Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion)

Med Sci Monit. 2017 Mar 4;23:1129-1140. doi: 10.12659/msm.903217.

Abstract

BACKGROUND The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. MATERIAL AND METHODS Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. RESULTS Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. CONCLUSIONS GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.

MeSH terms

  • Animals
  • Cholesterol / administration & dosage
  • Cholesterol / metabolism
  • Diet, High-Fat
  • Gynostemma
  • Hypercholesterolemia / metabolism
  • Hyperuricemia / blood
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / enzymology
  • Hyperuricemia / urine
  • Kidney / drug effects
  • Lipid Metabolism / drug effects
  • Male
  • Plant Extracts / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Uric Acid / metabolism
  • Xanthine Dehydrogenase / antagonists & inhibitors*
  • Xanthine Dehydrogenase / metabolism

Substances

  • Plant Extracts
  • gypenoside
  • Uric Acid
  • Cholesterol
  • Xanthine Dehydrogenase