title: Anti-inflammatory effect of prunetin via the suppression of NF-κB pathway.
abstract: 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.
authors.affiliation: Department of Herbology, College of Oriental Medicine, Kyung-Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Gabsik
authors.initials: G
authors.lastname: Yang
authors.forename: Inhye
authors.initials: I
authors.lastname: Ham
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Choi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012772:Shock, Septic / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D007529:Isoflavones; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C083295:prunetin; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases
keywords: Isoflavone; NF-κb; Prunetin; Prunus yedoensis; RAW 264.7; Sepsis