Abstract
Acute kidney injury (AKI) is a common side effect of the chemotherapy agent cisplatin, and ferroptosis serves as the primary mechanism underlying cell death in renal tubular epithelium in such cases. Salvianolic acid B (SAB), a compound derived from Salvia miltiorrhiza, has demonstrated promising anti-inflammatory and antioxidant properties. However, its impact on ferroptosis in the context of AKI remains to be fully explored. In this study, we utilized cisplatin-induced and folic acid-induced AKI models to investigate the protective mechanisms of SAB on renal tissue and tubular epithelial cell injury. The impact of SAB on renal cell ferroptosis was thoroughly examined and confirmed in both AKI models. To predict the potential mechanism through which SAB regulates ferroptosis, we employed an online target prediction database and subsequently verified the specific target proteins involved. Furthermore, we used drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA) and molecular docking techniques to assess the binding capacity of SAB to the target protein. Our results reveal that SAB alleviated cisplatin- and folic acid-induced renal dysfunction in vivo and improved cisplatin-induced HK-2 cell injury. Mechanistically, SAB targeted and bound to PRDX5, enhancing its redox activity, which in turn potentiated the inhibitory effect of SLC7A11 and GPX4 on cisplatin-induced ferroptosis. Silencing PRDX5 in HK-2 cells could partially abrogate the protective effect of SAB. These results provide strong evidence for the potential of SAB in the treatment of AKI.