4-Hydroxy-2,3-Dimethyl-2-Nonen-4-Olide Has an Inhibitory Effect on Pro-Inflammatory Cytokine Production in CpG-Stimulated Bone Marrow-Derived Dendritic Cells

Mar Drugs. 2016 May 4;14(5):88. doi: 10.3390/md14050088.

Abstract

This study was intended to assess the anti-inflammatory properties of 4-hydroxy-2,3-dimethyl-2-nonen-4-olide (Comp) isolated from Ulva pertusa Kjellman on production of pro-inflammatory cytokines. Comp revealed remarkable inhibitory effects on production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Comp pre-treatment in the CpG DNA-stimulated BMDCs exhibited strong inhibition of interleukin (IL)-12 p40 and IL-6 production with IC50 values ranging from 7.57 ± 0.2 to 10.83 ± 0.3, respectively. It revealed an inhibitory effect on the phosphorylation of ERK1/2, JNK1/2, and p38, and on activator protein (AP)-1 reporter activity. Comp displayed noteworthy inhibitory effects on phosphorylation and degradation of IκBα, and on NF-κB reporter activity. In summary, these data propose that Comp has substantial anti-inflammatory properties and warrants further study concerning its potential use as a therapeutic agent for inflammation-associated maladies.

Keywords: 4-hydroxy-2,3-dimethyl-2-nonen-4-olide; activator protein-1; inflammation; pro-inflammatory cytokine.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Bone Marrow / drug effects*
  • CpG Islands / drug effects*
  • Cytokines / metabolism*
  • Dendritic Cells / drug effects*
  • Female
  • Inflammation / drug therapy*
  • Interleukin-12 / metabolism
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism
  • Ulva / chemistry*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Interleukin-6
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • NF-KappaB Inhibitor alpha
  • Interleukin-12