Malibatol A protects against brain injury through reversing mitochondrial dysfunction in experimental stroke

Neurochem Int. 2015 Jan:80:33-40. doi: 10.1016/j.neuint.2014.11.003. Epub 2014 Nov 20.

Abstract

Ischemic stroke is particularly susceptible to free radicals mediated secondary neuronal damage, especially mitochondrial dysfunction. Malibatol A (MA), a novel resveratrol oligomer, has shown potential antioxidant property in vitro. But little is known about its effect on central nervous system (CNS) in vivo. In the present study, the effect of MA was evaluated in focal cerebral ischemia induced by right middle cerebral artery occlusion (MCAO) in mice. MA at the dose of 20 mg/kg was administered by caudal-vein injection within 15 min after reperfusion. At 24 h after cerebral ischemia/reperfusion (I/R) injury, ameliorated neurological scores and reduced infarct volume was observed in MA treated group. Also, MA treatment restored the increased levels of reactive oxygen species (ROS), 3-Nitrotyrosine (3-NT), and 4-Hydroxynonenal (4-HNE) induced by MCAO. The activities of respiratory enzyme complex I, III and mitochondrial transmembrane potential (Δ<PSI>m) were effectively preserved compared with MCAO group through MA treatment. Western blot analysis showed a marked increase in Bcl-2 and decrease in Bax expression after MA treatment as compared with MCAO group. Moreover, MA treatment prevented release of cytochrome c from mitochondria into cytoplasm and blunted activities of caspase-9 and caspase-3. Collectively, the present study indicates that MA can ameliorate MCAO-induced mitochondrial dysfunction, and this might partially contribute to its protective effect on brain damage after 24 h of I/R injury.

Keywords: Ischemic stroke; Malibatol A; Mitochondria; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Brain Injuries / prevention & control*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • Stroke / drug therapy*
  • Stroke / metabolism
  • Stroke / pathology

Substances

  • Neuroprotective Agents
  • Stilbenes
  • malibatol A