Astragaloside IV Alleviates Cisplatin Chemotherapy‐Induced Nephrotoxicity via Modulation of Nrf2/HO‐1/NF‐κB Pathway and Reversal of EMT Process

ABSTRACT High incidence of nephrotoxicity poses a significant hurdle to the clinical utility of cisplatin (CDDP), which profoundly impacts the efficacy of chemotherapy. Astragaloside IV (AS‐IV) is a characteristic saponin component of Astragalus membranaceus , known for its antioxidant and anti‐inflammatory properties. However, the precise role of AS‐IV in the context of CDDP chemotherapy remains elusive. Herein, we unveil AS‐IV's capability to alleviate CDDP‐induced nephrotoxicity in Lewis lung carcinoma mice and renal tubular epithelial cells (RTECs). This is achieved by upregulating antioxidant enzymes, activating Nrf2/HO‐1 pathway, while concurrently suppressing release of pro‐inflammatory cytokines and inhibiting p‐NF‐κB(p65) expression. Furthermore, our research reveals the anti‐fibrosis ability of AS‐IV on RTECs induced by inflammatory mediators TNF‐α and TGF‐β1 through reversal of the epithelial‐mesenchymal transformation (EMT) process. These findings not only suggest the viable potential of AS‐IV in combination with CDDP to alleviate nephrotoxicity, but also underscore its medicinal promise in enhancing chemotherapy effectiveness.