Sargaquinoic acid attenuates inflammatory responses by regulating NF-κB and Nrf2 pathways in lipopolysaccharide-stimulated RAW 264.7 cells

Int Immunopharmacol. 2015 Dec;29(2):693-700. doi: 10.1016/j.intimp.2015.09.007. Epub 2015 Oct 9.

Abstract

Myagropsis myagroides, a brown alga, showed strong anti-inflammatory activities in the previous studies. In this study, we isolated a strong anti-inflammatory compound, sargaquinoic acid (SQA), from M. myagroides and investigated the anti-inflammatory action using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. SQA suppressed the production of inducible nitric oxide synthase and cyclooxygenase-2 in LPS-stimulated cells as well as that of reactive oxygen species. As a result, SQA inhibited the production of NO, prostaglandin E2, and pro-inflammatory cytokines. LPS-induced transcriptional activation of nuclear factor-κB (NF-κB) was remarkably inhibited by SQA treatment through the prevention of inhibitor κB-α degradation. The regulation of NF-κB activation was also mediated by the phosphorylation of ERK and Akt in LPS-stimulated RAW 264.7 cells. Moreover, SQA induced the production of heme oxygenase 1 via activation of transcription factor Nrf2. These results indicate that SQA inhibits the LPS-induced expression of inflammatory mediators via suppression of ERK and Akt-mediated NF-κB pathway as well as up-regulation of Nrf2/HO-1 pathway, indicating that SQA has a potential therapeutic and preventive application in various inflammatory diseases.

Keywords: Anti-inflammation; Antioxidant; Myagropsis myagroides; NF-κB; Nrf2; Sargaquinoic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry
  • Alkenes / pharmacology*
  • Animals
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Gene Expression Regulation / drug effects*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Inflammation / drug therapy*
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Phaeophyceae

Substances

  • Alkenes
  • Benzoquinones
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • sargaquinoic acid
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Cyclooxygenase 2