Xanthine oxidase inhibitory and anti-hyperuricemic properties of sulfonate derivatives of naringenin.

Xanthine oxidase (XO) facilitates oxidation of hypoxanthine to xanthine and then to uric acid, potentially leading to hyperuricemia when production of excessive uric acid. In the present study, naringenin-3'-sulfonate sodium and naringenin-3',6-disulfonate sodium were synthesized by chemical modification of naringenin, and evaluated for XO inhibitory activities in vitro. The results indicated that naringenin-3'-sulfonate sodium exhibited significantly inhibitory activities compared to naringenin and naringenin-3',6-disulfonate sodium. Further inhibitory kinetics, fluorescence spectra, circular dichroism spectra and molecular docking analysis revealed that as a reversible competitive inhibitor, naringenin-3'-sulfonate sodium could bind to the active site of XO and induce conformational changes through hydrogen bond, hydrophobic forces, π-π stacking and electrostatic interaction. Furthermore, naringenin-3'-sulfonate sodium was effective in reducing serum uric acid levels in hyperuricemic mice, which was found to be associated with the inhibition of serum XO activity. Additionally, naringenin-3'-sulfonate sodium exhibited potential in ameliorating renal damage as evidenced by serum creatinine analysis and histopathological examination of renal tissues. These findings provide compelling evidence for the promising role of naringenin-3'-sulfonate sodium as a preventive or therapeutic agent against hyperuricemia.