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

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.