Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation |
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Authors: | Lu Yue Yang Ju Hye Li Xian Hwangbo Kyoung Hwang Seung-Lark Taketomi Yoshitaka Murakami Makoto Chang Young-Chae Kim Cheorl-Ho Son Jong-Keun Chang Hyeun Wook |
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Affiliation: | aCollege of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea;bLipid Metabolism Project, The Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa, Setagaya-ku, Tokyo 156-8506, Japan;cDepartment of Pathology, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea;dDepartment of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea |
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Abstract: | The high-affinity receptor for IgE (Fc?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 D2 and leukotriene C4), and secretion of cytokines (TNF-α and IL-6) in a dose-dependent manner in IgE/Ag-stimulated mast cells. Biochemical analysis of the Fc?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-κB 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. |
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Keywords: | Abbreviations: BMMC, bone marrow-derived mast cell Syk, spleen tyrosine kinase LAT, linker of activated T cells PLCγ1, phospholipase Cγ1 cPLA2α, cytosolic phospholpase A2α COX-2, cyclooxygenase-2 5-LO, 5-lipoxygenase PCA, passive cutaneous anaphylaxis |
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