Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress

Doxorubicin (DOX) is a classic anti-tumor chemotherapeutic used to treat a wide range of tumors. One major downfall of DOX treatment is it can induce fatal cardiotoxicity. Astragaloside IV (AS-IV) is one of the primary active ingredients that can be isolated from the traditional Chinese herbal medicine, Astragalus membranaceus. This study uses both in vitro and in vivo tools to investigate whether AS-IV alleviates DOX induced cardiomyopathy. We found that AS-IV supplementation alleviates body weight loss, myocardial injury, apoptosis of cardiomyocytes, cardiac fibrosis and cardiac dysfunction in DOX-treated mice. Also, DOX-induced cardiomyocyte injury and apoptosis were effectively improved by AS-IV treatment in vitro. NADPH oxidase (NOX) plays an important role in the progress of the oxidative signal transduction and DOX-induced cardiomyopathy. In this study, we found that AS-IV treatment relieves DOX-induced NOX2 and NOX4 expression and oxidative stress in cardiomyocytes. In conclusion, AS-IV, an antioxidant, attenuates DOX-induced cardiomyopathy through the suppression of NOX2 and NOX4.