Therapeutic potential of traditional Chinese medicine for hyperuricemia: mechanistic insights and clinical prospects.

Hyperuricemia (HUA) is a common metabolic disorder with rising global prevalence and is closely linked to gout, chronic kidney disease, and cardiovascular complications. Current Western drugs are limited by single-target mechanisms and adverse effects, whereas traditional Chinese medicine (TCM) is proposed to offer multi-component and multi-target therapeutic effects. This review critically synthesizes recent advances in TCM for HUA, focusing on how natural products modulate uric acid production (XOD/ADA), renal/intestinal excretion (URAT1, GLUT9, ABCG2, OATs), inflammation (NLRP3/NF-κB), and gut microbiota via the gut-kidney axis. We propose a four-tier hierarchical framework-purified metabolites, extracts, single botanical drugs, and formulas-that bridges molecular precision with systemic effects: metabolites serve as mechanistic probes, extracts and single botanical drugs achieve multi-component effects, and formulas enable network regulation. This framework helps deconstruct complex TCM interventions into testable, multi-target strategies. Beyond summarizing mechanisms, we critically examine methodological flaws in preclinical studies (acute models, prophylactic dosing, intraperitoneal injection) that limit translational validity, and highlight the pervasive gap between correlative findings (e.g., transporter expression, microbiota shifts) and causal evidence. We also address the under-appreciated safety profile of anti-HUA TCM, including potential organ toxicity and herb-drug interactions. By critically examining limitations, this review aims to provide a realistic, systems-level perspective to guide future mechanistic and translational research.