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Ethnopharmacological Relevance: Simiao pill is one of the most frequently prescription in traditional Chinese medicine to treat gout and hyperuricemia., Aim of the Study: We investigated the effects of Simiao pill on urate excretion and renal function and examined whether renal organic ion transporters are involved in potassium oxonate-induced hyperuricemic mice., Materials and Methods: Water extract of Simiao pill at 507, 1014 and 2028mg/kg was orally administered to hyperuricemic and normal mice for 7 days, and allopurinol (5mg/kg) was given as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic and normal mice treated with Simiao pill and allopurinol. Simultaneously, the mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9) and organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in the kidney were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively., Results: Simiao pill significantly reduced serum uric acid levels and increased FEUA dose-dependently in hyperuricemic mice. And it effectively reversed oxonate-induced alterations in renal mURAT1, mGLUT9 and mOAT1 mRNA and protein levels, resulting in the enhancement of renal urate excretion in mice. Moreover, Simiao pill decreased serum creatinine levels, as well as increased renal mOCT1, mOCT2, mOCTN1 and mOCTN2 mRNA and protein levels, leading to improve renal dysfunction in this model., Conclusion: These findings suggest that Simiao pill processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic animals., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Renal organic ion transporters and uromodulin (UMOD) play the important roles in renal urate excretion and function. Hyperuricemia is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin in diets exerts the hypouricemic and nephroprotective effects. Purposes: To evaluate the effects of quercetin on renal organic ion transporters and UMOD in hyperuricemic mice. Methods: Kun-Ming mice were divided into normal and hyperuricemic groups receiving water, 25, 50 and 100 mg/kg quercetin, 5 mg/kg allopurinol, respectively. Hyperuricemic mice were orally gavaged with 250 mg/kg oxonate daily for 1 week. Quercetin and allopurinol were orally gavaged on the day when oxonate or water was given 1 h later. After 1 week, serum uric acid, creatinine and blood urea nitrogen concentrations, excretion of urate and creatinine, and fractional excretion of uric acid were measured. The mRNA and protein levels of renal urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1, mOCT2, mOCTN1 and mOCTN2) in mice were analyzed. Simultaneously, UMOD levels in serum, urine and kidney, as well as renal UMOD mRNA expression were detected. Results: Quercetin significantly restored oxonate-induced abnormalities of these biochemical indexes compared with normal vehicle group. Furthermore, it remarkably prevented expression changes of renal organic ion transporters and UMOD, and UMOD level alteration in hyperuricemic mice. Conclusions: These results suggest that quercetin has the uricosuric and nephroprotective actions mediated by regulating the expression levels of renal organic ion transporters and UMOD. [ABSTRACT FROM AUTHOR]