Comprehensive Evaluation of Anti-hyperuricemic Effect of Red Kidney Bean Anthocyanins and Molecular Screening of the Lead Candidate

Hyperuricemia (HUA) has emerged as an increasingly prevalent metabolic disorder worldwide. This study aimed to investigate the effects of red kidney bean (Phaseolus vulgaris L.) anthocyanins (RKBA) on alleviating HUA and screen the lead candidate. RKBA effectively inhibited XOD in vitro. In vivo results showed that RKBA significantly reduced serum uric acid levels (p < 0.05), protected kidney function, alleviated inflammation and tissue damage in vivo. Mechanistically, RKBA down-regulated xanthine oxidase, adenosine deaminase and 5′-nucleotidase while modulating urate transporters URAT1, GLUT9 and OAT3, thereby rebalancing uric-acid metabolism. Additionally, it reshaped the gut microbiome (particularly increasing Ligilactobacillus and Dubosiella), and elevated short-chain fatty acids. Subsequently, UPLC-ESI-MS/MS-based anthocyanin-targeted omics identified and quantified 42 anthocyanins, which is the most comprehensive RKBA profiling to date. Ultimately, integrating molecular docking and dynamics simulation, pelargonidin-3,5-diglucoside was selected as the lead candidate owing to its high abundance and strong affinity for xanthine oxidase, which was further confirmed by in vitro experiment. Pelargonidin-3,5-diglucoside has not been reported as an anti-hyperuricemic nutraceutical before, hence this study lays a foundation for future in vivo validation.