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Astragaloside IV (ASIV) is the main active component of Astragalus, and can ameliorate cardiomyocyte hypertrophy, apoptosis and fibrosis. In this experiment, we studied how ASIV reduces the cardiotoxicity caused by adriamycin and protects the heart. To this end, rats were randomly divided into the control, ADR, ADR + ASIV and ASIV groups (n = 6). Echocardiography was used to observe cardiac function, HE staining was used to observe myocardial injury, TUNEL staining was used to observe myocardial cell apoptosis, and immunofluorescence and Western blotting was used to observe relevant proteins expression. Experiments have shown that adriamycin can damage heart function in rats, and increase the cell apoptosis index, autophagy level and oxidative stress level. Further results showed that ADR can inhibit the PI3K/Akt pathway. ASIV treatment can significantly improve the cardiac function of rats treated with ADR and regulate autophagy, oxidative stress and apoptosis. Our findings indicate that ASIV may reduce the heart damage caused by adriamycin by activating the PI3K/Akt pathway.

Adriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstrated that ASIV significantly ameliorated kidney injury, improved renal dysfunction, reduced oxidative stress, alleviated iron accumulation, and inhibited the induction of ferroptosis by ADR. ASIV also rescued the intracellular levels of nuclear factor-erythroid-2-related factor 2 (Nrf2) and promoted nuclear translocation of Nrf2. These protective effects of ASIV on renal injury might be attained through the ASIV-induced activation of the Pi3K/Akt signaling pathway. In vitro, the treatment of the HK-2 cells with fer-1 or deferoxamine mesylate obviously improved cell viability during Adriamycin administration. On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent. Moreover, ASIV lowered the expression of transferrin receptor 1 and divalent metal transporter 1 while enhancing the expression of ferropotin 1 and glutathione peroxidase 4 in ADR administrated cells, the effects of which were akin to those of deferoxamine mesylate. Furthermore, ASIV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.