The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA).

AT Ш, a sesquiterpenoid, is the major component of Atractylodes japonica Koidz that has been used as a traditional oriental medicine. We investigated the anti-allergic activity of AT Ш and its mechanism of action. 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. 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. Our study suggests that AT Ш might be used as a therapeutic agent for allergic diseases. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Citation

Nan-nan Zhang, Dong Ki Park, Hye-Jin Park. The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA). Journal of ethnopharmacology. 2013 Jan 9;145(1):278-85

Mesh Tags

Substances

PMID: 23149288

search → result