期刊
BIOCHEMICAL PHARMACOLOGY
卷 82, 期 11, 页码 1700-1708出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2011.08.022
关键词
Emodin; Passive anaphylactic reaction; Mast cells; IgE; Syk kinase
资金
- National Research Foundation of Korea (NRF) [NRF-2010-616-E00011]
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- JSPS-NRF [FY2010]
- Fisheries Technology Development Program
- Ministry for Food, Agriculture, Forestry and Fisheries of Korean Government
- Institute of Planning & Evaluation for Technology in Food, Agriculture, Forestry & Fisheries (iPET), Republic of Korea [IPET110079-3] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- Grants-in-Aid for Scientific Research [23790119] Funding Source: KAKEN
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.
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