Actions of Inonotus obliquus against Hyperuricemia through XOD and Bioactives Screened by Molecular Modeling

Inonotus obliquus is an edible mushroom and also a remedy against various diseases, especially metabolic syndrome. In this paper we report the actions of an ethanol extract of I. obliquus (IOE) against hyperuricemia in hyperuricemic mice, and the screen of bioactives. The extract (IOE) was prepared by extracting I. obliquus at 65 degrees C with ethanol, and characterized by HPLC. IOE at low, middle, and high doses reduced serum uric acid (SUA) of hyperuricemic mice (353 mol/L) to 215, 174, and 152 mol/L (p < 0.01), respectively, showing similar hypouricemic effectiveness to the positive controls. IOE showed a non-toxic impact on kidney and liver functions. Of note, IOE suppressed xanthine oxidase (XOD) activity in serum and liver, and also down-regulated renal uric acid transporter 1 (URAT1). Four compounds hit highly against XOD in molecular docking. Overall, the four compounds all occupied the active tunnel, which may inhibit the substrate from entering. The IC50 of betulin was assayed at 121.10 +/- 4.57 M, which was near to that of allopurinol (148.10 +/- 5.27 M). Betulin may be one of the anti-hyperuricemia bioactives in I. obliquus.