Bioactive Components, Untargeted Metabolomics and Bioinformatics of Chaenomeles speciosa Fruit on Uric Acid-Lowering Activity Assessment

(Sweet) Nakai (CF), a traditional food in East Asia and a recent addition to clinical dietary recommendations, has demonstrated potential for managing hyperuricemia. However, its bioactive components and therapeutic mechanisms remain largely unexplored. In this study, we used an integrative approach incorporating serum pharmacochemistry, metabolomics, bioinformatics, molecular docking, and in vitro/vivo validation to investigate CF's effects and mechanisms in hyperuricemia. In hyperuricemic mice, CF significantly reduced serum uric acid, creatinine, and blood urea nitrogen (BUN) levels, improved kidney histopathology, and restored redox balance by increasing antioxidant enzyme activities (SOD and GSH-Px) while lowering malondialdehyde (MDA) levels. Metabolomic analysis revealed that CF modulated pathways associated with oxidative stress, including purine metabolism, arachidonic acid metabolism, and α-linolenic acid metabolism, to reverse hyperuricemia-associated metabolic perturbations. Correlation analysis between differential metabolites and serum-absorbed constituents identified androsin, cynaroside, and salicin as potential bioactive compounds. These compounds showed high predicted binding affinities to COX-1, PGE2, and XOD in molecular docking, and these interactions were validated by in vitro assays, where the compounds effectively suppressed inflammatory cytokine production and inhibited XOD activity. Overall, CF exerts anti-hyperuricemic and renoprotective effects through coordinated regulation of purine metabolism, inflammation, and oxidative stress, supporting its potential as a functional food or complementary therapy for hyperuricemia-related conditions.