Inhibitory effects of an ellagic acid glucoside, okicamelliaside, on antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells and passive cutaneous anaphylaxis reaction in mice

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• 作者：Megumi Kuba-Miyara^a ; ^{kubame93@med.u-ryukyu.ac.jp} ; Kengo Agarie^a ; Rina Sakima^b ; Shihoko Imamura^b ; Kazuyo Tsuha^b ; Takeshi Yasumoto^b ; Shinichi Gima^c ; Goro Matsuzaki^d ; Tsuyoshi Ikehara^b ; ^{tikehara@ttc.co.jp}
• 关键词：Allergy ; Degranulation ; Ellagic acid glucoside ; Okicamelliaside ; Passive cutaneous anaphylaxis ; RBL-2H3
• 刊名：International Immunopharmacology
• 出版年：2012
• 期刊代码：123_15675769
• 类别：med
• 出版时间：April, 2012
• 卷：12
• 期：4
• 页码：675-681
• 文件大小：727 K

摘要

Degranulation inhibitors in plants are widely used for prevention and treatment of immediate-type allergy. We previously isolated a new ellagic acid glucoside, okicamelliaside (OCS), from Camellia japonica leaves for use as a potent degranulation inhibitor. Crude extracts from leaves also suppressed allergic conjunctivitis in rats. In this study, we evaluated the in vivo effect of OCS using a pure sample and performed in vitro experiments to elucidate the mechanism underlying the extraordinary high potency of OCS and its aglycon. The IC₅₀ values for degranulation of rat basophilic leukemia cells (RBL-2H3) were 14 nM for OCS and 3 渭M for aglycon, indicating that the two compounds were approximately 2 to 3 orders of magnitude more potent than the anti-allergic drugs ketotifen fumarate, DSCG, and tranilast (0.17, 3, and > 0.3 mM, respectively). Antigen-induced calcium ion (Ca²⁺) elevation was significantly inhibited by OCS and aglycon at all concentrations tested (p < 0.05). Upstream of the Ca²⁺ elevation in the principle signaling pathway, phosphorylation of Syk (Tyr525/526) and PLC纬-1 (Tyr783 and Ser1248) were inhibited by OCS and aglycon. In DNA microarray-screening test, OCS inhibited expression of proinflammatory cytokines [interleukin (IL)-4 and IL-13], cytokine-producing signaling factors, and prostaglandin-endoperoxidase 2, indicating that OCS broadly inhibits allergic inflammation. During passive cutaneous anaphylaxis in mice, OCS significantly inhibited vascular hyperpermeability by two administration routes: a single intraperitoneal injection at 10 mg/kg and per os at 5 mg/kg for 7 days (p < 0.05). These results suggest the potential for OCS to alleviate symptoms of immediate-type allergy.