Molecular mechanisms of Lycii Fructus (Goji berries) against xanthine dehydrogenase in hyperuricemia management: Integrating computational, metabolomic, and experimental approaches.

Lycii Fructus (LF), commonly known as Goji berries, has shown potential for managing hyperuricemia, though its underlying mechanisms remain poorly understood. This study employs a combination of network-based systems pharmacology, computer-aided drug discovery, untargeted metabolomics and experiments to explore the urate-lowering effects of LF. Molecular docking simulations of 3,760 LF compound-target interactions identified xanthine dehydrogenase (XDH) as a key target. Among the compounds, glycitein exhibited the highest binding affinity in molecular dynamics simulations. Metabolomics confirmed the presence of glycitein in LF particles, and it significantly reduced urate levels in hyperuricemia zebrafish models. Further in vitro assays and Cellular Thermal Shift Assays corroborated its inhibitory effect on xanthine oxidase. These findings suggest that glycitein may serve as a novel inhibitor of xanthine oxidase, with potential applications in nutraceuticals, functional foods, and drug development for hyperuricemia.