title: Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.
abstract: OBJECTIVE
  Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS.
  
  
  METHODS
  The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-α, IL-6 and IL-1β were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-κB activation and its pathways were investigated by electrophoretic mobility shift assay, reporter gene and Western blot assays. In addition, the in vivo anti-inflammatory effects of arvelexin were evaluated in endotoxaemia induced with LPS.
  
  
  RESULTS
  Promoter assays for iNOS and COX-2 revealed that arvelexin inhibited LPS-induced NO and prostaglandin E(2) production through the suppression of iNOS and COX-2 at the level of gene transcription. In addition, arvelexin inhibited NF-κB-dependent inflammatory responses by modulating a series of intracellular events of IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signalling. Moreover, arvelexin inhibited IKKβ-elicited NF-κB activation as well as iNOS and COX-2 expression. Serum levels of NO and inflammatory cytokines and mortality in mice challenged injected with LPS were significantly reduced by arvelexin.
  
  
  CONCLUSIONS
  Arvelexin down-regulated inflammatory iNOS, COX-2, TNF-α, IL-6 and IL-1β gene expression in macrophages interfering with the activation of IKKβ and p38 mitogen-activated protein kinase, and thus, preventing NF-κB activation.
authors: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.
authors: Ji-Sun
authors: JS
authors: Shin
authors: Young-Su
authors: YS
authors: Noh
authors: Yong Sup
authors: YS
authors: Lee
authors: Young-Wuk
authors: YW
authors: Cho
authors: Nam-In
authors: NI
authors: Baek
authors: Myung-Sook
authors: MS
authors: Choi
authors: Tae-Sook
authors: TS
authors: Jeong
authors: Eunkyung
authors: E
authors: Kang
authors: Hae-Gon
authors: HG
authors: Chung
authors: Kyung-Tae
authors: KT
authors: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D029741:Brassica rapa / Q000737:chemistry; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D012772:Shock, Septic / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors; D000094162:Phytoalexins
chemical_list: D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D051550:I-kappa B Kinase; D007211:Indoles; D053583:Interleukin-1beta; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D009589:Nitrogen Oxides; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C500823:arvelexin; D000094162:Phytoalexins