Polyozellin inhibits nitric oxide production by down-regulating LPS-induced activity of NF-kappaB and SAPK/JNK in RAW 264.7 cells

Polyozellin, isolated from Polyozellus multiplex (Thelephoraceae), was investigated for its anti-inflammatory activity in the murine macrophage cell line RAW 264.7. Polyozellin inhibited both lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression in a dose-dependent manner. The effects of polyozellin on the activation of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases in these cells were studied in order to elucidate the underlying mechanism. Polyozellin suppressed the activation of both LPS-induced NF-kappaB and the stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), but had no effect on the extracellular signal-regulated kinase (ERK) or p38. These data suggest that polyozellin suppresses iNOS expression by inhibiting the activation of NF-kappaB and SAPK/JNK, leading to the inhibition of NO production.