Comprehensive Evaluation of the Antihyperuricemic Effect of Red Kidney Bean Anthocyanins and Molecular Screening of the Lead Candidate

This study aimed to investigate the effects of red kidney bean (Phaseolus vulgaris L.) anthocyanins (RKBA) on alleviating hyperuricemia (HUA) and screen the lead candidate. First, RKBA effectively inhibited XOD in vitro. Then, in vivo results showed that RKBA significantly reduced serum uric acid (UA) levels, protected kidney function, and alleviated inflammation and tissue damage. Mechanistically, RKBA down-regulated XOD, ADA, and 5′-NT while modulating urate transporters URAT1, GLUT9, and OAT3, thereby rebalancing UA metabolism. Additionally, it reshaped the gut microbiome (particularly enriching Ligilactobacillus and Dubosiella) and elevated short-chain fatty acids. Subsequently, the UPLC–ESI-MS/MS-based anthocyanin-targeted omics identified and quantified 42 anthocyanins. 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 XOD. Pelargonidin-3,5-diglucoside has not been reported as an antihyperuricemic nutraceutical before; hence, this study lays a foundation for future in vivo validation.