Ram Arjun, Mabalirajan U, Das Moumita, Bhattacharya Indranil, Dinda Amit K, Gangal Sharad V, Ghosh Balaram
Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.
Int Immunopharmacol. 2006 Sep;6(9):1468-77. doi: 10.1016/j.intimp.2006.04.020. Epub 2006 Jun 6.
Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.
哮喘是一种慢性呼吸道疾病,其发病率在全球范围内呈上升趋势。现有的治疗方法并不充分,且有许多不良反应。因此需要一种更好的治疗分子,最好是天然来源的,其不良反应可忽略不计或没有不良反应。鉴于此,我们评估了光果甘草的主要成分甘草甜素(GRZ)对哮喘小鼠模型哮喘特征的疗效。用卵清蛋白(OVA)对BALB/c小鼠进行致敏和激发,以诱发哮喘特征,如气道高反应性:变应原诱导的气道收缩和对乙酰甲胆碱(MCh)的气道高反应性(AHR),以及肺部炎症。在OVA致敏期间或之后以及OVA激发后,分别用GRZ(2.5、5、10和20mg/kg)对小鼠进行口服治疗,以评估其对上述哮喘特征的保护或逆转作用。通过使用非侵入性方法监测比气道传导率(SGaw)来测量气道高反应性状态,并通过对肺切片进行苏木精和伊红染色来评估肺部炎症。通过酶联免疫吸附测定法测量与哮喘相关的其他几个参数,如白细胞介素(IL)-4、IL-5、干扰素-γ(IFN-γ)、OVA特异性IgE、总IgG(2a)和皮质醇。GRZ(5mg/kg)显著抑制OVA诱导的即刻气道收缩、对MCh的AHR(p<0.01)、肺部炎症以及支气管周围和血管周围区域嗜酸性粒细胞的浸润。它可防止IFN-γ的降低(p<0.02),并降低BAL液中的IL-4(p<0.05)、IL-5(p<0.05)和嗜酸性粒细胞(p<0.0002)。此外,它降低了血清中OVA特异性IgE水平(p<0.01),并防止了总IgG(2a)的降低(p<0.01)。我们还表明它对血清皮质醇水平没有影响。我们的结果表明,GRZ可减轻小鼠的哮喘特征,并且在未来开发更好的治疗分子方面可能会有用。