Isoeugenol suppression of inducible nitric oxide synthase expression is mediated by down-regulation of NF-κB, ERK1/2, and p38 kinase

Chun Yeon Choi, Kyung Ran Park, Jung Hee Lee, Young Jin Jeon, Kwang Hyeon Liu, Sangtaek Oh, Dong Eun Kim, Sung Su Yea

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57 Scopus citations

Abstract

Isoeugenol, which is a naturally occurring o-methoxyphenol in a variety of foods and essential oils, is known to have anti-inflammatory effects, although the mechanism is not clear. In the present study, we investigated the effect of isoeugenol on NF-κB signaling leading to inducible nitric oxide synthase (iNOS) expression in RAW 264.7 murine macrophages stimulated with lipopolysaccharide (LPS). Isoeugenol markedly inhibited nitric oxide (NO) production in dose- and time-dependent manners. The decrease in NO production was found to correlate with a decrease in iNOS expression, as determined by Western blot analysis and real-time RT-PCR. To characterize further the inhibitory mechanisms of isoeugenol at the transcriptional level, we examined the DNA-binding and transcriptional activities of NF-κB. Isoeugenol inhibited NF-κB-dependent transcriptional activity and DNA-binding activity by decreasing the nuclear translocation of p65, which is a component of NF-κB. In addition, isoeugenol blocked signaling upstream of NF-κB activation, such as degradation of I-κBα and the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK), in LPS-stimulated RAW 264.7 cells. The isoeugenol analogues eugenol and allylbenzene also inhibited LPS-induced NF-κB signaling and iNOS expression, albeit with less potency than isoeugenol. These results suggest that isoeugenol and its analogues inhibit NO production and iNOS expression in LPS-stimulated RAW 264.7 cells, and that these effects are mediated, at least in part, by blocking the phosphorylation of ERK1/2 and p38 kinase, degradation of I-κBα, and activation of NF-κB.

Original languageEnglish (US)
Pages (from-to)151-159
Number of pages9
JournalEuropean Journal of Pharmacology
Volume576
Issue number1-3
DOIs
StatePublished - Dec 8 2007

Bibliographical note

Funding Information:
This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (No. R01-2007-000-20669-0).

Keywords

  • Eugenol
  • Extracellular signal-regulated kinase 1/2
  • Inducible nitric oxide synthase
  • Inhibitory κBα
  • Isoeugenol
  • Nuclear factor-κB
  • p38 kinase

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