title: The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA).
abstract: BACKGROUND
  AT Ш, a sesquiterpenoid, is the major component of Atractylodes japonica Koidz that has been used as a traditional oriental medicine.
  
  
  OBJECTIVE
  We investigated the anti-allergic activity of AT Ш and its mechanism of action.
  
  
  METHODS
  The released amount of β-hexosaminidase in mast cells, a key parameter of degranulation, was measured. Anti-allergic potential of AT Ш was evaluated using passive cutaneous anaphylaxis in vivo. The anti-allergic mechanism of AT Ш was investigated by immunoblotting analysis, RT-PCR and measurement of [Ca(2+)]i in mast cells.
  
  
  RESULTS
  AT Ш significantly inhibited IgE/Ag-mediated degranulation with an IC(50) value (36 ± 4 μM) in RBL-2H3 cells without affecting cell viability. It also suppressed IgE/Ag-mediated passive cutaneous anaphylaxis (PCA) response with an ED(50) value (65 ± 41 mg/kg) in vivo. AT Ш suppressed the production of interleukin (IL-4) and tumor necrosis factor (TNF)-alpha mRNAs more potent than the Src-family kinase inhibitor PP2 in RBL-2H3 cells at all concentrations. In order to elucidate the anti-allergic mechanisms of AT Ш in mast cells, we examined the activated levels of signaling molecules. AT Ш inhibited the phosphorylation of Lyn, Fyn, Syk, LAT, PLCγ, Gab2, Akt, p38, and JNK kinases expression. IgE/Ag-mediated [Ca(2+)]i elevation was significantly inhibited by AT Ш.
  
  
  CONCLUSIONS
  Our study suggests that AT Ш might be used as a therapeutic agent for allergic diseases.
authors.affiliation: Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
authors.forename: Nan-nan
authors.initials: NN
authors.lastname: Zhang
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Park
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007073:Immunoglobulin E / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007424:Intracellular Fluid / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; D016207:Cytokines; D007783:Lactones; D012717:Sesquiterpenes; C424802:atractylenolide III; D007073:Immunoglobulin E; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium