Quercetin in metabolic diseases: mechanisms, therapeutics, and multidimensional frontiers

Background: Metabolic diseases represent a significant global public health concern, imposing substantial burdens on healthcare systems, economies, and patient quality of life. Current treatments have limitations, underscoring the need for safer alternatives. Quercetin, a natural flavonoid with favorable human tolerability, shows promise for metabolic disorder management. Purpose: This review critically evaluates the existing evidence on quercetin's role in metabolic disease management, summarizing its pharmacological advancements and clinical data in treating nine metabolic disorders: diabetes mellitus (DM), metabolic dysfunction-associated fatty liver disease (MAFLD), obesity, atherosclerosis, hyperuricemia, gouty arthritis, hyperlipidemia, osteoporosis, and polycystic ovary syndrome (PCOS). Methods: We systematically reviewed studies (2003-2025) from Web of Science, PubMed, Science Direct, and CNKI reporting quercetin's effects in metabolic diseases. Results: Quercetin exhibits multifaceted pharmacological activities, including anti-inflammatory, antioxidant, antiapoptotic, hypolipidemic, and hypoglycemic effects. This underpins its therapeutic potential against nine metabolic disorders. Furthermore, emerging nanodelivery systems have demonstrated enhanced bioavailability, stability, and overall efficacy of quercetin while mitigating its dose-dependent toxicity. Conclusion: Quercetin shows considerable promise in the intervention of metabolic diseases. However, current research lacks mechanistic depth, bioavailability enhancement data, and clinical validation Additionally, clinical studies validating its therapeutic efficacy remain scarce. Further mechanistic investigations and randomized controlled trials are imperative to elucidate quercetin's precise mechanisms and substantiate its clinical potential in metabolic disease management.