Inhaled Carbenoxolone Prevents Allergic Airway Inflammation and Airway Hyperreactivity in a Mouse Model of Asthma

Abstract

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.

Modulatory effect of anisodamine on airway hyper-reactivity and eosinophilic inflammation in a murine model of allergic asthma

“…We observed increasing numbers of eosinophils and the increased contractility of isolated bronchi in OVA-challenged mice, whereby the increase in the number of eosinophils showed a positive correlation to contractility (data not shown). Similar results have been reported by other investigators using different immunization protocols [18]. Glucocorticoids could attenuate airway eosinophilia by inducing eosinophil apoptosis and inhibiting IL-5-and granulocyte macrophage-colony-stimulating factor (GM-CSF)-induced eosinophil survival, which might be important in the treatment of allergic and other eosinophilic disorders [19,20].…”

IL-13-induced changes in endogenous glucocorticoid metabolism in the lung regulate the proasthmatic response

“…6B), an observation consistent with that in an earlier study demonstrating that that glycyrrhizin (another 11␤-HSD inhibitor) partially inhibits TNF-␣-and IL-4-induced eotaxin-1 production by human fetal lung fibroblasts (27). In this regard, it is important to consider that like glycyrrhizin and glycyrrhetinic acid, CBX was reported to also have intrinsic anti-inflammatory properties (23,39). Accordingly, these properties may have contributed to our observed tendency for CBX alone to inhibit eotaxin-3 production, and the observed in vivo anti-inflammatory effects of CBX in the IL-13-exposed rabbit lung (Fig.…”

Parabromophenacyl Bromide Inhibits Subepithelial Fibrosis by Reducing TGF-β₁ in a Chronic Mouse Model of Allergic Asthma

“…On day 110, AHR was estimated in all mice as described earlier [16], followed by euthanasia to collect bronchoalveolar lavage fluid, blood and lung samples [17,18]. Blood was centrifuged at 1,000 g for 30 min to collect sera.…”