Tiliroside Suppresses Uric Acid Production in Hepatocytes and Attenuates Purine-Induced Hyperuricemia in Male ICR Mice

Tiliroside (kaempferol-3-O-(6''-p-coumaroyl)-glucoside), a flavonoid glycoside found in rose hips and berries, has been reported to possess various bioactivities. This study aimed to evaluate its antihyperuricemic potential by assessing direct xanthine oxidase (XO) inhibitory activity, suppression of uric acid (UA) production in AML12 hepatocytes, and efficacy in male ICR mice with purine nucleotide-induced hyperuricemia. XO inhibition was evaluated using a UV absorbance-based assay, and UA production was measured in hepatocytes stimulated with UA precursors. Mice were orally administered tiliroside for three days prior to purine nucleotide injection. Although tiliroside exhibited weak XO inhibition (IC₅₀ > 100 µM), it significantly suppressed UA production in hepatocytes in a concentration-dependent manner. In hyperuricemic mice, tiliroside (300 mg/kg) lowered plasma and hepatic UA levels by approximately 30% and 55%, respectively (<i>p</i> < 0.05). Hepatic XO activity was significantly decreased, while XO protein expression remained unchanged. Furthermore, mRNA levels of urate transporter 1 (URAT1) were significantly decreased in the kidney of tiliroside-treated hyperuricemic mice. These findings suggest that tiliroside exerts antihyperuricemic effects by suppressing UA production in the liver and modulating renal UA reabsorption. Tiliroside may serve as a beneficial dietary compound with bioactivity for the prevention and management of hyperuricemia and gout.