Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
High-Enthalpy Plasma Research Center, Chonbuk National University, Republic of Korea.
Life Sci. 2014 Mar 11;98(2):103-12. doi: 10.1016/j.lfs.2014.01.003. Epub 2014 Jan 18.
The (2'S,7'S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR).
We assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models.
OMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels.
OMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR.
（2'S，7'S）-O-（2-甲基丁酰基）-哥伦比亚亭（OMC）是一种从紫堇属异紫堇中提取的新型次生代谢产物，长期以来一直被用作韩国治疗各种炎症性疾病的民间药物。我们研究了 OMC 对过敏性鼻炎（AR）的影响。
我们评估了 OMC 对佛波醇 12-肉豆蔻酸 13-乙酸酯加 A23187 刺激的肥大细胞系 HMC-1 细胞和卵清蛋白（OVA）诱导的 AR 模型的治疗效果和调节机制。
OMC 可显著减少受刺激的 HMC-1 细胞中组胺和胰蛋白酶的释放。脱颗粒过程表现为表面和质膜皱襞上丝状伪足的形态延伸，在受刺激的 HMC-1 细胞中强烈诱导，然而 OMC 抑制了受刺激的 HMC-1 细胞的形态变化。OMC 降低了炎症细胞因子的产生和 mRNA 表达。这些由 OMC 引起的抑制作用依赖于丝裂原激活的蛋白激酶、核因子-κB 和半胱天冬酶-1 信号通路的调节。在 AR 动物模型中，OMC 可减少卵清蛋白（OVA）致敏小鼠的鼻评分和 AR 生物标志物（组胺和 IgE）的增加。此外，通过调节巨噬细胞炎症蛋白和细胞间黏附分子-1 的水平，也阻止了鼻黏膜组织中嗜酸性粒细胞和肥大细胞的浸润。
OMC 显示了在激活的肥大细胞和 OVA 诱导的 AR 模型中调节 AR 的可能性。因此，我们认为 OMC 是一种强大且可行的抑制 AR 的新药物。
