Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipbpolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators; such as iNOS, TNF-alpha, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-kappa B signaling pathway, which inhibited NF-kappa B-dependent transcriptional activity, I kappa B alpha phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.