Distinctions between terrestrial- and marine-derived anti-hyperuricemia bioactive substances: types, mechanisms and structure-activity relationships

Abstract Hyperuricemia (HUA) has become a prevalent metabolic disorder worldwide, attracting widespread attention from society. Existing uric acid (UA)-lowering medicines have substantial side effects in clinical practice, whilst long-term dietary therapies may result in nutritional imbalance. Therefore, how to efficiently extract and develop high-performance substances with UA-lowering activity from nature has gained growing research attention. This review examines the types, mechanisms of action, and structure-activity relationships of compounds with UA-lowering activity from terrestrial and marine sources. Terrestrial compounds primarily exert their effects by inhibiting xanthine oxidase (XOD) and regulating UA transporters. In contrast, marine-derived bioactive compounds generally display greater structural diversity and interact with a broader range of functional targets, particularly those related to gut microbiota regulation, inflammation, and UA transport. Emerging preclinical evidence also suggests their potential for multi-target regulation of metabolic syndrome-related disorders, although further clinical validation is required. Comparative analysis reveals that many phenolic acids and terpenoids from terrestrial and marine sources possess similar structural characteristics, such as conjugated planar frameworks as well as hydroxyl and methoxy functional groups, which enhance their binding affinity toward XOD and thereby contribute to their UA-lowering activity. The above finding not only indicates that marine organisms may be an important source of anti-hyperuricemia substances but also provides references and ideas for the screening, development, and design of novel UA-lowering components for future research.