| Polyozellin, isolated from Polyozellus multiplex, was investigated for its anti-inflammatory activity in the murine macrophage cell line RAW 264.7. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, polyozelllin inhibits nitric oxide (NO) production in a dose-dependent manner and abrogates inducible nitric oxide synthase (iNOS) gene expression. To investigate the mechanism by which polyozellin inhibits murine iNOS gene expression, we examined activation of mitogenactivated protein kinases (MAP kinases) and nuclear factor-KB (NF-κB) in these cells. Addition of polyozellin inhibited phosphorylation of c-Jun NH2-terminal kinase (JNK) but not that of extracellular signal-regulated kinase (ERK) or p38 mitogen-activated protein kinase. In addition, polyozellin significantly inhibited the DNA binding activity of NF-kB. These results suggest that polyozellin acts to inhibit inflammation through inhibition of NO production and iNOS expression through blockade of NF-κB and JNK activation. |