Emodin, a naturally occurring anthraquinone derivative, suppresses IgE-mediated anaphylactic reaction and mast cell activation.

Abstract

The high-affinity receptor for IgE (FcɛRI)-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-α and IL-6) in a dose-dependent manner in IgE/Ag-stimulated mast cells. Biochemical analysis of the FcɛRI-mediated signaling pathways demonstrated that emodin inhibited the phosphorylation of Syk and multiple downstream signaling processes including mobilization of intracellular Ca(2+) 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.

• Authors: Yue Lu, Ju Hye Yang, Xian Li, Kyoung Hwangbo, Seung-Lark Hwang, Yoshitaka Taketomi, Makoto Murakami, Young-Chae Chang, Cheorl-Ho Kim, Jong-Keun Son, Hyeun Wook Chang
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 82 Issue 11 Pg. 1700-8 (Dec 01 2011) ISSN: 1873-2968 [Electronic] England
• PMID: 21907188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Allergic Agents
• Interleukin-6
• Intracellular Signaling Peptides and Proteins
• Tumor Necrosis Factor-alpha
• Leukotriene C4
• Immunoglobulin E
• Protein-Tyrosine Kinases
• Syk Kinase
• Syk protein, mouse
• Emodin
• Prostaglandin D2
• Calcium

Topics

• Anaphylaxis (immunology, metabolism, prevention & control)
• Animals
• Anti-Allergic Agents (pharmacology, therapeutic use)
• Calcium (metabolism)
• Cell Degranulation (drug effects)
• Cells, Cultured
• Emodin (pharmacology, therapeutic use)
• Enzyme Activation
• Immunoglobulin E (immunology)
• Interleukin-6 (biosynthesis)
• Intracellular Signaling Peptides and Proteins (metabolism)
• Leukotriene C4 (biosynthesis)
• Male
• Mast Cells (drug effects, immunology, physiology)
• Mice
• Mice, Inbred BALB C
• Passive Cutaneous Anaphylaxis
• Prostaglandin D2 (biosynthesis)
• Protein-Tyrosine Kinases (metabolism)
• Syk Kinase
• Tumor Necrosis Factor-alpha (biosynthesis)