Astragalin attenuates doxorubicin-induced cardiotoxicity in rats by regulating mitochondrial function and oxidative stress

Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in its long-term clinical application due to its pronounced cardiotoxicity. Currently, effective strategies for the prevention and treatment of DOX-induced cardiotoxicity remain insufficient. This study aimed to investigate whether astragalin (AST) alleviates DOX-induced cardiotoxicity in rats by modulating mitochondrial function and oxidative stress, thereby providing a theoretical basis and potential therapeutic approach for clinical application. Fifty male Sprague-Dawley rats were randomly assigned into five groups (n = 10 per group): Group A (vehicle control, saline), Group B (DOX), Group C (DOX + 10 mg/kg AST), Group D (DOX + 20 mg/kg AST), and Group E (20 mg/kg AST alone). Histopathological changes in myocardial tissue were assessed by hematoxylin-eosin (H&E) staining. The mRNA expression levels of Bax and Bcl-2 were measured using real-time quantitative PCR (RT-qPCR). Cell viability was assessed via the CCK-8 assay, while apoptosis was evaluated using TUNEL staining. Intracellular reactive oxygen species (ROS) levels were measured with the DCFH-DA fluorescent probe. Mitochondrial membrane potential (MMP) was detected using flow cytometry. Protein expression levels in myocardial tissues and cultured cells were analyzed by Western blotting. Pretreatment with AST significantly reduced serum troponin and creatine kinase-MB (CK-MB) levels in DOX-treated rats ( P < 0.05), decreased the proportion of TUNEL-positive apoptotic cells, reduced intracellular ROS accumulation, and mitigated MMP loss ( P < 0.05). AST also reversed the DOX-induced alterations in Bax and Bcl- 2 mRNA expression ( P < 0.05), attenuated the decline in cell viability ( P < 0.05), increased intracellular ATP levels ( P < 0.05), and inhibited cytochrome c release ( P < 0.05). AST exerts a significant cardioprotective effect against DOX-induced cardiotoxicity in rats, primarily by reducing ROS accumulation, restoring mitochondrial membrane potential, enhancing ATP production, inhibiting cytochrome c release, and activating the Nrf2-HO-1 signaling pathway.