Icariin protects against brain injury by enhancing SIRT1-dependent PGC-1alpha expression in experimental stroke

Neuropharmacology. Jul-Aug 2010;59(1-2):70-6. doi: 10.1016/j.neuropharm.2010.03.017. Epub 2010 Apr 8.

Abstract

Icariin (ICA) has neuroprotection in oxygen-glucose deprivation (OGD) neurons by increasing Sirtuin1 (SIRT1). However, little is known about the role of ICA on stroke. SIRT1 is a class III histone deacetylase and activates peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) which stimulates mitochondrial activity. This study aims to investigate the expression of SIRT1 and PGC-1alpha during ICA's neuroprotection against ischemia. In vivo, behavioral test, infarct size and brain water content were evaluated on middle cerebral artery occlusion (MCAO) mouse models treated by ICA/saline. In vitro, primary cortical neurons were tortured by OGD in the presence of ICA or SIRT1 inhibitor III or PGC-1alpha siRNA. Cell viability and mortality were measured by MTT and flow cytometer assay. Knockdown efficiency of PGC-1alpha siRNA was measured by real time PCR. Expressions of SIRT1 and PGC-1alpha were also investigated. In result, neurological scores, infarct size and brain edema were all significantly improved, the cortical expressions of SIRT1 and PGC-1alpha were higher with ICA compared to the control (P < 0.05), and reversed by SIRT1 inhibitor III/PGC-1alpha siRNA. In conclusion, ICA protects against brain ischemic injury by increasing the SIRT1 and PGC-1alpha expression, potentially to be a neuroprotectant for ischemic brain injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Edema / drug therapy
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Brain Injuries / drug therapy*
  • Brain Injuries / metabolism
  • Brain Injuries / prevention & control
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Male
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Random Allocation
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / metabolism*
  • Stroke / drug therapy
  • Stroke / metabolism
  • Stroke / pathology
  • Trans-Activators / metabolism*
  • Transcription Factors

Substances

  • Flavonoids
  • Neuroprotective Agents
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Trans-Activators
  • Transcription Factors
  • Sirt1 protein, mouse
  • Sirtuin 1
  • icariin