Anti-inflammatory effect of prunetin via the suppression of NF-κB pathway

Prunetin is an O-methylated isoflavone, which is found in Prunus yedoensis. To date no report has been published on anti-inflammatory activities of prunetin. In the present study, the anti-inflammatory effect of prunetin on LPS-stimulated RAW 264.7 macrophage and LPS-induced septic shock model were investigated. Inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta) expressions were determined by western blot and or real-time-PCR (RT-PCR). To elucidate its underlying mechanism, nuclear factor-kappa B (NF-kappa b) activation and its downstream pathways were investigated by NF-kappa B transcription factor assay, reporter gene expression, and western blot. In vivo anti-inflammatory effects of prunetin were evaluated in LPS-induced endotoxemia. Promoter assay revealed that prunetin inhibits LPS-induced nitric oxide and prostaglandin E-2 production through the suppression of iNOS and COX-2 at the transcriptional level. In addition, prunetin inhibits NF-kappa B-dependent inflammatory responses by modulating I kappa B kinase (IIK)-inhibitor kappa B alpha (I kappa B alpha)-NF-kappa B signaling. Consistent with these results, prunetin significantly reduced serum levels of inflammatory cytokines and mortality in mice challenged with lipopolysaccharide. These findings offer a potential mechanism for the anti-inflammatory activity of prunetin. (C) 2013 Elsevier Ltd. All rights reserved.