Yishen Qufeng formula mediates ferroptosis to improve renal fibrosis in unilateral ureteral obstruction rats

ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Qufeng Formula (YQF), an in-hospital preparation of the Jiangsu Provincial Hospital of Chinese Medicine, has been used clinically for the long-term treatment of kidney-related diseases. The formula was patented by the National Intellectual Property Administration of China. Preliminary studies have shown its renoprotective effects, though the underlying mechanisms remain unclear. AIM OF THE STUDY: To investigate the effects and mechanisms of YQF in improving renal fibrosis in unilateral ureteral obstruction (UUO) rats. MATERIALS AND METHODS: The chemical components of YQF were detected using Liquid Chromatography-Orbitrap-Mass Spectrometry. The UUO rat model was used to investigate the therapeutic effects and underlying mechanisms of YQF on renal fibrosis, and integrative multi-omics analysis was employed to elucidate the pharmacological mechanisms. Finally, in vivo and in vitro experiments were conducted for further validation. RESULTS: This is the first study where 68 active compounds were identified in YQF. YQF administration significantly improved renal function in UUO rats, reduced pathological kidney tissue damage, and decreased collagen deposition and iron accumulation. A comprehensive analysis revealed that YQF may inhibit renal fibrosis by improving ferroptosis through the p53/SLC7A11/GPX4 signaling pathway. CONCLUSIONS: These data establish YQF as a promising anti-fibrotic candidate, operating mechanistically via coordinated modulation of ferroptotic signaling cascades, redox homeostasis, and complementary pathological pathways to decelerate renal fibrogenesis.