Resveratrol inhibits oligomeric Aβ-induced microglial activation via NADPH oxidase

Mol Med Rep. 2015 Oct;12(4):6133-9. doi: 10.3892/mmr.2015.4199. Epub 2015 Aug 7.

Abstract

Microglia‑mediated neuroinflammation is key in the pathogenesis of Alzheimer's disease (AD). Several studies have suggested that NADPH oxidase contributes to microglia‑mediated neuroinflammation. Resveratrol, which is a natural polyphenolic compound, exerts neuroprotective effects in AD due to its anti‑inflammatory properties. The present study aimed to investigate the effects of resveratrol on the activation of oligomeric amyloid β (oAβ)‑induced BV‑2 microglia, and to determine the role of NADPH oxidase in these effects. Microglial proliferation was measured by high‑content screening cell counting and using a bromodeoxyuridine incorporation assay. In addition, the levels of reactive oxygen species (ROS), nitric oxide (NO), tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were assessed. The results of the present study demonstrated that resveratrol inhibited the proliferation of oAβ‑induced microglia and the production of pro‑inflammatory factors, including ROS, NO, TNF‑α and IL‑1β. Subsequent mechanistic investigations demonstrated that resveratrol inhibited the oAβ‑induced mRNA and protein expression levels of p47phox and gp91phox. These results suggested that NADPH oxidase may be a potential target for AD treatment, and resveratrol may be a valuable natural product possessing therapeutic potential against AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Interleukin-1beta / metabolism
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microglia / cytology
  • Microglia / drug effects*
  • NADPH Oxidase 2
  • NADPH Oxidases / metabolism*
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Resveratrol
  • Stilbenes / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Amyloid beta-Peptides
  • Anti-Inflammatory Agents
  • IL1B protein, mouse
  • Interleukin-1beta
  • Membrane Glycoproteins
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Stilbenes
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Cybb protein, mouse
  • NADPH Oxidase 2
  • NADPH Oxidases
  • neutrophil cytosolic factor 1
  • Resveratrol