Mechanisms of Guanxinning in Myocardial Infarction: An Integrated Approach Using Network Pharmacology, Molecular Docking, and Experimental Validation

Le résumé fourni par la source

Objectives Myocardial infarction (MI) is the most severe manifestation of coronary artery disease. Guanxinning (GXN), a traditional Chinese medicinal compound, is used to treat stable coronary artery disease. However, the potential benefits of GXN in MI and its precise molecular mechanisms remain unclear. This study aimed to explore the effects and therapeutic mechanisms of GXN in MI by network pharmacology, molecular docking, and experimental validation. Methods Using “myocardial infarction” as a search term, we retrieved relevant disease targets from multiple databases, including the Human Mendelian Genetic Disease Database, Drug Database, DisGeNET Database, and GeneCards Human Genetic Synthesis Database. Protein–protein interaction (PPI) networks for the intersecting targets were constructed using the STRING database, and core targets were identified. These were then subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using the Metascape software. Putative active ingredients and core targets were further analyzed by docking and binding energy calculations using AutoDock Vina (Version 1.2.0), and visualization was performed using PyMOL 2.3.0. Additionally, an acute MI rat model was constructed to verify the results of network pharmacology through in vivo experiments. Results Network pharmacology analysis predicted 330 potential therapeutic targets of GXN for the treatment of MI, 26 of which were identified as central to its therapeutic effects. GO enrichment analysis identified 1885 relevant biological processes, whereas KEGG enrichment analysis revealed 154 associated signaling pathways. Imaging studies, enzyme‐linked immunosorbent assays, Western blot analysis, Masson’s trichrome staining, and TUNEL assays demonstrated that GXN mitigated adverse ventricular remodeling by suppressing oxidative stress through activation of the PI3K/AKT/GSK3β signaling pathway. Conclusion GXN effectively suppressed oxidative stress following MI by activating the PI3K/AKT/GSK3β signaling pathway, thereby enhancing cardiac function postinfarction. This study established a theoretical foundation for the potential clinical use of GXN.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.