Apple polyphenols alleviate hyperuricemia by inhibiting xanthine oxidase and promoting uric acid excretion

Hyperuricemia, a metabolic disorder caused by excessive uric acid accumulation, is a major risk factor for gout and related kidney damage. Current pharmacological treatments often have side effects, emphasizing the need for safer alternatives. This study investigated the preventive and therapeutic potential of apple polyphenols (AP) in hyperuricemia management, as well as the underlying mechanisms. A cross-sectional analysis of 15,121 Chinese undergraduates revealed that apple consumption was inversely associated with hyperuricemia risk (OR = 0.86; 95 % CI: 0.73–0.99; P = 0.028). A hyperuricemia mouse model was established by potassium oxonate and adenine for 21 days, and AP treatment significantly reduced serum uric acid levels by inhibiting both the activity and expression of xanthine oxidase, and by downregulating renal uric acid transporters URAT1 and GLUT9. Histopathological analysis indicated that AP alleviated kidney and liver damage caused by hyperuricemia. These findings highlight the dual regulatory effect of AP on uric acid synthesis and excretion, providing new insights into its potential as a natural dietary intervention for hyperuricemia management.