Ram Arjun, Singh Shashi Kant, Singh Vijay Pal, Kumar Sarvesh, Ghosh Balaram
Institute of Genomics and Integrative Biology, Delhi University Campus, India.
Int Arch Allergy Immunol. 2009;149(1):38-46. doi: 10.1159/000176305. Epub 2008 Nov 26.
Asthma is a chronic respiratory disease, which needs a safer medication preferably in inhalation form. In view of this, we have evaluated the effect of inhaled carbenoxolone (CBX), a herbal-derived compound, on asthma in a mouse model.
Mice were sensitized and challenged with ovalbumin (OVA) to develop certain characteristic features of asthma such as airway hyperreactivity (AHR), airway eosinophilia, lung inflammation and mucus hypersecretion. To evaluate the effect of CBX on the above asthmatic features, CBX (2.5, 5 and 10 mg/ml, 3 ml) or vehicle (water) was given by inhalation. AHR was determined using whole-body plethysmography. Infiltration of eosinophils was estimated by microscopy. Lung inflammation and mucus hypersecretion were assessed using hematoxylin and eosin, and periodic acid-Schiff staining, respectively. Th-2 cytokines, IL-4 and IL-5 were measured in bronchoalveolar lavage (BAL) fluid and IgE in sera. To identify the possible mode of CBX action, we measured corticosterone levels in the BAL fluid and 5-lipoxygenase (5-LO) expression in the lungs.
CBX (5 mg/ml) inhalation markedly alleviated AHR (p = 0.0032) and reduced lung inflammation and mucus hypersecretion. Also, it prevented the increase in IL-4 (p = 0.0192), IL-5 (p = 0.0116) and eosinophils (p < 0.0005) in the BAL fluid, and OVA-specific IgE levels (p = 0.00061) in sera. 5-LO expression was also markedly reduced. However, corticosterone levels were not affected.
Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma.
哮喘是一种慢性呼吸道疾病,需要一种更安全的药物,最好是吸入剂型。鉴于此,我们在小鼠模型中评估了吸入性甘草次酸(CBX)(一种植物来源的化合物)对哮喘的影响。
用卵清蛋白(OVA)对小鼠进行致敏和激发,以产生哮喘的某些特征,如气道高反应性(AHR)、气道嗜酸性粒细胞增多、肺部炎症和黏液分泌过多。为了评估CBX对上述哮喘特征的影响,通过吸入给予CBX(2.5、5和10mg/ml,3ml)或赋形剂(水)。使用全身体积描记法测定AHR。通过显微镜估计嗜酸性粒细胞的浸润情况。分别使用苏木精和伊红染色以及过碘酸-希夫染色评估肺部炎症和黏液分泌过多情况。在支气管肺泡灌洗(BAL)液中测量Th-2细胞因子白细胞介素-4(IL-4)和白细胞介素-5,并在血清中测量免疫球蛋白E(IgE)。为了确定CBX可能的作用方式,我们测量了BAL液中的皮质酮水平以及肺中5-脂氧合酶(5-LO)的表达。
吸入CBX(5mg/ml)显著减轻了AHR(p = 0.0032),并减少了肺部炎症和黏液分泌过多。此外,它还阻止了BAL液中IL-4(p = 0.0192)、IL-5(p = 0.0116)和嗜酸性粒细胞(p < 0.0005)的增加,以及血清中OVA特异性IgE水平(p = 0.00061)的增加。5-LO的表达也显著降低。然而,皮质酮水平未受影响。
吸入CBX可减轻小鼠的哮喘特征,可能是临床哮喘的一种有效的雾化治疗方法。