Identification of Inhibitory Activities of Dietary Flavonoids against URAT1, a Renal Urate Re-Absorber: In Vitro Screening and Fractional Approach Focused on Rooibos Leaves

Hyperuricemia, a lifestyle-related disease characterized by elevated serum urate levels, is the main risk factor for gout; therefore, the serum urate-lowering effects of human diets or dietary ingredients have attracted widespread interest. As Urate transporter 1 (URAT1) governs most urate reabsorption from primary urine into blood, URAT1 inhibition helps decrease serum urate levels by increasing the net renal urate excretion. In this study, we used a cell-based urate transport assay to investigate the URAT1-inhibitory effects of 162 extracts of plant materials consumed by humans. Among these, we focused on Aspalathus linearis, the source of rooibos tea, to explore its active ingredients. Using liquid–liquid extraction with subsequent column chromatography, as well as spectrometric analyses for chemical characterization, we identified quercetin as a URAT1 inhibitor. We also investigated the URAT1-inhibitory activities of 23 dietary ingredients including nine flavanols, two flavanonols, two flavones, two isoflavonoids, eight chalcones, and a coumarin. Among the tested authentic chemicals, fisetin and quercetin showed the strongest and second-strongest URAT1-inhibitory activities, with IC(50) values of 7.5 and 12.6 μM, respectively. Although these effects of phytochemicals should be investigated further in human studies, our findings may provide new clues for using nutraceuticals to promote health.