Nasunin inhibits the lipopolysaccharide-induced pro-inflammatory mediator production in RAW264 mouse macrophages by suppressing ROS-mediated activation of PI3 K/Akt/NF-κB and p38 signaling pathways

Biosci Biotechnol Biochem. 2017 Oct;81(10):1956-1966. doi: 10.1080/09168451.2017.1362973. Epub 2017 Aug 16.

Abstract

Nasunin is a major anthocyanin in eggplant peel. The purpose of this study was to examine the anti-inflammatory effects of nasunin in lipopolysaccharide (LPS)-stimulated RAW264 macrophages and to identify the molecular mechanisms underlying these effects. We found that nasunin reduced the LPS-induced secretion of tumor necrosis factor-α, interleukin-6 and nitric oxide, and expression of inducible nitric oxide synthase in a dose-dependent manner. Nasunin diminished LPS-induced nuclear factor-κB (NF-κB) activation by suppressing the degradation of inhibitor of κB-α and nuclear translocation of p65 subunit of NF-κB. Nasunin also attenuated the phosphorylation of Akt and p38, signaling molecules involved in pro-inflammatory mediator production. Moreover, nasunin inhibited the intracellular accumulation of ROS, leading to the suppression of NF-κB activation, Akt and p38 phosphorylation, and subsequent pro-inflammatory mediator production. These findings suggest that nasunin exerts an anti-inflammatory effect and this effect is mediated, at least in part, by its antioxidant activity.

Keywords: Nasunin; anti-inflammation; antioxidant activity; macrophage.

MeSH terms

  • Animals
  • Anthocyanins / pharmacology*
  • Enzyme Activation / drug effects
  • Gene Expression Regulation, Enzymologic / drug effects
  • Inflammation Mediators / metabolism*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology*
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anthocyanins
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Reactive Oxygen Species
  • nasunin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases