State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.
J Ethnopharmacol. 2010 Apr 21;128(3):685-92. doi: 10.1016/j.jep.2010.02.012. Epub 2010 Feb 26.
Simiao pill is one of the most frequently prescription in traditional Chinese medicine to treat gout and hyperuricemia.
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.
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.
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.
These findings suggest that Simiao pill processes uricosuric and nephroprotective actions by regulating renal organic ion transporters in hyperuricemic animals.
四妙丸是中医治疗痛风和高尿酸血症最常用的处方之一。
本研究旨在探讨四妙丸对尿酸排泄和肾功能的影响,并研究肾脏有机离子转运体是否参与了氧嗪酸钾诱导的高尿酸血症小鼠模型。
将四妙丸水提取物以 507、1014 和 2028mg/kg 的剂量连续 7 天口服给予高尿酸血症和正常小鼠,别嘌醇(5mg/kg)作为阳性对照。测量高尿酸血症和正常小鼠给予四妙丸和别嘌醇后血清和尿液中尿酸和肌酐水平以及尿酸排泄分数(FEUA)。同时,通过半定量 RT-PCR 和 Western blot 方法分析肾脏中鼠尿酸转运体 1(mURAT1)、葡萄糖转运体 9(mGLUT9)和有机阴离子转运体 1(mOAT1)以及有机阳离子/肉碱转运体(mOCT1、mOCT2、mOCTN1 和 mOCTN2)的 mRNA 和蛋白水平。
四妙丸可显著降低高尿酸血症小鼠的血清尿酸水平,并呈剂量依赖性增加 FEUA。它还能有效逆转氧嗪酸钾诱导的肾脏 mURAT1、mGLUT9 和 mOAT1 mRNA 和蛋白水平的改变,从而增强小鼠的肾脏尿酸排泄。此外,四妙丸还降低了血清肌酐水平,增加了肾脏 mOCT1、mOCT2、mOCTN1 和 mOCTN2 的 mRNA 和蛋白水平,改善了该模型的肾功能。
这些发现表明,四妙丸通过调节高尿酸血症动物的肾脏有机离子转运体发挥其促尿酸排泄和肾保护作用。