Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
Phytomedicine. 2013 Jul 15;20(10):853-60. doi: 10.1016/j.phymed.2013.03.012. Epub 2013 Apr 28.
Allergy is an acquired hypersensitivity reaction of the immune system mediated by cross-linking of the allergen-specific IgE-bound high-affinity IgE receptors, leading to immediate mast cell degranulation. Rottlerin is an active molecule isolated from Mallotus philippinensis, a medicinal plant used in Ayurvedic Medicine System for anti-allergic and anti-helminthic treatments. The present study investigated potential anti-allergic effects of rottlerin in animal models of IgE-dependent anaphylaxis and the anti-allergic mechanisms of action of rottlerin in mast cells. Anti-allergic actions of rottlerin were evaluated in passive cutaneous anaphylaxis and passive systemic anaphylaxis mouse models, and in anaphylactic contraction of bronchial rings isolated from sensitized guinea pigs. Direct mast cell-stabilizing effect of rottlerin was examined in RBL-2H3 mast cell line. Anti-allergic signaling mechanisms of action of rottlerin in mast cells were also examined. Rottlerin prevented IgE-mediated cutaneous vascular extravasation, hypothermia, elevation in plasma histamine level and tracheal tissue mast cell degranulation in mice in a dose-dependent manner. In addition, rottlerin suppressed ovalbumin-induced guinea pig bronchial smooth muscle contraction. Furthermore, rottlerin concentration-dependently blocked IgE-mediated immediate release of β-hexosaminidase from RBL-2H3 mast cells. Rottlerin was found to inhibit IgE-induced PLCγ1 and Akt phosphorylation, production of IP3 and rise in cytosolic Ca²⁺ level in mast cells. We report here for the first time that rottlerin possesses anti-allergic activity by blocking IgE-induced mast cell degranulation, providing a foundation for developing rottlerin for the treatment of allergic asthma and other mast cell-mediated allergic disorders.
过敏是一种由过敏原特异性 IgE 结合的高亲和力 IgE 受体交联介导的获得性超敏反应，导致即刻肥大细胞脱颗粒。罗特林是从锦葵科植物马鲁特氏木中分离出来的一种活性分子，该植物在印度阿育吠陀医学系统中用于治疗过敏和驱虫。本研究在 IgE 依赖性过敏反应的动物模型中研究了罗特林的潜在抗过敏作用，以及罗特林在肥大细胞中的抗过敏作用机制。在被动皮肤过敏和被动全身过敏小鼠模型中，以及在致敏豚鼠支气管环的过敏收缩中评估了罗特林的抗过敏作用。在 RBL-2H3 肥大细胞系中检查了罗特林对肥大细胞的直接稳定作用。还研究了罗特林在肥大细胞中的抗过敏信号转导机制。罗特林以剂量依赖的方式预防 IgE 介导的皮肤血管外渗、体温降低、血浆组氨酸水平升高和小鼠气管组织肥大细胞脱颗粒。此外，罗特林抑制卵清蛋白诱导的豚鼠支气管平滑肌收缩。此外，罗特林浓度依赖性地阻断 IgE 介导的 RBL-2H3 肥大细胞β-己糖胺酶的即刻释放。罗特林被发现可抑制 IgE 诱导的 PLCγ1 和 Akt 磷酸化、IP3 的产生和细胞内钙²⁺水平的升高。我们在这里首次报道罗特林具有通过阻断 IgE 诱导的肥大细胞脱颗粒来抑制过敏的活性，为开发罗特林治疗过敏性哮喘和其他肥大细胞介导的过敏疾病提供了依据。
