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

• Published in: Archives of biochemistry and biophysics 2005-02, Vol.434 (2), p.326-332
• Main Authors: Murakami, Yukio, Shoji, Masao, Hirata, Atsushi, Tanaka, Shoji, Yokoe, Ichiro, Fujisawa, Seiichiro
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-oxidants; Blotting, Northern; Blotting, Western; Cell Line; COX-2; Cyclooxygenase 2; Dehydrodiisoeugenol; Dimerization; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Eugenol - analogs & derivatives; Eugenol - chemistry; Eugenol - pharmacology; Isoeugenol; Lipopolysaccharides - metabolism; LPS; Macrophage; Macrophages - enzymology; Mice; Models, Chemical; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; NF-κB; Nucleic Acid Hybridization; o-Methoxyphenol; Plasmids - metabolism; Prostaglandin-Endoperoxide Synthases - biosynthesis; Time Factors; α-Diisoeugenol
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2004.11.013

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 α-diisoeugenol from isoeugenols, and investigated whether these dimers could inhibit LPS-stimulated nuclear factor kappa B (NF-κB) 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 α-diisoeugenol did not inhibit it. Dehydrodiisoeugenol also significantly inhibited LPS-stimulated phosphorylation-dependent proteolysis of inhibitor κB-α and transcriptional activity of NF-κB in the cells. These findings suggest that dehydrodiisoeugenol acts as a potent anti-inflammatory agent.