Lee Seung-Ho, Seo Mi Jung, Choi Seul Min, Sohn Yong Sung, Kang Kyung Koo, Ahn Byoung Ok, Kwon Jong Won, Yoo Moohi
Research Institutes of Dong-A Pharmaceutical Company, Yongin, Korea.
Arch Pharm Res. 2005 Dec;28(12):1350-7. doi: 10.1007/BF02977901.
Nuclear factor kappa B (NF-kappaB) regulates the expression of multiple cytokines, chemokines, and cell adhesion molecules that are involved in the pathogenesis of asthma. We investigated the anti-asthmatic effects and the mechanism of action of DA-9201, an extract of the black rice, in a mouse model of asthma. Mice immunized with ovalbumin (OVA) were administered with DA-9201 (30, 100 or 300 mg/kg) or dexamethasone (DEXA, 3 mg/kg) for 2 weeks and challenged with aerosolized OVA during the last 3 days. Anti-asthmatic effects were assessed by means of enhanced pauses, level of total IgE and Th2 cytokines in plasma or bronchoalveolar lavage fluid (BALF), the percentage of eosinophils in BALF, and histopathological examination. The expression of NF-kappaB in nuclear and cytoplasmic fraction and its DNA-binding activity in lung tissues were analyzed by means of Western blotting and electrophoretic gel mobility shift assay (EMSA), respectively. DA-9201 significantly reduced airway hyperresponsiveness (AHR), total IgE level in plasma and BALF, IL-4, IL-5, and IL-13 levels in BALF, and the percentage of eosinophils in BALF. Tissue inflammation was significantly improved by DA-9201 treatment. In addition, DA-9201 dramatically suppressed the expression of NF-kappaB and its DNA-binding activity. These results suggest that DA-9201 may be useful for the treatment of asthma and its efficacy is related to suppression of NF-kappaB pathway.
核因子κB(NF-κB)调节多种细胞因子、趋化因子和细胞黏附分子的表达,这些分子参与哮喘的发病机制。我们在哮喘小鼠模型中研究了黑米提取物DA-9201的抗哮喘作用及其作用机制。用卵清蛋白(OVA)免疫的小鼠给予DA-9201(30、100或300mg/kg)或地塞米松(DEXA,3mg/kg),持续2周,并在最后3天用雾化OVA进行激发。通过增强呼吸暂停、血浆或支气管肺泡灌洗液(BALF)中总IgE和Th2细胞因子水平、BALF中嗜酸性粒细胞百分比以及组织病理学检查来评估抗哮喘作用。分别通过蛋白质免疫印迹法和电泳凝胶迁移率变动分析(EMSA)分析肺组织中核和细胞质部分NF-κB的表达及其DNA结合活性。DA-9201显著降低气道高反应性(AHR)、血浆和BALF中总IgE水平、BALF中IL-4、IL-5和IL-13水平以及BALF中嗜酸性粒细胞百分比。DA-9201治疗显著改善了组织炎症。此外,DA-9201显著抑制NF-κB的表达及其DNA结合活性。这些结果表明,DA-9201可能对哮喘治疗有用,其疗效与抑制NF-κB途径有关。