Anti-inflammatory effect of alpha-linolenic acid and its mode of action through the inhibition of nitric oxide production and inducible nitric oxide synthase gene expression via NF-kappaB and mitogen-activated protein kinase pathways

J Agric Food Chem. 2007 Jun 27;55(13):5073-80. doi: 10.1021/jf0702693. Epub 2007 Jun 2.

Abstract

Alpha-linolenic acid (ALA) isolated from Actinidia polygama fruits exhibits potent anti-inflammatory activity with an unknown mechanism. To elucidate the molecular mechanisms of ALA on pharmacological and biochemical actions in inflammation, we examined the effect of ALA on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophages cell line, RAW 264.7. We found that ALA has a strong inhibitory effect on the production of NO. ALA also inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha) gene expressions induced by LPS. To explore the mechanisms associated with the inhibition of iNOS gene expression by ALA, we investigated its effect on LPS-induced nuclear factor-kappaB (NF-kappaB) activation. Treatment with ALA reduced a translocation of NF-kappaB subunit and NF-kappaB-dependent transcriptional activity. The activation of NF-kappaB was inhibited by prevention of the degradation of inhibitory factor-kappaBalpha. We also found that ALA inhibited LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs). In addition, the antinociceptive effect of ALA was also assessed by means of the acetic acid-induced abdominal constriction test and Randall-Selitto assay. ALA (5 and 10 mg/kg) showed the potent antinociceptive effects in these animal models. Taken together, these results suggest that ALA downregulates inflammatory iNOS, COX-2, and TNF-alpha gene expressions through the blocking of NF-kappaB and MAPKs activations in LPS-stimulated RAW 264.7 cells, which may be the mechanistic basis for the anti-inflammatory effect of ALA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Gene Expression / drug effects
  • Macrophages
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type II / genetics*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • alpha-Linolenic Acid / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • alpha-Linolenic Acid
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases
  • Mitogen-Activated Protein Kinases