Dual mechanisms of a purified root extract of Paeonia lactiflora Pall. in regulating uric acid homeostasis: inhibition of hepatic synthesis and promotion of renal excretion in hyperuricemic rat models

Introduction: Hyperuricemia (HUA), characterized by persistently elevated serum uric acid (UA), represents a growing global public-health concern. Current urate-lowering medications are often associated with hepatotoxicity and nephrotoxicity, highlighting the urgent need for safer, food-derived alternatives. Methods: Pall. root extract was characterized by HPLC fingerprinting and evaluated in HK-2 human renal proximal tubular epithelial cells and a potassium oxonate/hypoxanthine-induced rat model of HUA. Results: , oral administration of PLE-2 (100, 200, and 400 mg/kg) dose-dependently reduced serum UA levels to ranges comparable with allopurinol, while attenuating renal injury (decreased creatinine and blood urea nitrogen, improved kidney histology). The mechanism involves dual regulation: suppression of hepatic UA production via inhibition of xanthine oxidase (XOD) and adenosine deaminase (ADA), and enhancement of renal UA excretion through downregulation of reabsorption transporters (URAT1, GLUT9) and upregulation of secretion transporters (OAT1, OAT3, ABCG2), confirmed by qPCR and Western blot. Molecular docking showed strong binding of paeoniflorin (the major metabolite in PLE-2) to these targets. Discussion: PLE-2 demonstrates potent dual action on UA synthesis and excretion with notable nephroprotective effects, positioning the purified fraction as a promising functional food metabolite for preventing and ameliorating HUA.