Abstract
Purpose: To examine the anti-asthmatic activity of picroside I in murine asthma model, and to elucidate the mechanism(s) involved. Methods: The study involved systematic sensitization of acclimatized BALB/c mice with ovalbumin (OVA), and subsequent exposure to aerosol allergens. The effect of picroside I on associated IgE formation was determined. All assays were performed using standard protocols. Protein expression was assessed using western blotting. Results: Picroside I inhibited allergic airway inflammation, AHR, and the production of OVA-associated IgE and Th2 cytokines. Moreover, it altered the T-bet/GATA3 ratio by suppressing the phosphorylation of STAT6 in a dose-dependent manner. Conclusion: These results indicate that the anti-asthmatic effect of picroside I occurs via a mechanism involving inhibition of Th2 cytokines by suppression of the expressions of pSTAT6 and GATA-3, and upregulation of the expression of T-bet. Thus, picroside I is a promising agent for the management of asthma. Keywords: Picroside, Asthma, Allergic response, IgE, GATA-3, pSTAT6
Highlights
Asthma is considered one of the main chronic inflammatory airway diseases
Assessment of the picroside I on airway hyperresponsiveness (AHR) revealed no significant differences in the baseline airway resistance among the six groups
The expressions of pSTAT6, GATA-3 and T-bet in lung tissue homogenates were determined in control, OVA control, DEXA-administrated, and picroside I-treated mice
Summary
Asthma is considered one of the main chronic inflammatory airway diseases. It impacts over three hundred million people the world over, and is expected to affect another hundred million by 2025 [1]. The allergens processed by antigen-presenting cells trigger the initiation of Th2 cells and release of various cytokines These cytokines intensify the allergic response by enhancing inflammatory cell infiltration into the airways, and by initiating disproportionate formation of mucus [6]. For sensitization of the mice, 40 μg of OVA plus 2.6 mg of Al(OH) in PBS (200 μL) were given intraperitoneally on days 0 and 7. The measurement of AHR was carried out as Figure 1: Procedure used for triggering allergic asthma in the mice Trop J Pharm Res, September 2018; 17(9): 1778 described previously [9]. Mice administered picroside I at concentrations of 0.2, 2 and 20 mg/kg exhibited no remarkable changes in these cytokines relative to control group. Values of p < 0.05 were considered as indicator of significant difference
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