Antihyperuricemic and nephroprotective effects of resveratrol and its analogues in hyperuricemic mice.

ABSTRACT

SCOPE Stilbenes, of which, resveratrol is a representative compound in foods and plants, possess a variety of bioactivities including antioxidation, anti-inflammation, chemoprevention, and cardioprotection. This study was conducted to evaluate the antihyperuricemic and nephroprotective effects of resveratrol and its analogues and explore the possible mechanisms. The structure-activity relationships were analyzed. METHODS AND RESULTS: Potassium oxonate-induced hyperuricemic mice were dosed by gavage with eight stilbenes. Uric acid, creatinine, and blood urea nitrogen (BUN) levels in serum and urine, clearance rate of creatinine and BUN, 24-h urate excretion, and fractional excretion of uric acid, uromodulin levels in urine and kidney were determined to evaluate renal urate handling and function. Renal protein levels of organic ion transporters were detected to elucidate the possible mechanisms. Resveratrol, trans-4-hydroxystilbene, pterostilbene, polydatin, and mulberroside A were found to have antihyperuricemic activities. These compounds together with trans-2-hydroxystilbene provided nephroprotection. Trans-3,4',5-trimethoxystilbene and cis-combretastatin A-4 had no effects. CONCLUSION: The uricosuric and nephroprotective actions of resveratrol and its analogues were mediated by regulating renal organic ion transporters in hyperuricemic mice, supporting their beneficial effects for the prevention of hyperuricemia. The number and position, methoxylation and glycosylation of hydroxyl groups in these trans-stilbenes were required for their effects.