title: Src/NF-κB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract.
abstract: BACKGROUND
  Archidendron clypearia Jack. (Fabaceae) has been traditionally used to treat various inflammatory diseases such as pain in the eyes. However, the antiinflammatory mechanism of A. clypearia has not been fully elucidated. This study examined the anti-inflammatory mechanism of a 95% methanol extract (Ac-ME) of A. clypearia in vitro and in vivo.
  
  
  METHODS
  The effect of Ac-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages and on symptoms of colitis in mouse induced by dextran sodium sulphate (DSS) was investigated. Molecular mechanisms underlying the inhibitory effects were elucidated by analyzing the activation of transcription factors and their upstream signaling as well as by evaluating the kinase activity of target enzymes in vitro and in vivo.
  
  
  RESULTS
  Ac-ME dose-dependently suppressed the secretion of nitric oxide (NO) and prostaglandin (PG)E₂ from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ac-ME clearly reduced mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α by the blockade of nuclear factor (NF)-κB activation and its upstream signaling events containing protein tyrosine kinase such as Syk and Src. In agreement with this, Ac-ME directly reduced the kinase activities of Src and Syk as well as the formation of molecular signaling complex including p85. DSS-induced colitis was also remarkably inhibited by this extract through the suppression of Src and IκBα phosphorylation.
  
  
  CONCLUSIONS
  Ac-ME displays strong anti-inflammatory activity in vivo by suppressing Src/Syk-mediated NF-κB activation which is linked to its ethno-pharmacological uses as an anti-gastritis remedy. Through preclinical studies, the potential therapeutic application will be tested further.
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Woo
authors.initials: W
authors.lastname: Seok Yang
authors.forename: Jaehwi
authors.initials: J
authors.lastname: Lee
authors.forename: Tae
authors.initials: T
authors.lastname: Woong Kim
authors.forename: Ji
authors.initials: J
authors.lastname: Hye Kim
authors.forename: Sukchan
authors.initials: S
authors.lastname: Lee
authors.forename: Man
authors.initials: M
authors.lastname: Hee Rhee
authors.forename: Sungyoul
authors.initials: S
authors.lastname: Hong
authors.forename: Jae
authors.initials: J
authors.lastname: Youl Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000378:metabolism; D007887:Fabaceae; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D008297:Male; D000432:Methanol / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000072377:Syk Kinase; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D016264:Dextran Sulfate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D019061:src-Family Kinases; D015232:Dinoprostone; D000432:Methanol