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 (<i>Phaseolus vulgaris</i> L.) anthocyanins (RKBA) on alleviating hyperuricemia (HUA) and screen the lead candidate. First, RKBA effectively inhibited XOD <i>in vitro</i>. Then, <i>in vivo</i> 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 <i>Ligilactobacillus</i> and <i>Dubosiella</i>) 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 <i>in vivo</i> validation.