Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation
Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation
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DOI：
10.1016/j.bcp.2011.08.022
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发表时间：
2011-12-01
影响因子：
5.8
通讯作者：
Chang, Hyeun Wook
中科院分区：
文献类型：
--
作者：
Lu, Yue;Yang, Ju Hye;Chang, Hyeun Wook
高亲和力IgE受体（Fc ε RI）介导的肥大细胞活化在过敏性疾病如哮喘、过敏性鼻炎和特应性皮炎中起重要作用。大黄素是一种天然存在于东方草药中的蒽醌衍生物，具有多种有益的药理作用，如抗癌和抗糖尿病活性。然而，大黄素的抗过敏作用尚未被研究。为探讨大黄素的抗过敏作用，采用体内被动过敏动物模型和体外培养小鼠骨髓源性肥大细胞，研究大黄素对肥大细胞的作用机制。我们的研究结果表明，大黄素抑制脱粒，产生类花生酸（前列腺素D-2和白三烯C-4），并分泌细胞因子（TNF-α和IL-6）在IgE/Ag刺激的肥大细胞中的剂量依赖性方式。对Fe epsilon RI介导的信号传导途径的生化分析表明，大黄素抑制Syk的磷酸化和多种下游信号传导过程，包括细胞内Ca 2+的动员和促分裂原活化蛋白激酶、磷脂酰肌醇3-激酶和NF-κ B途径的激活。口服大黄素可减轻IgE致敏小鼠的肥大细胞依赖性被动过敏反应。因此，大黄素通过抑制受体近端Syk依赖性信号通路抑制肥大细胞活化，从而抑制过敏反应。因此，大黄素可能为开发新的抗过敏药物提供基础。皇冠版权所有（C）2011由爱思唯尔公司出版。All rights reserved.
The high-affinity receptor for IgE (Fc epsilon RI)-mediated activation of mast cells plays an important role in allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. Emodin, a naturally occurring anthraquinone derivative in oriental herbal medicines, has several beneficial pharmacologic effects, such as anti-cancer and anti-diabetic activities. However, the anti-allergic effect of emodin has not yet been investigated. To assess the anti-allergic activity of emodin, in vivo passive anaphylaxis animal model and in vitro mouse bone marrow-derived mast cells were used to investigate the mechanism of its action on mast cells. Our results showed that emodin inhibited degranulation, generation of eicosanoids (prostaglandin D-2 and leukotriene C-4), and secretion of cytokines (TNF-alpha and IL-6) in a dose-dependent manner in IgE/Ag-stimulated mast cells. Biochemical analysis of the Fc epsilon RI-mediated signaling pathways demonstrated that emodin inhibited the phosphorylation of Syk and multiple downstream signaling processes including mobilization of intracellular Ca2+ and activation of the mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and NF-kappa B pathways. When administered orally, emodin attenuated the mast cell-dependent passive anaphylactic reaction in IgE-sensitized mice. Thus, emodin inhibits mast cell activation and thereby the anaphylactic reaction through suppression of the receptor-proximal Syk-dependent signaling pathways. Therefore, emodin might provide a basis for development of a novel anti-allergic drug. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.