Anti-Inflammatory Effects of Grasshopper Ketone from Sargassum fulvellum Ethanol Extract on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells

J Microbiol Biotechnol. 2019 May 28;29(5):820-826. doi: 10.4014/jmb.1901.01027.

Abstract

This study evaluated the anti-inflammatory potential of a grasshopper ketone (GK) isolated from the brown alga Sargassum fulvellum on lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophage cell line. GK was isolated and purified from the n-hexane fraction and its structure was verified on the basis of NMR spectroscopic data. GK up to 100 μg/ml is not cytotoxic to RAW 264.7, and is an effective inhibitor of LPS-induced NO production in RAW 264.7 cells. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α was found significantly reduced in 0.1-100 μg/ml dose ranges of GK treatment (p < 0.05). We confirmed the dose-dependent and significant inhibition of iNOS and COX-2 proteins expression. In addition, it has been shown that GK induces anti-inflammatory effects by inhibiting MAPKs (ERK, JNK, and p38) and NF-κB p65 phosphorylation. Our results show that the anti-inflammatory properties of GK may be due to the inhibition of the NF-κB and MAPKs pathways, which are associated with the attenuation of cytokine secretion.

Keywords: Grasshopper ketone; anti-inflammation; mitogen-activated protein kinases; nuclear transcription factor kappa-B; sargassum fulvellum.

MeSH terms

  • Alkadienes / chemistry
  • Alkadienes / isolation & purification*
  • Alkadienes / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cyclohexanols / chemistry
  • Cyclohexanols / isolation & purification*
  • Cyclohexanols / pharmacology*
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Ethanol
  • Inflammation / drug therapy
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / adverse effects*
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Phosphorylation
  • RAW 264.7 Cells / drug effects*
  • Sargassum / chemistry*
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Alkadienes
  • Anti-Inflammatory Agents
  • Cyclohexanols
  • Cytokines
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • grasshopper ketone
  • Nitric Oxide
  • Ethanol
  • Cyclooxygenase 2
  • Mitogen-Activated Protein Kinases