Medicinal plants have long been used to manage hyperuricemia (HUA) and gout, with flavonoids identified as key bioactive components. However, the therapeutic effects of flavonoids on HUA remain inadequately characterized. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of flavonoids on serum uric acid (UA) and xanthine oxidase (XOD) activity in animal models. A comprehensive literature search of the PubMed and Web of Science databases (January 2007–December 2024) identified 21 eligible studies involving 550 male mice. A random-effects meta-analysis revealed that flavonoid administration significantly reduced serum UA (standardized mean difference SMD = –2.22, 95% confidence interval (CI): –2.80 to –1.64; p < 0.001) and XOD activity (SMD = –1.79, 95% CI: –2.50 to –1.08; p < 0.001). Subgroup analyses indicated that chalcones, flavonols, and flavones exerted the most pronounced hypouricemic effects. Molecular docking of 28 flavonoids to XOD yielded binding affinities ranging from –8.4 to –10.9 kcal/mol, with molecular dynamics simulations confirming stable ligand–enzyme complexes; flavones exhibited the highest stability. Collectively, these data provide robust preclinical evidence that flavonoids ameliorate hyperuricemia via dual mechanisms of UA reduction and XOD inhibition, and support the further clinical development of flavonoids as potential natural agents for managing HUA.
Zhao et al. (2026) studied this question.