion injury

Myocardial ischemia-reperfusion injury (MIRI) represents a significant complication associated with revascularization treatment for individuals experiencing a myocardial infarction. Studies have demonstrated that both Astragalus membranaceus and Salvia miltiorrhiza (AS) exhibit cardioprotective properties. This study investigates the potential mechanisms of AS in treating MIRI through network pharmacology, molecular docking, and molecular dynamics simulations. In this investigation, the active compounds and their corresponding targets linked to AS were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP), as well as from the PubChem and SwissTargetPrediction databases, while the target genes for MIRI were sourced from the GeneCards and OMIM databases. A protein–protein interaction network was created using STRING and Cytoscape to identify core targets. Utilizing the DAVID database, enrichment analyses through gene ontology and the kyoto encyclopedia of genes and genomes were performed to clarify pathways associated with the therapeutic application of AS in managing MIRI. AutoDockTools was utilized to assess the binding affinity of key bioactive compounds with major targets, complemented by molecular dynamics simulations using GROMACS. Results indicated that AS contains 85 bioactive compounds, 803 drug–target genes, and 1451 disease targets, with 136 intersecting targets and 28 core targets identified. Molecular docking results showed that the core targets successfully docked with major pharmacological components, with more stable binding observed between AKT1 and luteolin, PTGS2 and luteolin, PTGS2 and kaempferol. Molecular dynamics simulation results indicated good stability. Through the utilization of network pharmacology, molecular docking, and molecular dynamics simulations, this research establishes that AS can deliver therapeutic benefits for MIRI by acting on various components, targets, and pathways, thereby offering a theoretical basis for future investigations and clinical implementations.