Astragaloside IV Attenuates Arsenic-Induced Myocardial Injury and Reduces Galectin-3 Expression: A Network Toxicology and In Vivo Study

Arsenic-induced myocardial injury (AIMI) is a cardiovascular consequence of arsenic exposure. Astragaloside IV (AS-IV), a primary bioactive compound from Astragalus membranaceus, is known for its cardioprotective properties, yet its efficacy against AIMI remains unexplored. This study combined network toxicology, molecular docking, molecular dynamics simulations, and in vivo experiments to assess AS-IV’s protective effects and potential mechanisms in AIMI. We identified 101 overlapping targets between AS-IV and AIMI. Functional enrichment implicated apoptosis-related processes and inflammatory pathways in AS-IV’s actions. Five hub genes—LGALS3, MMP9, IL2, AR, and BCL2L1—were identified. Docking and simulations predicted potential interactions of AS-IV with MMP-9 and galectin-3 (encoded by MMP9 and LGALS3). In vivo, AS-IV ameliorated arsenic-induced histopathological damage and reduced cTnI levels. Arsenic exposure decreased myocardial GSH-Px activity but increased T-SOD activity, whereas MDA levels showed no statistically significant changes across groups. AS-IV restored GSH-Px activity and further increased T-SOD activity without significantly altering MDA levels. In addition, AS-IV attenuated cardiomyocyte apoptosis, as evidenced by reduced TUNEL positivity and cleaved caspase-3 expression. Notably, arsenic upregulated galectin-3, which AS-IV dose-dependently reduced, while MMP-9 remained unchanged in this early-stage model, consistent with minimal fibrosis. Further bioinformatic analyses linked galectin-3 to early immune-inflammatory and extracellular matrix remodeling signals. In conclusion, AS-IV attenuated arsenic-induced myocardial injury and cardiomyocyte apoptosis in mice. The protective effects were accompanied by changes in oxidative stress-related enzyme activities and reduced myocardial Galectin-3 expression. These findings suggest that galectin-3 may represent a candidate target associated with AS-IV treatment, although its causal involvement in the cardioprotective effects of AS-IV requires further investigation.