Exploring the mechanism of pachymic acid intervention in myocardial ischemia based on network pharmacology and experimental validation

OBJECTIVES: To deeply explore the mechanism of pachymic acid (PA) intervention in myocardial ischemia, providing new ideas and methods for the treatment of myocardial ischemia. METHODS: Predict the targets of PA for improving myocardial ischemia, and conduct functional enrichment analysis using databases, such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome. To verify these findings, PPI network topology analysis and molecular docking were used to screen key targets and main mechanisms of action and further validated through in vitro experiments on the H9C2 cell line. KEY FINDINGS: PA can significantly alleviate myocardial damage caused by hypoxia/reoxygenation, effectively reversing the abnormalities of oxidative stress indicators such as LDH, MDA, SOD, and ROS. PA may exert its effects through 39 targets, particularly by regulating the downregulation of autophagy-related proteins LC3-II and Beclin-1 expression via MTOR, thereby inhibiting excessive autophagy in cardiomyocytes. CONCLUSIONS: PA protects myocardial cells during myocardial ischemia through various pathways, particularly by regulating mTOR to inhibit excessive autophagy.