The dual actions of Sanmiao wan as a hypouricemic agent: Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice
The dual actions of Sanmiao wan as a hypouricemic agent: Down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice
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DOI：
10.1016/j.jep.2009.12.035
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发表时间：
2010-03-02
影响因子：
5.4
通讯作者：
Kong, Ling-Dong
中科院分区：
文献类型：
--
作者：
Wang, Xing;Wang, Cai-Ping;Kong, Ling-Dong
民族药理学相关性：三妙丸（SMW）是一种治疗痛风和高尿酸血症的中药制剂，本研究旨在探讨SMW对高尿酸血症小鼠的降尿酸作用及其可能机制。高尿酸血症小鼠和正常小鼠经口给予489、978和1956 mg/kg的SMW，并以标准药物别嘌呤醇（2.5 mg/kg）作为阳性对照。测定SMW对小鼠血清、尿液和肝脏尿酸水平、血清肌酐水平和肝脏黄嘌呤氧化酶（XOD）活性的影响。结果：SMW能显著降低高尿酸血症小鼠血清和肝脏尿酸水平，抑制高尿酸血症小鼠肝脏XOD活性、mRNA和蛋白水平。SMW能有效下调高尿酸血症小鼠肾脏mURAT 1 mRNA和蛋白水平。它还能逆转氧磷酸钠诱导的小鼠血清肌酸酐水平升高。结论：SMW对高尿酸血症小鼠具有双重降尿酸作用，即通过抑制肝脏XOD减少尿酸生成，下调肾脏mURAT 1减少尿酸重吸收，促进尿酸排泄。皇冠版权所有（C）2009由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Ethnopharmacological relevance: Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.Aim of the study: The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.Materials and methods: SMW at 489,978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5 mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal mate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.Results: SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.Conclusion: These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance mate excretion in hyperuricemic mice. Crown Copyright (C) 2009 Published by Elsevier Ireland Ltd. All rights reserved.