Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages.
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.
Murakami
Yukio
Y
Department of Oral Diagnosis, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado City, Saitama 350-0283, Japan.
Shoji
Masao
M
Hirata
Atsushi
A
Tanaka
Shoji
S
Yokoe
Ichiro
I
Fujisawa
Seiichiro
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D051546:Cyclooxygenase 2; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008956:Models, Chemical; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009693:Nucleic Acid Hybridization; D010957:Plasmids / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D018076:DNA, Complementary; D008070:Lipopolysaccharides; D016328:NF-kappa B; C496603:dehydrodiisoeugenol; D005054:Eugenol; C036643:isoeugenol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases