Effect and Mechanism of Flavonoids from Wheat Seedlings on Alleviating Hyperuricemia by Targeted Inhibition of Xanthine Oxidase

Abstract Wheat seedlings are a flavonoid-rich cereal by-product with potential for hyperuricemia management. This study evaluated the hypouricemic activity of wheat seedling extracts and elucidated the mechanism. Wheat seedling ethanol extract (WE) showed markedly higher total flavonoid content than water extract (WW), corresponding to superior in vitro xanthine oxidase (XO) inhibition. In hyperuricemic mice, WE (250 mg/kg) reduced serum uric acid by 41% and ameliorated renal and hepatic injury and exhibited no observable toxicity. Purification of WE using AB-8 macroporous resin revealed that the WE eluate of the 40% ethanol fraction (WSEE-40%) with substantially enhanced XO inhibition, characterized as mixed-type reversible inhibition. Metabolomic analysis identified 258 flavonoids; among these, 188 were enriched in WSEE-40%. Mechanistically, the representative flavonoid saponarin bound XO at a single site via static quenching with hydrophobic interactions as the dominant driving force. These findings establish wheat seedling flavonoids as effective XO inhibitors and support valorization of this cereal by-product for functional food applications in hyperuricemia management.