Abstract
The objectives of the present study were to demonstrate the antihyperuricemic effect of triphala, a formulation of traditional Ayurvedic medicine, in potassium oxonate-induced hyperuricemic mice in vivo, and to examine its inhibitor effects on xanthine oxidase (XOD), inflammatory mediators and DPPH radicals in vitro. The water extract of triphala was determined to contain the total phenolics and total flavonoids of 317.6 ± 9.2 mg GAE/g and 7.73 ± 0.26 mg QE/g, respectively. Oral administrations of triphala significantly reduced the plasma uric acid levels of potassium oxonate-induced hyperuricemic mice at doses of 1,000 and 1,500 mg/kg, as compared with control (p<0.05). Moreover, both doses of triphala treatments markedly inhibited the formation of uric acid due to inhibition of XOD activity in liver homogenates extracted from the hyperuricemic mice by about 70-80%. Lineweaver-Burk analysis of enzyme-kinetic data showed that triphala exhibited non-competitive inhibition on XOD activity in vitro with an inhibitory constant (Ki) of 590 μg/mL. Furthermore, triphala significantly suppressed the mRNA expressions of COX-II, TNF-α and iNOS in LPS-stimulated RAW 264.7 cells, as compared with control (p <0.05), and decreased the expression of TGF-β. IC50 values for inhibition of DPPH radical formation was calculated to be 21.9 ± 2.50 μg/mL. Antioxidant activities of triphala were determined to be 0.81 ± 0.07 g TEAC/g and 6.78 ± 0.29 mmol/100g, respectively, as assessed by ABTS and FRAP assays. In conclusion, this study provided in vivo and in vitro mechanistic evidence for the antihyperuricemic, antioxidative and anti-inflammatory effects of triphala for the first time, rationalizing its therapeutic usage for the treatment of hyperuricemia of gout.