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桑枝乙醇提取物对高尿酸血症小鼠的促尿酸排泄和肾脏保护作用。

Uricosuric and nephroprotective properties of Ramulus Mori ethanol extract in hyperuricemic mice.

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China.

出版信息

J Ethnopharmacol. 2012 Oct 11;143(3):896-904. doi: 10.1016/j.jep.2012.08.023. Epub 2012 Aug 29.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Ramulus Mori, the branch of Morus alba, is widely used in traditional Chinese medicine prescriptions to treat gout and hyperuricemia.

AIM OF THIS STUDY

To evaluate the uricosuric and nephroprotective effects of ethanol extract of Ramulus Mori (ERM) and explore its possible mechanisms in hyperuricemic mice.

MATERIALS AND METHODS

HPLC analysis was employed to determine the main constituents. Hyperuricemia was induced by potassium oxonate (250 mg/kg) in male mice. ERM (10, 20 and 40 mg/kg) was orally administered to hyperuricemic and normal mice for 7 days. Serum and urine levels of uric acid, creatinine and blood urea nitrogen (BUN) were measured. Simultaneously, renal mRNA and protein levels of mouse urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1) and organic cation/carnitine transporters (mOCT1/2, mOCTN1/2) were analyzed by RT-PCR and Western blotting methods.

RESULTS

ERM mainly contained mulberroside A, oxyresveratrol, 4-hydroxycinnamic acid, resveratrol, 7-hydroxycumarin and morin. ERM significantly reduced serum urate levels and increased 24h-urine urate excretion and fractional excretion of uric acid in hyperuricemic mice. It effectively restored oxonate-induced expression alteration of renal mURAT1, mGLUT9 and mOAT1, resulting in urate excretion enhancement. Moreover, ERM decreased serum creatinine and BUN levels and increased creatinine clearance, and up-regulated expression of mOCT1/2 and mOCTN1/2, contributing to kidney function improvement in this model.

CONCLUSION

These results suggest that ERM exerts the uricosuric and nephroprotective actions by the regulation of these renal organic ion transporters in hyperuricemic mice, and provide scientific support for the empirical use of Ramulus Mori.

摘要

民族药理学相关性

桑枝,即桑树的嫩枝,广泛用于传统中药方剂中,用于治疗痛风和高尿酸血症。

目的

评估桑枝乙醇提取物(ERM)的促尿酸排泄和肾脏保护作用,并探讨其在高尿酸血症小鼠中的可能机制。

材料和方法

采用高效液相色谱法分析确定主要成分。雄性小鼠用氧嗪酸钾(250mg/kg)诱导高尿酸血症。ERM(10、20 和 40mg/kg)连续 7 天灌胃给予高尿酸血症和正常小鼠。测定血清和尿液中尿酸、肌酐和血尿素氮(BUN)水平。同时,采用 RT-PCR 和 Western blot 方法分析小鼠尿酸转运体 1(mURAT1)、葡萄糖转运体 9(mGLUT9)、有机阴离子转运体 1(mOAT1)和有机阳离子/肉碱转运体(mOCT1/2、mOCTN1/2)的肾脏 mRNA 和蛋白水平。

结果

ERM 主要含有桑皮苷 A、氧化白藜芦醇、4-羟基肉桂酸、白藜芦醇、7-羟基香豆素和桑色素。ERM 可显著降低高尿酸血症小鼠的血清尿酸水平,增加 24 小时尿尿酸排泄量和尿酸排泄分数。它还能有效恢复氧嗪酸钾诱导的肾脏 mURAT1、mGLUT9 和 mOAT1 的表达改变,从而促进尿酸排泄。此外,ERM 降低了血清肌酐和 BUN 水平,增加了肌酐清除率,并上调了 mOCT1/2 和 mOCTN1/2 的表达,改善了该模型的肾功能。

结论

这些结果表明,ERM 通过调节高尿酸血症小鼠肾脏中的这些有机离子转运体发挥促尿酸排泄和肾脏保护作用,为桑枝的经验应用提供了科学依据。

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