Abstract:This study investigated the ameliorative effect and underlying mechanism of Dioscorea opposita Thunb. extract （DOT） on hyperuricemia （HUA）. The anti-HUA effect of DOT was examined using dietinduced HUA animal models and monosodium urate （MSU）-stimulated human renal tubular epithelial cell models. Furthermore，network pharmacology combined with experimental validation was used to elucidate the potential mechanism of DOT. In both in vivo and in vitro HUA models，DOT suppressed the release of proinflammatory cytokines and promoted the secretion of anti-inflammatory factors. DOT reduced serum uric acid and creatinine levels. Histological analysis of renal tissue sections revealed that DOT alleviated inflammatory infiltration in renal tubules and suppressed MSU crystal deposition in HUA mice. Network pharmacology and experimental validation indicated that DOT inhibited reactive oxygen species and malondialdehyde generation while promoting glutathione activity，thereby mitigating oxidative stress. Molecular docking and Western blot analysis demonstrated that DOT suppressed oxidative stress via the Nrf2/HO-1 pathway，thereby alleviating MSU-induced renal injury.