Department of Health Sciences, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa 903-0215, Japan.
Int Immunopharmacol. 2012 Apr;12(4):675-81. doi: 10.1016/j.intimp.2012.01.013. Epub 2012 Feb 11.
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 IC(50) values for degranulation of rat basophilic leukemia cells (RBL-2H3) were 14 nM for OCS and 3 μM 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 (Ca(2+)) elevation was significantly inhibited by OCS and aglycon at all concentrations tested (p<0.05). Upstream of the Ca(2+) elevation in the principle signaling pathway, phosphorylation of Syk (Tyr525/526) and PLCγ-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.
植物中的脱粒抑制剂被广泛用于预防和治疗Ⅰ型过敏。我们之前从山茶属植物的叶子中分离出一种新的鞣花酸葡萄糖苷——奥卡米莲糖苷（OCS），将其作为一种有效的脱粒抑制剂。叶子的粗提取物也抑制了大鼠过敏性结膜炎。在这项研究中，我们使用纯样品评估了 OCS 的体内作用，并进行了体外实验，以阐明 OCS 及其苷元非凡高活性的机制。OCS 和苷元对大鼠嗜碱性白血病细胞（RBL-2H3）脱粒的 IC50 值分别为 14 nM 和 3 μM，表明这两种化合物的效力比抗过敏药物富马酸酮替芬、地塞米松和曲尼司特分别高出 2 到 3 个数量级（分别为 0.17、3 和>0.3 mM）。OCS 和苷元在所有测试浓度下均显著抑制抗原诱导的钙离子（Ca2+）升高（p<0.05）。在主要信号通路中，Ca2+升高的上游，OCS 和苷元抑制了 Syk（Tyr525/526）和 PLCγ-1（Tyr783 和 Ser1248）的磷酸化。在 DNA 微阵列筛选测试中，OCS 抑制了促炎细胞因子[白细胞介素（IL）-4 和 IL-13]、细胞因子产生信号因子和前列腺素内过氧化物酶 2 的表达，表明 OCS 广泛抑制过敏炎症。在小鼠被动皮肤过敏反应中，OCS 通过两种给药途径显著抑制血管通透性增加：单次腹腔注射 10 mg/kg 和口服 5 mg/kg 连续 7 天（p<0.05）。这些结果表明 OCS 有可能缓解Ⅰ型过敏的症状。
