Abstract
BackgroundBaicalein, a bioflavone present in the dry roots of Scutellaria baicalensis Georgi, is known to reduce eotaxin production in human fibroblasts. However, there are no reports of its anti-asthma activity or its effect on airway injury.Methodology/Principal FindingsIn a standard experimental asthma model, male Balb/c mice that were sensitized with ovalbumin (OVA), treated with baicalein (10 mg/kg, ip) or a vehicle control, either during (preventive use) or after OVA challenge (therapeutic use). In an alternate model, baicalein was administered to male Balb/c mice which were given either IL-4 or IL-13 intranasally. Features of asthma were determined by estimating airway hyperresponsiveness (AHR), histopathological changes and biochemical assays of key inflammatory molecules. Airway injury was determined with apoptotic assays, transmission electron microscopy and assessing key mitochondrial functions. Baicalein treatment reduced AHR and inflammation in both experimental models. TGF-β1, sub-epithelial fibrosis and goblet cell metaplasia, were also reduced. Furthermore, baicalein treatment significantly reduced 12/15-LOX activity, features of mitochondrial dysfunctions, and apoptosis of bronchial epithelia.Conclusion/SignificanceOur findings demonstrate that baicalein can attenuate important features of asthma, possibly through the reduction of airway injury and restoration of mitochondrial function.
Highlights
Asthma is associated with recruitment of various inflammatory cells such as eosinophils and lymphocytes to the airway
Earlier it was believed that airway inflammation plays the dominant role in asthma pathogenesis and airway epithelial injury was believed to be the downstream product of airway immune cell infiltration
Therapeutic strategies were focused on reducing airway inflammation
Summary
Asthma is associated with recruitment of various inflammatory cells such as eosinophils and lymphocytes to the airway. Repeated allergic inflammation leads to irreversible epithelial injury and causes the detachment of ciliated bronchial epithelial cells from the basement membrane. In support of this view, epithelial clumps have been found in sputum (creola bodies) and bronchoalveolar lavage (BAL) of asthmatic patients [2]. While inflammatory cells such as Th2 lymphocytes, eosinophils, and mast cells have historically occupied center stage in asthma research, recent reports have highlighted the critical role of epithelial stress in deciding the immune responses within the lung [3,4,5,6,7]. There are no reports of its anti-asthma activity or its effect on airway injury
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