Abstract

Ethnopharmacological relevance Yupingfeng San (YPFS), a classic tonic formula in Traditional Chinese Medicine (TCM), has been extensively applied clinically for centuries. Originating from Jiuyuan Fang , its earliest extant record is Danxi Xinfa . YPFS is composed of Huangqi ( Astragalus membranaceus Bunge), Baizhu ( Atractylodes rubra Dekker), and Fangfeng ( Saposhnikovia divaricata (Turcz.) Schischk). Due to its traditional efficacy of " replenishing qi and consolidating the exterior," YPFS is commonly prescribed for allergic rhinitis, nephrotic syndrome, and chronic nephritis. Recent studies have confirmed that YPFS protects renal function and alleviates renal fibrosis in mice with diabetic nephropathy, while simultaneously improving lung function and reducing pulmonary fibrosis in bleomycin-induced rats. Taken together, these results suggest YPFS possesses substantial potential for mitigating organ fibrosis. Purpose This study investigated the renoprotective efficacy and underlying mechanism of YPFS extract in a cisplatin-induced mouse model of renal interstitial fibrosis. Using an integrated in vivo and in vitro approach, we sought to validate the therapeutic potential of this traditional formula against chemotherapy-induced nephrotoxicity. Methods The chemical components of YPFS extract were analyzed using UPLC-Q-TOF -MS. For the in vivo study, male BALB/c mice received YPFS extract (1, 1.95, or 3 g/kg) by oral administration once daily for 7 days after a single injection of cisplatin (20 mg/kg, i.p.). Renal function was assessed by measuring serum creatinine, plasma BUN, fasting blood glucose, and the urine protein-to-creatinine ratio. Kidney tissues were examined using H&E and Masson's trichrome staining for histopathological analysis, and the expression of fibrosis markers (α-SMA, collagen I, fibronectin) was measured by immunohistochemistry and western blotting. For the in vitro study, MPC-5 podocytes were treated with high glucose (25 mM) for 48 h t