The inhibitory activity of atractylenolide Ш, a sesquiterpenoid, on IgE-mediated mast cell activation and passive cutaneous anaphylaxis (PCA)
2013
Zhang, Nan-nan | Park, Dong Ki | Park, Hye-Jin
ETHNOPHARMACOLOGICAL RELEVANCE: AT Ш, a sesquiterpenoid, is the major component of Atractylodes japonica Koidz that has been used as a traditional oriental medicine. AIM OF THE STUDY: We investigated the anti-allergic activity of AT Ш and its mechanism of action. MATERIALS AND 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 [Ca²⁺]i in mast cells. RESULTS: AT Ш significantly inhibited IgE/Ag-mediated degranulation with an IC₅₀ value (36±4μM) in RBL-2H3 cells without affecting cell viability. It also suppressed IgE/Ag-mediated passive cutaneous anaphylaxis (PCA) response with an ED₅₀ value (65±41mg/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 [Ca²⁺]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.
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