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Wednesday, 15 April 2015

Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia, a traditional Chinese herbal medicine

Volume 162, 13 March 2015, Pages 362–368
Research Paper

Anti-hyperuricemia effects of allopurinol are improved by Smilax riparia, a traditional Chinese herbal medicine

 

Abstract

Ethnopharmacological relevance

The roots and rhizomes of Smilax riparia are called “Niu-Wei-Cai” in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether Smilax riparia could enhance allopurinol׳s effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate.

Materials and methods

We examined the effects of allopurinol (5 mg/kg) administration alone or in combination with Smilax riparia saponins (SRS, 500 mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice.

Results

Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum and urine creatinine and BUN supported these observations. The attenuation of hyperuricemia-induced renal dysfunction was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1.

Conclusion

The anti-hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions.

Graphical abstract

Full-size image (17 K)

Abbreviations

  • BUN, blood urea nitrogen;
  • BuOH, n-butyl alcohol;
  • CMC-Na, carboxymethyl cellulose sodium;
  • Cr, creatinine;
  • EtOH, ethyl alcohol;
  • FEUA, fraction excretion of uric acid;
  • HPLC, high-performance liquid chromatography;
  • HPLC-ELSD, HPLC-evaporative light scattering detector;
  • HR-ESI-MS, high-resolution electrospray ionization mass spectrometry;
  • IR, infrared spectrophotometer;
  • mGAPDH, glyceraldehyde-3-phosphate dehydrogenase;
  • mGLUT9, mouse glucose transporter 9;
  • mOAT1, mouse organic anion transporter 1;
  • mURAT1, mouse urate transporter 1;
  • MS, mass spectrometer;
  • NMR, nuclear magnetic resonance;
  • RP, reversed phase;
  • SRS, Smilax riparia saponins;
  • TCM, traditional Chinese medicine;
  • UA, uric acid;
  • UV, ultraviolet spectrophotometer;
  • XOD, xanthine oxidase

Keywords

  • Smilax riparia;
  • Smilax riparia saponins;
  • SRS;
  • Allopurinol;
  • Hyperuricemia;
  • Gout

Correspondence to: Tang Center for Herbal Medicine Research, The Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC 4028, Chicago, IL 60637, USA. Tel.: +1 773 702 1916; fax: +1 773 834 0601.