prunetin and Shock--Septic

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-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) expressions were determined by western blot and or realtime-PCR (RT-PCR). To elucidate its underlying mechanism, nuclear factor-kappa B (NF-κb) activation and its downstream pathways were investigated by NF-κB 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 E2 production through the suppression of iNOS and COX-2 at the transcriptional level. In addition, prunetin inhibits NF-κB-dependent inflammatory responses by modulating IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB 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.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Interleukin-1beta; Interleukin-6; Isoflavones; Macrophages; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Prostaglandin-Endoperoxide Synthases; Real-Time Polymerase Chain Reaction; Shock, Septic; Tumor Necrosis Factor-alpha