Timosaponin AIII alleviates type 2 diabetes-induced cardiomyopathy by targeting galectin-3 (LGALS3).

Timosaponin AIII, the main active saponin derived from Anemarrhena asphodeloides Bunge, exerts anti-diabetic effects. However, its underlying mechanism in diabetic cardiomyopathy (DCM) remains unclear. In this study, we explored the pharmacological effects of timosaponin AIII on DCM using a mouse model and H9c2 cells. We found that timosaponin AIII treatment attenuated cardiac remodeling, myocardial fibrosis, and cardiomyocyte apoptosis in high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic mice. Additionally, it significantly reduced galectin-3 expression in HFD/STZ-induced heart tissue and HG-exposed H9c2 cells. Mechanistically, timosaponin AIII facilitated the ubiquitin-dependent degradation of galectin-3. Notably, in timosaponin AIII-treated H9c2 cells, overexpression of galectin-3 significantly restored cardiomyocyte apoptosis and oxidative stress. Taken together, our data confirmed that timosaponin AIII demonstrated cardioprotective effects in diabetic mice by reducing fibrosis and apoptosis. These findings suggest a promising pharmacological strategy for treating DCM.