Icariin alleviates cardiomyocyte pyroptosis through AMPK-NLRP3 pathway to ameliorates diabetic cardiomyopathy.

Among the multitude of pressing global health concerns, diabetes mellitus stands out as a significant issue. An alarming consequence of this condition is diabetic cardiomyopathy (DCM), which represents a critical contributor to mortality in individuals with diabetes. Recently, research has unveiled the pivotal role that pyroptosis plays in the progression of myocardial fibrosis associated with DCM. An epimedial flavonoid monomer, Icariin (ICA), primarily sourced from Epimedium genus plants, has shown a safeguarding influence on cardiac health through various means, encompassing anti-inflammatory actions and its capacity against oxidative stress. Our research endeavor focuses on elucidating the beneficial impacts alongside the underlying physiological processes triggered by ICA within the context of DCM. An animal model representative of DCM was developed through intraperitoneal administration of streptozotocin (STZ). In parallel, in vitro experiments utilized H9C2 cardiomyocytes to mimic hyperglycemic environments relevant to disease states. In vivo experiments found that ICA improved cardiac function, alleviated myocardial fibrosis, and reduced NLRP3-mediated pyroptosis in heart tissue of DCM mice. Under in vitro settings characterized by elevated glucose concentrations, there was a notable elevation in both NLRP3 pyroptosis-associated proteins and oxidative stress markers within the heart muscle cells. ICA treatment attenuated pyroptosis and oxidative stress caused by high glucose in cardiomyocytes. Further studies revealed that when treated with an AMPK inhibitor, the shielding benefits conferred by ICA on cardiomyocytes were negated, suggesting that the regulatory effects of ICA on cardiomyocyte pyroptosis may be achieved through the AMPK-NLRP3 pathway. In conclusion, ICA exerts protective effects in DCM by inhibiting cardiomyocyte pyroptosis, alleviating myocardial fibrosis, and improving cardiac function via the AMPK-NLRP3 pathway.