Malibatol A regulates microglia M1/M2 polarization in experimental stroke in a PPARγ-dependent manner

J Neuroinflammation. 2015 Mar 14:12:51. doi: 10.1186/s12974-015-0270-3.

Abstract

Background: Activation of microglia plays a crucial role in immune and inflammatory processes after ischemic stroke. Microglia is reported with two opposing activated phenotypes, namely, classic phenotype (M1) and the alternative phenotype (M2). Inhibiting M1 while stimulating M2 has been suggested as a potential therapeutic approach in the treatment of stroke.

Findings: In this study, we indicated that a novel natural anti-oxidant extracted from the Chinese plant Hopea hainanensis, malibatol A (MA), decreased the infarct size and alleviated the brain injury after mice middle cerebral artery occlusion (MCAO). MA inhibited expression inflammatory cytokines in not only MCAO mice but also lipopolysaccharide (LPS)-stimulated microglia. Moreover, treatment of MA decreased M1 markers (CD16, CD32, and CD86) and increased M2 markers (CD206, YM-1) while promoting the activation of nuclear receptor PPARγ.

Conclusions: MA has anti-inflammatory effects in MCAO mice in a PPARγ-dependent manner, making it a potential candidate for stroke treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzamides / pharmacology
  • Benzamides / therapeutic use
  • Brain Infarction / etiology
  • Brain Infarction / prevention & control
  • Calcium-Binding Proteins / metabolism
  • Cell Polarity / drug effects*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / pathology*
  • Lipopolysaccharides / pharmacology
  • Mice
  • Microfilament Proteins / metabolism
  • Microglia / drug effects*
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Nitric Oxide Synthase Type II / metabolism
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / metabolism*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use*
  • Time Factors

Substances

  • Aif1 protein, mouse
  • Benzamides
  • Calcium-Binding Proteins
  • Cytokines
  • Lipopolysaccharides
  • Microfilament Proteins
  • Neuroprotective Agents
  • PPAR gamma
  • Pyridines
  • Stilbenes
  • T 0070907
  • malibatol A
  • Nitric Oxide Synthase Type II