Emerging therapeutic role of cinnamic acid derivatives in hyperuricemia and gout: mechanistic, translational, and pharmacological perspectives.

Hyperuricemia and gout are increasingly common metabolic and inflammatory disorders characterized by excessive accumulation of uric acid, impaired urate excretion, oxidative stress, and monosodium urate crystal inflammation. Although currently available therapies such as xanthine oxidase inhibitors and uricosuric agents effectively reduce serum levels of uric acid, their long-term clinical use is often associated with adverse reactions, limited tolerability, and incomplete disease management. As a result, there is increasing interest in identifying natural compounds that may serve as a potential preclinical lead for the development of more targeted urate-lowering strategies. Cinnamic acid derivatives, including p-coumaric acid, caffeic acid, ferulic acid, sinapic acid, chlorogenic acid, and synthetic analogs such as 4-nitrocinnamic acid, have shown promising anti-hyperuricemic and anti-gout activities in experimental studies. These compounds have pharmacological effects through several mechanisms, including the inhibition of xanthine oxidase; modulation of urate transporters such as URAT1, GLUT9, and ABCG2; suppression of inflammatory pathways including NF-κB and NLRP3 inflammasome signalling; antioxidant activity; and protection against renal injuries induced by uric acid. This review summarizes the molecular mechanisms, pharmacological evidence, and structure-activity relationships of selected cinnamic acid derivatives related to hyperuricemia and gout management. In addition, it discusses translational challenges associated with bioavailability, pharmacokinetics, toxicity evaluation, and clinical validation. Collectively, cinnamic acid derivatives represent promising pre-clinical leads that warrant further preclinical and clinical investigations to develop safer and more effective therapies against hyperuricemia and gout.