RRC ID 42292
Author Murakami Y, Shoji M, Hirata A, Tanaka S, Yokoe I, Fujisawa S.
Title Dehydrodiisoeugenol, an isoeugenol dimer, inhibits lipopolysaccharide-stimulated nuclear factor kappa B activation and cyclooxygenase-2 expression in macrophages.
Journal Arch Biochem Biophys
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.
Volume 434(2)
Pages 326-32
Published 2005-2-15
DOI 10.1016/j.abb.2004.11.013
PII S0003-9861(04)00661-7
PMID 15639233
MeSH 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
IF 3.391
Times Cited 54
Human and Animal Cells RAW 264(RCB0535)