Abstract
Cardiotoxicity linked to doxorubicin (DOX) is primarily caused by inflammation, oxidative stress, and apoptosis. The role of tubeimoside I (TBM) in DOX-induced cardiotoxicity remains ambiguous, despite growing evidence that it could reduce inflammation, oxidative stress, and apoptosis in various diseases. This study was designed to investigate the role of TBM in DOX-induced cardiotoxicity and uncover the underlying mechanisms. H9c2 cell line and C57BL/6 mice were used to construct an in vitro and in vivo model of DOX-induced myocardial injury, respectively. We observed that DOX treatment provoked inflammation, oxidative stress, and cardiomyocyte apoptosis, which were significantly alleviated by TBM administration. Mechanistically, TBM attenuated DOX-induced downregulation of sirtuin 3 (SIRT3), and SIRT3 inhibition abrogated the beneficial effects of TBM both in vitro and in vivo. In conclusion, TBM eased inflammation, oxidative stress, and apoptosis in DOX-induced cardiotoxicity by increasing the expression of SIRT3, suggesting that it holds great promise for treating DOX-induced cardiac injury.