Abstract

 
 
 
 Purpose: To investigate the protective effect of oroxylin A against neonatal asthma in mice.
 Methods: Asthma was induced in P12 mice with ovalbumin (OVA) immediately after litter (day 0), and on day 14 of protocol. Oroxylin A was given daily in two doses (2 and 10 mg/kg, i.p.) from day 0 to 14, 2 h before the administration of OVA. The protective effect of oroxylin A against asthma was determined by evaluating lung function and levels of cytokines and IgE in OVA-challenged mice. Moreover, Western blot assay and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the effect of oroxylin A on Notch signaling pathway in OVA-challenged mice.
 Results: Oroxylin A improved lung function in OVA-challenged mice. There were significant (p < 0.01) reductions in levels of IgE and cytokines in the BALF of oroxylin A-treated group, when compared to OVA group of mice. Furthermore, treatment with oroxylin A significantly ameliorated the OVA-induced changes in protein expressions of Notch1, Jagged1, NICD, PTEN, PI3K and Akt in the CD+ cells of OVA-challenged mice (p < 0.01).
 Conclusion: These results indicate that oroxylin A improves lung function and reduces the level of cytokines in neonatal asthmatic rat by downregulating Notch signaling. Thus, oroxylin A may be clinically beneficial in the management of asthma.
 
 
 
Highlights
Asthma is an inflammatory disorder of the respiratory system due to hyper-responsiveness and mucus secretion which lead to narrowing of the airways [1]
Percentage of airway resistance was enhanced with increase in the concentration of Oroxylin A reduced the levels of cytokines
Oroxylin A treatment markedly reduced the levels of IL-4, IL-5, IL-13 and IL-17, and increased the level of IFN-g in the Bronchoalveolar lavage fluid (BALF), when compared with the OVA group of mice
Summary
Asthma is an inflammatory disorder of the respiratory system due to hyper-responsiveness and mucus secretion which lead to narrowing of the airways [1]. Mast cells release inflammatory mediators due to accentuated production of IgE by the Th2 cytokines [3]. Asthma can be assessed by determining the stability of Th1/Th2 cytokine [4]. The present study determined the protective effect of oroxylin A against asthma in neonatal mice. Postnatal day 12 (P12) pups were used in the investigation, and OVA (20 mg) was administered i.p. with 4 mg of Al(OH) on days 0 and 14. The pups were further exposed to 1 % OVA from the 22nd day to the 24th day for the duration of 30 min. Buxco’s modular and invasive system was used to estimate airway hyper-responsiveness by exposing the animals to different concentrations of methacholine. The levels of the cytokines IFN-g, IL-4, IL-5, IL-6 and IL-17 in the BALF ELISA were determined using ELISA kits as per the instructions of the kit manufacturers
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