Icariin inhibits hydrogen peroxide-mediated cytotoxicity by up-regulating sirtuin type 1-dependent catalase and peroxiredoxin

Basic Clin Pharmacol Toxicol. 2010 Nov;107(5):899-905. doi: 10.1111/j.1742-7843.2010.00595.x.

Abstract

Previous studies suggest that flavonol icariin protects against neuron injury after oxygen and glucose deprivation by increasing SIRT1. This study demonstrates that icariin can inhibit H(2) O(2) -induced neurotoxicity. The neuroprotection of icariin enhances the antioxidant capacity through both a direct scavenging effect on over-produced free radicals and an indirect stimulating effect on the expression and activity of cellular antioxidant enzymes including catalase (CAT) and peroxiredoxin 1 (Prx1). The mechanism may be partially involved in the up-regulation of SIRT1. The SIRT1 antagonist can partly block this neuroprotection and the enhancement of CAT/Prx1 by icariin. These results indicate that the effect of icariin on H(2) O(2) -induced neurotoxicity is dependent on increasing SIRT1 and provides a potentially novel pharmacological strategy for stroke prevention and/or treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Catalase / biosynthesis*
  • Catalase / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • Hydrogen Peroxide / pharmacology*
  • Mice
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / enzymology
  • Neuroprotective Agents / pharmacology*
  • Oxidative Stress / drug effects
  • Peroxiredoxins / biosynthesis*
  • Peroxiredoxins / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sirtuin 1 / metabolism*
  • Spectrophotometry
  • Up-Regulation

Substances

  • Flavonoids
  • Neuroprotective Agents
  • Hydrogen Peroxide
  • Peroxiredoxins
  • Prdx1 protein, mouse
  • Catalase
  • Sirt1 protein, mouse
  • Sirtuin 1
  • icariin