Two enone fatty acids isolated from Gracilaria verrucosa suppress the production of inflammatory mediators by down-regulating NF-kappaB and STAT1 activity in lipopolysaccharide-stimulated RAW 264.7 cells

Arch Pharm Res. 2009 Mar;32(3):453-62. doi: 10.1007/s12272-009-1320-0. Epub 2009 Apr 23.

Abstract

Gracilaria verrucosa is a common marine red alga that has anti-oxidant and anti-cancer properties. Recently, we reported that anti-inflammatory constituents of G. verrucosa operate through an unknown mechanism. For this reason, we isolated two enone fatty acids from G. verrucosa and investigated their molecular mechanism in LPS-stimulated RAW264.7 cells. We found that the two compounds inhibited the production of inflammatory markers (nitric oxide, TNF-alpha, and IL-6) in a dose-dependent manner. We next studied the effects of G. verrucosa compounds on LPS-induced signaling pathways. The two compounds suppressed NF-kappaB reporter activity by interfering with nuclear translocation of NF-kappaB and suppressed JAK/STAT (p-STAT1) signaling. These results suggest that G. verrucosa inhibits the production of inflammatory mediators (NO, TNF-alpha, and IL-6) by suppressing the activation of NF-kappaB and the phosphorylation of STAT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Fatty Acids / isolation & purification
  • Fatty Acids / pharmacology*
  • Gracilaria* / chemistry
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / metabolism
  • Janus Kinases / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation
  • Promoter Regions, Genetic / drug effects
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Fatty Acids
  • Inflammation Mediators
  • Interleukin-6
  • Lipopolysaccharides
  • Rela protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • lipopolysaccharide, Escherichia coli O111 B4
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Janus Kinases