Suppression of lipopolysaccharide-stimulated inducible nitric oxide synthase (iNOS) expression by a novel humulene derivative in macrophage cells.
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-kappaB, indicating that regulation of NF-kappaB activity might be involved in the inhibition of NO production by 5-hydroxyzerumbone. 5-Hydroxyzerumbone, however, did not affect the degradation of IkappaB-alpha 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-kappaB activation and HO-1 induction in macrophage cells.
Min
Hye-Young
HY
College of Pharmacy and Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.
Kim
Moon Sun
MS
Jang
Dae Sik
DS
Park
Eun-Jung
EJ
Seo
Eun-Kyoung
EK
Lee
Sang Kook
SK
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007165:Immunosuppression Therapy; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects; D030521:Zingiberaceae; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C505178:5-hydroxy-2E,6E,9E-humulatrien-8-one; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases