title: Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells.
abstract: BACKGROUND
  Activation of macrophage is involved in many inflammation diseases. Lipopolysaccharide (LPS) is a powerful inflammatory signal contributing to monocytes/macrophages activation associated with increased proinflammatory cytokines expressions. We recently identified that vaccarin was expected to protect endothelial cells from injury. Hypaphorine was abundantly found in vaccaria semen. However, the potential roles and underlying mechanisms of vaccaria hypaphorine on macrophage inflammation have been poorly defined.
  
  
  METHODS
  This study was designed to determine the effects of vaccaria hypaphorine on LPS-mediated inflammation in RAW 264.7 cells.
  
  
  RESULTS
  In this study, we demonstrated that vaccaria hypaphorine dramatically ameliorated LPS-induced nitric oxide (NO) release and productions of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, monocyte chemoattractant protein 1 (MCP-1) and prostaglandin E2 (PGE2) in RAW 264.7 cells. LPS-stimulated expressions of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were down-regulated by vaccaria hypaphorine. Furthermore, vaccaria hypaphorine retarded LPS-induced phosphorylation of ERK, nuclear factor kappa beta (NFκB), NFκB inhibitor IκBα, and IKKβ. Immunofluorescence staining revealed that vaccaria hypaphorine eliminated the nuclear translocation of NFκB in LPS-treated RAW 264.7 cells.
  
  
  CONCLUSIONS
  It was seen that vaccaria hypaphorine counteracted inflammation via inhibition of ERK or/and NFκB signaling pathways. Collectively, we concluded that vaccaria hypaphorine can be served as an anti-inflammatory candidate.
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Haijian
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory of Natural Medicine, School of Pharmaceutical Science, Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Bao
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
authors.forename: Xuexue
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Basic Medicine, Wuxi Medical School, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China. qiulydoc@sina.com.
authors.forename: Liying
authors.initials: L
authors.lastname: Qiu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D061986:MCF-7 Cells; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D000067996:RAW 264.7 Cells; D031245:Vaccaria / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007211:Indoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; C001529:lenticin
keywords: COX-2; ERK; Hypaphorine; Inflammation; NFκB; iNOS