title: Nitidine chloride inhibits LPS-induced inflammatory cytokines production via MAPK and NF-kappaB pathway in RAW 264.7 cells.
abstract: BACKGROUND
  Zanthoxylum nitidium (Roxb.) DC. has long been used as a traditional herbal medicine for inflammatory diseases such as rheumatic arthritis and peridentitis. However, the anti-inflammatory mechanism of Nitidine chloride has not been fully elucidated.
  
  
  OBJECTIVE
  To determine the anti-inflammatory effects and mechanism of Nitidine chloride (NTD), a pentacyclic alkaloid is isolated from the root of Z. nitidium, in murine macrophages.
  
  
  METHODS
  Anti-inflammatory properties of NTD were investigated using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro model. The pro-inflammatory cytokines were evaluated by real-time RT-PCR and ELISA. Furthermore, intracellular signaling pathways were analyzed by Western blot and Immunofluorescence staining using specific antibodies.
  
  
  RESULTS
  NTD significantly reduced the production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6 in both RNA and protein level. Moreover, transcriptional activity of NF-кB as well as the phosphorylation of mitogen-activated protein kinases (MAPKs) in LPS-treated RAW 264.7 was significantly inhibited by NTD in a dose dependent manner. These results suggested that NTD exerts an anti-inflammatory property by inhibiting TNF-α, IL-1β, and IL-6 production in association with reduced NF-κB and MAPK signaling pathways in RAW 264.7 cells.
  
  
  CONCLUSIONS
  These results suggested that NTD exerts an anti-inflammatory property by inhibiting TNF-α, IL-1β, and IL-6 production in association with reduced NF-κB and MAPK signaling pathways in RAW 264.7 cells. Nitidine chloride inhibits LPS-induced TNF alpha, IL-1beta and IL-6 production via the suppression of phosphorylation of MAPK and the translocation of p65. In addition, these results revealed a novel role of NTD in regulation of inflammatory diseases.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.forename: Bing
authors.initials: B
authors.lastname: Du
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D053119:Benzophenanthridines / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides; D008516:Medicine, Chinese Traditional; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology; D032106:Zanthoxylum
chemical_list: D000893:Anti-Inflammatory Agents; D053119:Benzophenanthridines; D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; C013615:nitidine; D020928:Mitogen-Activated Protein Kinases