Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages

Arch Biochem Biophys. 2005 Feb 15;434(2):326-32. doi: 10.1016/


o-Methoxyphenols such as eugenol and isoeugenol exhibit anti-oxidant and anti-inflammatory activities, but at higher concentrations act as oxidants and potent allergens. We recently demonstrated the eugenol dimer bis-eugenol to be an efficient inhibitor of lipopolysaccharide (LPS)-induced inflammatory cytokine expression in macrophages without cytotoxicity. This result suggested that dimer compound of o-methoxyphenols may possess anti-inflammatory activity. Thus, we further synthesized dehydrodiisoeugenol and alpha-diisoeugenol from isoeugenols, and investigated whether these dimers could inhibit LPS-stimulated nuclear factor kappa B (NF-kappaB) activation and cyclooxygenase (COX)-2 gene expression, both of which are closely involved in inflammation and mutagenesis. The expression of the COX-2 gene was strongly inhibited by dehydrodiisoeugenol in RAW264.7 murine macrophages stimulated with LPS. In contrast, isoeugenol and alpha-diisoeugenol did not inhibit it. Dehydrodiisoeugenol also significantly inhibited LPS-stimulated phosphorylation-dependent proteolysis of inhibitor kappaB-alpha and transcriptional activity of NF-kappaB in the cells. These findings suggest that dehydrodiisoeugenol acts as a potent anti-inflammatory agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Blotting, Northern
  • Blotting, Western
  • Cell Line
  • Cyclooxygenase 2
  • DNA, Complementary / metabolism
  • Dimerization
  • Dose-Response Relationship, Drug
  • Eugenol / analogs & derivatives*
  • Eugenol / chemistry*
  • Eugenol / pharmacology*
  • Lipopolysaccharides / metabolism*
  • Macrophages / enzymology*
  • Mice
  • Models, Chemical
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Nucleic Acid Hybridization
  • Plasmids / metabolism
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Time Factors


  • Anti-Inflammatory Agents
  • DNA, Complementary
  • Lipopolysaccharides
  • NF-kappa B
  • dehydrodiisoeugenol
  • Eugenol
  • isoeugenol
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases