Therapeutic potential and molecular mechanisms of natural compounds for managing hyperuricemia

Hyperuricemia (HUA), marked by elevated serum uric acid (SUA) levels, is a prevalent metabolic disorder associated with gout and chronic conditions such as cardiovascular diseases and malignancies. Synthetic drugs, including xanthine oxidase inhibitors and uricosuric agents, effectively lower SUA but often lead to side effects such as gastrointestinal distress, allergic reactions, and renal toxicity. In contrast, natural substances like flavonoids and polyphenols have demonstrated the ability to reduce UA levels and alleviate inflammation with fewer adverse effects, driving interest in their therapeutic potential. This review comprehensively explores HUA treatment strategies, examining the mechanisms, efficacy, and safety of synthetic drugs and natural substances. Recent advancements in pharmacological therapies, including novel drug delivery systems, are highlighted alongside bioactive compounds from plants, fungi, and marine organisms. In addition, this review innovatively summarizes recent studies on the synergistic effects between traditional drugs and natural substances within novel therapeutic frameworks, confirming that such synergism can reduce drug toxicity while maintaining targeted blood uric acid control. This discovery has opened new avenues for optimizing existing treatment protocols, providing fresh directions for enhancing therapeutic efficacy and minimizing adverse effects. It particularly highlights how pharmaceutical technologies such as metal complexation can address the low bioavailability issues of natural products. This integrative perspective underscores the importance of combining modern pharmacological advancements with natural substances, paving the way for the development of safer and more effective treatments for HUA.