Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
J Ethnopharmacol. 2013 Jan 9;145(1):278-85. doi: 10.1016/j.jep.2012.11.004. Epub 2012 Nov 10.
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.
AT Ш，一种倍半萜烯，是白术的主要成分之一，已被用作传统的东方药物。
我们研究了 AT Ш 的抗过敏活性及其作用机制。
测量肥大细胞中β-己糖胺酶的释放量，这是脱颗粒的关键参数。通过体内被动皮肤过敏反应评估 AT Ш 的抗过敏潜力。通过免疫印迹分析、RT-PCR 和肥大细胞中[Ca(2+)]i 的测量研究 AT Ш 的抗过敏机制。
AT Ш 显著抑制 IgE/Ag 介导的 RBL-2H3 细胞脱颗粒，IC(50)值为 36 ± 4 μM，而不影响细胞活力。它还抑制 IgE/Ag 介导的被动皮肤过敏反应 (PCA) 反应，体内 ED(50)值为 65 ± 41 mg/kg。AT Ш 抑制白细胞介素 (IL-4) 和肿瘤坏死因子 (TNF)-alpha mRNA 的产生比 Src 家族激酶抑制剂 PP2 在所有浓度下更有效。为了阐明 AT Ш 在肥大细胞中的抗过敏机制，我们检查了信号分子的激活水平。AT Ш 抑制 Lyn、Fyn、Syk、LAT、PLCγ、Gab2、Akt、p38 和 JNK 激酶表达的磷酸化。AT Ш 显著抑制 IgE/Ag 介导的[Ca(2+)]i 升高。
我们的研究表明，AT Ш 可作为治疗过敏疾病的药物。
