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

Abstract

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.

• Authors: Yukio Murakami, Masao Shoji, Atsushi Hirata, Shoji Tanaka, Ichiro Yokoe, Seiichiro Fujisawa
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 434 Issue 2 Pg. 326-32 (Feb 15 2005) ISSN: 0003-9861 [Print] United States
• PMID: 15639233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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