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

摘要

Ethnopharmacological relevance: AT III, 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 III 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 III was evaluated using passive cutaneous anaphylaxis in vivo. The anti-allergic mechanism of AT III was investigated by immunoblotting analysis, RT-PCR and measurement of [Ca 2+]i in mast cells. Results: AT III significantly inhibited IgE/Ag-mediated degranulation with an IC50 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 III 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 III in mast cells, we examined the activated levels of signaling molecules. AT III 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 III. Conclusions: Our study suggests that AT III might be used as a therapeutic agent for allergic diseases.