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

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.