Anti-Hyperuricemic Effect of 2-Hydroxy-4-methoxy-benzophenone-5-sulfonic Acid in Hyperuricemic Mice through XOD

Molecules. 2018 Oct 17;23(10):2671. doi: 10.3390/molecules23102671.

Abstract

Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9).

Keywords: 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid; hyperuricemia; organic anion transporter 1; toxicity; xanthine oxidase.

MeSH terms

  • Animals
  • Benzophenones / administration & dosage*
  • Benzophenones / chemistry
  • Body Weight / drug effects
  • Gene Expression Regulation / drug effects
  • Glucose Transport Proteins, Facilitative / genetics*
  • Humans
  • Hyperuricemia / drug therapy*
  • Hyperuricemia / pathology
  • Hypoxanthine / administration & dosage
  • Kidney / drug effects
  • Mice
  • Molecular Docking Simulation
  • Organic Anion Transport Protein 1 / genetics*
  • Oxonic Acid / administration & dosage
  • Spleen / drug effects
  • Thymus Gland / drug effects
  • Xanthine Oxidase / antagonists & inhibitors
  • Xanthine Oxidase / genetics*

Substances

  • Benzophenones
  • Glucose Transport Proteins, Facilitative
  • Organic Anion Transport Protein 1
  • Slc22a6 protein, mouse
  • Slc2a9 protein, mouse
  • sulisobenzone
  • Hypoxanthine
  • potassium oxonate
  • Oxonic Acid
  • Xanthine Oxidase