Anti-hyperuricemic effect of taxifolin in cultured hepatocytes and model mice

Abstract

Hyperuricemia is recognized as an important risk factor for gout. High dietary intake of purine-rich foods such as meats and sea foods increases uric acid (UA) levels in the blood. Taxifolin present in Siberian larch and strawberries has been reported to possess health promoting activities including anti-oxidant effect. In this study, we examined anti-hyperuricemic effect of taxifolin in both cultured hepatocytes and hyperuricemic model mice. In cultured AML12 hepatocytes, taxifolin significantly suppressed UA production dose- and time-dependently. In mice with hyperuricemia induced by concurrent administration of guanosine-5'-monophosphate and inosine-5'-monophosphate, oral administration of taxifolin suppressed the increases in plasma and liver UA levels. In addition, it also suppressed hepatic xanthine oxidase (XO) activity. Thus, anti-hyperuricemic effect of taxifolin could be explained, at least partly, by suppressing UA production via inhibition of XO activity in the liver. These results suggest that taxifolin possesses a potent hypouricemic effect and it could be a potential candidate for an anti-hyperuricemic phytochemical.

Keywords: AML12 hepatocyte; Hyperuricemia; Taxifolin; Uric acid.

Fig. 1

Structure of taxifolin (dihydroquercetin)

Fig. 2

Effects of taxifolin and allopurinol on UA production in AML12 hepatocytes. AML12 cells were treated with 0.1, 1 and 10 µM allopurinol for 2 h (a) or with 25, 50 and 100 µM taxifolin for 2 h (b) or 4 h (c) in balanced salt solution containing guanosine + inosine (100 µM each). d indicates relative UA production by AML12 cells treated with taxifolin for 2 or 4 h, data being expressed as percentage of the 0 µM taxifolin. Each value represents mean ± SEM for six wells (duplicate measurements per well). Values not sharing a common letter are significantly different at P < 0.05 (Tukey’s test). *P < 0.05 compared with the 2 h-treated group with the corresponding concentrations by unpaired t test

Fig. 3

Effects of taxifolin and allopurinol on plasma uric acid levels in hyperuricemic mice. The mice were orally administered with taxifolin and allopurinol at the different doses indicated. The mice were then intraperitoneally injected with both GMP and IMP (300 mg each/kg body weight) to induce hyperuricemia. Normal control and model control groups were treated with vehicles instead of test samples and nucleotides. Each value represents mean ± SEM for eight mice (duplicate measurements per mouse). *Significantly different from the model control group at P < 0.05 (Dunnett’s test)

Fig. 4

Effects of taxifolin and allopurinol on liver uric acid levels (a) and xanthine oxidase activity (b) in hyperuricemic mice. The mice were orally administered with taxifolin and allopurinol at the different doses indicated. The mice were then intraperitoneally injected with both GMP and IMP (300 mg each/kg body weight) to induce hyperuricemia. Normal control and model control groups were treated with vehicles instead of test samples and nucleotides. Each value represents mean ± SEM for eight mice (duplicate measurements per mouse). *Significantly different from the model control groups at P < 0.05 (Dunnett’s test)