College of Pharmacy, Youngnam University, Kyungsan 712-749, South Korea.
Exp Biol Med (Maywood). 2011 Feb;236(2):240-6. doi: 10.1258/ebm.2010.010274.
Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, allergic rhinitis, asthma and atopic dermatitis. The discovery of drugs for the treatment of allergic disease is an important subject in human health. In this study, we investigated the effect of Lindera obtusiloba water extract (LOWE) on the mast-cell-mediated allergic inflammation and possible mechanism of action using in vitro and in vivo models. LOWE reduced histamine release from various types of mast cells activated by immunoglobulin E (IgE) or phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI). The inhibitory effect of LOWE on histamine release was mediated by calcium signal. LOWE decreased the PMACI-stimulated gene expression of proinflammatory cytokines such as tumor necrosis factor-α and interleukin-6 in human mast cells. The inhibitory effect of LOWE on the proinflammatory cytokines was nuclear factor (NF)-κB dependent. In addition, LOWE suppressed compound 48/80-induced systemic allergic reaction and serum histamine release in mice and IgE-mediated local allergic reactions. Our results indicate that LOWE inhibits mast-cell-derived allergic inflammation and involvement of calcium, histamine, proinflammatory cytokines and NF-κB in these effects.
变应性疾病是暴露于通常无害的物质引起肥大细胞激活的结果。肥大细胞介导的过敏反应涉及许多疾病，如过敏反应、过敏性鼻炎、哮喘和特应性皮炎。治疗过敏疾病的药物的发现是人类健康的一个重要课题。在这项研究中，我们使用体外和体内模型研究了钝叶桂水提取物（LOWE）对肥大细胞介导的过敏炎症的作用及其可能的作用机制。LOWE 降低了免疫球蛋白 E（IgE）或佛波醇 12-肉豆蔻酸 13-乙酸酯和钙离子载体 A23187（PMACI）激活的各种类型肥大细胞释放的组胺。LOWE 对组胺释放的抑制作用是通过钙信号介导的。LOWE 降低了 PMACI 刺激的人肥大细胞中促炎细胞因子如肿瘤坏死因子-α和白细胞介素-6 的基因表达。LOWE 对促炎细胞因子的抑制作用依赖于核因子（NF）-κB。此外，LOWE 抑制了化合物 48/80 诱导的小鼠全身性过敏反应和血清组胺释放以及 IgE 介导的局部过敏反应。我们的结果表明，LOWE 抑制肥大细胞来源的过敏炎症，以及钙、组胺、促炎细胞因子和 NF-κB 参与这些作用。
