Suppression of lipopolysaccharide-stimulated inducible nitric oxide synthase (iNOS) expression by a novel humulene derivative in macrophage cells

Hye Young Min, Moon Sun Kim, Dae Sik Jang, Eun Jung Park, Eun Kyoung Seo, Sang Kook Lee

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30 Scopus citations

Abstract

In our previous study, we reported the isolation of a novel humulene derivative, 5-hydroxyzerumbone, from Zingiber zerumbet and its inhibitory activity on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 mouse macrophage cells. This study was performed to examine its mechanism of action on the regulation of NO production. 5-Hydroxyzerumbone inhibited the expressions of iNOS mRNA and protein in a concentration-dependent manner. Treatment with 5-hydroxyzerumbone also induced the expression of heme oxygenase-1 (HO-1) in macrophage cells. In addition, 5-hydroxyzerumbone inhibited LPS-induced transcriptional activation of NF-κB, indicating that regulation of NF-κB activity might be involved in the inhibition of NO production by 5-hydroxyzerumbone. 5-Hydroxyzerumbone, however, did not affect the degradation of IκB-α and the activation of p38 and ERK in LPS-treated cells. Taken together, these results suggest that down-regulation of LPS-induced NO production by 5-hydroxyzerumbone is mediated by the suppression of iNOS expression through the modulation of NF-κB activation and HO-1 induction in macrophage cells.

Original languageEnglish
Pages (from-to)844-849
Number of pages6
JournalInternational Immunopharmacology
Volume9
Issue number7-8
DOIs
StatePublished - Jul 2009

Bibliographical note

Funding Information:
This work was supported by a grant from KonKook University, Chungju funded by the Ministry of Science and Technology through the Bio-food and drug Research Center of Korea (R12-2003-003-01001-0) and a grant no. R15-2006-020 from the National Core Research Center (NCRC) program of the Ministry of Education, Science and Technology (MEST) and the Korea Science and Engineering Foundation (KOSEF) through the Center for Cell Signaling and Drug Discovery Research at Ewha Womans University.

Keywords

  • 5-hydroxyzerumbone
  • Heme oxygenase-1 (HO-1)
  • Inducible nitric oxide synthase (iNOS)
  • NF-κB
  • Nitric oxide (NO)

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