Astragaloside IV ameliorates cardiomyocyte injury and heart failure through hif/rho/rock pathway regulation: In vitro and in vivo insights

Heart failure represents the culmination of various cardiovascular diseases, distinguished by a spectrum of complex symptoms. Astragaloside IV (AST-IV) has shown significant cardiac protection in heart failure rats, though the mechanisms are not fully understood. This study aimed to investigate the effects of AST-IV using hypoxia-reoxygenation injury in cardiomyocytes and heart failure in rats to explore the effects of AST-IV. Experimental groups were treated with AST-IV, HIF-2α siRNA, or Y-27,632 (a ROCK Inhibitor). Cell proliferation was assessed using CCK-8 and EdU assays, while mitochondrial membrane potential and Apoptosis were evaluated using JC-1 fluorescent probes and TUNEL staining, respectively. Additionally, flow cytometry measured Reactive Oxygen Species and Apoptosis rates, with protein expressions of HIF-2α, RhoB, and ROCK determined via western blotting. Cardiac troponin I and Caspase-3 levels were quantified using ELISA, and myocardial injury was examined through H&E and Masson staining. Results demonstrated that AST-IV notably increased HIF-2α and Rho/ROCK pathway protein expressions, enhancing cell proliferation, reducing Apoptosis and ROS levels, but effects were partially reversible by Y-27,632 in vitro. Our findings suggest that AST-IV mitigates hypoxia-induced cardiomyocyte damage by modulating the HIF/Rho/ROCK pathway, indicating its potential as a therapeutic agent for heart failure.

Astragaloside; HIF-2α; Hypoxia-induced cardiomyocyte injury; ROCK.