Inhaled carbenoxolone prevents allergic airway inflammation and airway hyperreactivity in a mouse model of asthma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Inhaled CBX alleviates the asthmatic features in mice and could be a potent nebulized therapy in clinical asthma.
Ram
Arjun
A
Institute of Genomics and Integrative Biology, Delhi University Campus, India. aram@igib.res.in
Singh
Shashi Kant
SK
Singh
Vijay Pal
VP
Kumar
Sarvesh
S
Ghosh
Balaram
B
D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000276:immunology / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002229:Carbenoxolone / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009330:Nebulizers and Vaporizers; D010047:Ovalbumin / Q000276:immunology
D007073:Immunoglobulin E; D010047:Ovalbumin; D002229:Carbenoxolone