Pycnogenol Attenuates the Release of Proinflammatory Cytokines and Expression of Perilipin 2 in Lipopolysaccharide-Stimulated Microglia in Part via Inhibition of NF-κB and AP-1 Activation

PLoS One. 2015 Sep 14;10(9):e0137837. doi: 10.1371/journal.pone.0137837. eCollection 2015.

Abstract

Over activation of microglia results in the production of proinflammatory agents that have been implicated in various brain diseases. Pycnogenol is a patented extract from French maritime pine bark (Pinus pinaster Aiton) with strong antioxidant and anti-inflammatory potency. The present study investigated whether pycnogenol may be associated with the production of proinflammatory mediators in lipopolysaccharide-stimulated BV2 (mouse-derived) microglia. It was found that pycnogenol treatment was dose-dependently associated with significantly less release of nitricoxide (NO), TNF-α, IL-6 and IL-1β, and lower levels of intercellular adhesion molecule1 (ICAM-1) and perilipin 2 (PLIN2). Furthermore, this effect was replicated in primary brain microglia. Levels of inducible NO synthase mRNA and protein were attenuated, whereas there was no change in the production of the anti-inflammatory cytokine IL-10. Further evidence indicated that pycnogenol treatment led to the suppression of NF-κB activation through inhibition of p65 translocation into the nucleus and inhibited DNA binding of AP-1, suggesting that these proinflammatory factors are associated with NF-κB and AP-1. We conclude that pycnogenol exerts anti-inflammatory effects through inhibition of the NF-κB and AP-1pathway, and may be useful as a therapeutic agent in the prevention of diseases caused by over activation of microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Cytokines / metabolism*
  • Dose-Response Relationship, Drug
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Inflammation / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Perilipin-2
  • Plant Extracts
  • Transcription Factor AP-1 / metabolism*

Substances

  • Cytokines
  • Flavonoids
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Perilipin-2
  • Plant Extracts
  • Plin2 protein, mouse
  • Transcription Factor AP-1
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • pycnogenols
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse

Grant support

This work is supported by Grant 81100216 from the National Natural Science Foundation of China Youth Fund Project; Grant 2013693 from the Scientific Research Foundation for the Returned Scholars, State Education Ministry; Grand 20131148 from Research Fund for the Doctoral Program of Higher Education of Liaoning Province. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.