Astragaloside IV inhibits adriamycin-induced cardiac ferroptosis by enhancing Nrf2 signaling

Astragaloside IV (AsIV), an active ingredient isolated from traditional Chinese medicine astragalus membranaceus, is beneficial to cardiovascular health. This study aimed to characterize the functional role of AsIV against adriamycin (ADR)-induced cardiomyopathy. Here, healthy rats were treated with ADR and/or AsIV for 35 days. We found that AsIV protected the rats against ADR-induced cardiomyopathy characterized by myocardial fibrosis and cardiac dysfunction. Meanwhile, ADR increased type I and III collagens, TGF-beta, NOX2, and NOX4 expression and SMAD2/3 activity in the left ventricles of rats, while those effects were countered by AsIV through suppressing oxidative stress. Moreover, ADR was found to promote cardiac ferroptosis, whereas administration of AsIV attenuated the process via activating Nrf2 signaling pathway and the subsequent GPx4 expression increasing. These results suggest that AsIV might play a protective role against ADR-induced myocardial fibrosis, which may partly attribute to its anti-ferroptotic action by enhancing Nrf2 signaling.