Comparison of the anti‐hyperuricemia effects of several cinnamic acid derivatives

Abstract BACKGROUND Cinnamic acid derivatives, such as p ‐coumaric acid, caffeic acid, ferulic acid, and chlorogenic acid, exhibit uric acid‐lowering effects through the inhibition of xanthine oxidase (XOD). While the clinically used XOD inhibitor allopurinol is associated with significant side effects, these natural polyphenolic compounds exhibit comparable efficacy with improved safety. RESULTS In hyperuricemic mouse models and in vitro assays, these polyphenolic compounds effectively reduced serum uric acid levels through XOD inhibition. Notably, ferulic acid and caffeic acids exhibited superior potency and reduced hepatic and renal toxicity in comparison to p ‐coumaric acid, with molecular docking studies suggesting competitive binding at the active site of XOD. Additionally, chlorogenic acid demonstrated significant activity. CONCLUSION These findings underscore the potential of naturally derived polyphenolics as promising candidates for the management of hyperuricemia, providing a safer alternative to conventional therapies. © 2025 Society of Chemical Industry.