In vitro xanthine oxidase inhibitory and in vivo anti-hyperuricemic properties of sodium kaempferol-3′-sulfonate

Xanthine oxidase (XO), a key enzyme in purine catabolism, catalyzes the oxidation of xanthine to uric acid in the body, but overproduction of uric acid may lead to hyperuricemia. This study aims to investigate in vitro XO inhibitory and in vivo anti-hyperuricemic properties of sodium kaempferol-3′-sulfonate (KS). The kinetic analysis indicates that KS is a reversible competitive inhibitor and has significant inhibitory effects on XO activity with an IC50 value of 0.338 μM. Fluorescence spectra suggested that KS could cause fluorescence quenching and conformational changes of XO due to the formation of a KS-XO complex. Molecular docking studies demonstrated that KS interacted with several amino acid residues of XO by the π-π stacking, hydrogen bonds, and hydrophobic interactions. The inhibitory mechanism of KS on XO activity might be the insertion of KS into the active site of XO to prevent the entrance of the substrate xanthine and induce conformational changes of XO. The results carried out in hyperuricemic mice showed that KS reduced serum XO activity, serum uric acid (UA), creatinine (CRE), and urea nitrogen (BUN) levels, as well as alleviating renal histopathological injury. These findings suggest that KS may be a new potent XO inhibitor against hyperuricemia-related diseases. •Sodium kaempferol-3′-sulfonate (KS) exhibited significant inhibitory effects on XO.•KS inhibited XO activity in a reversible competitive manner.•KS could bind the active site of XO to form a KS-XO complex.•KS had anti-hyperuricemic and nephroprotective effects in hyperuricemic mice.