多柔比星（DOX）在其强大的抗肿瘤能力和严重的心脏毒性之间引起了矛盾。超菁（Gal）具有抗氧化、抗炎和抗凋亡活性。我们旨在探索Gal在DOX诱导的心脏毒性中的作用和潜在机制。小鼠经腹腔注射DOX（3 mg/kg，每2 天1次，连续2 周）建立心脏毒性模型，并通过灌胃每天共同共同给予Gal（15 mg/kg，连续2 周）。核因子二类红细胞发育相关因子2（Nrf2）特异性抑制剂ML385用于探索潜在机制。与DOX损伤小鼠相比，Gal有效改善心功能障碍并改善心肌损伤。Gal抑制了DOX诱导的活性氧、丙二醛和NADPH氧化酶活性的增加，并抑制了超氧化物歧化酶（SOD）活性的降低。Gal还明显阻断了DOX诱导心脏中IL-1β、IL-6和TNF-α的增加。机制上，Gal逆转了DOX诱导的Nrf2、HO-1的下调，并促进了Nrf2的核转位。ML385显著削弱了Gal的心脏保护效果，以及对氧化应激和炎症的抑制作用。Gal通过激活Nrf2/HO-1信号通路来减轻DOX诱导的心脏毒性，抑制氧化应激和炎症反应。Gal可能成为一种有前途的DOX诱导心脏毒性的心脏保护剂。© 2023 John Wiley＆Sons有限公司。

Doxorubicin (DOX) has aroused contradiction between its potent anti-tumor capacity and severe cardiotoxicity. Galangin (Gal) possesses antioxidant, anti-inflammatory, and antiapoptotic activities. We aimed to explore the role and underlying mechanisms of Gal on DOX-induced cardiotoxicity. Mice were intraperitoneally injected with DOX (3 mg/kg, every 2 days for 2 weeks) to generate cardiotoxicity model and Gal (15 mg/kg, 2 weeks) was co-administered via gavage daily. Nuclear factor erythroid 2-related factor 2 (Nrf2) specific inhibitor, ML385, was employed to explore the underlying mechanisms. Compared to DOX-insulted mice, Gal effectively improved cardiac dysfunction and ameliorated myocardial damage. DOX-induced increase of reactive oxygen species, malondialdehyde, and NADPH oxidase activity and downregulation of superoxide dismutase (SOD) activity were blunted by Gal. Gal also markedly blocked increase of IL-1β, IL-6, and TNF-α in DOX-insulted heart. Mechanistically, Gal reversed DOX-induced downregulation of Nrf2, HO-1, and promoted nuclear translocation of Nrf2. ML385 markedly blunted the cardioprotective effects of Gal, as well as inhibitive effects on oxidative stress and inflammation. Gal ameliorates DOX-induced cardiotoxicity by suppressing oxidative stress and inflammation via activating Nrf2/HO-1 signaling pathway. Gal may serve as a promising cardioprotective agent for DOX-induced cardiotoxicity.© 2023 John Wiley & Sons, Ltd.