Akademik Veri Yönetim Sistemi
World Immune Regulation Meeting XVII 2023, Zürich, İsviçre, 5 - 08 Temmuz 2023, cilt.17, ss.65-66
Asthma is an inflammatory disease characterized by airway inflammation, airway hyperreactivity (AHR), and remodeling. Although inhaled corticosteroids are used for asthmatic patients, side effects of current drugs and therapy unresponsiveness influence morbidity, mortality, and quality of life. Cycloastragenol (CAG) has been reported to alleviate airway inflammation in a mouse model of asthma. However, its specific mechanisms remain unclear. The aim of the present study is to investigate the effects of CAG on asthma and elucidate the mechanism of CAG's regulation. Here, we confirmed the effects of CAG and its mechanisms on a house dust mite (HDM)-induced mouse model of asthma and air-liquid interface (ALI) cultures. The mice were sensitized on day 0 by 10 ug HDM extract and then challenged from day 7 to 11 by 20 ug HDM. 125 mg/kg CAG was given before the challenge for a 5-day treatment. We verified the therapeutic effect of CAG in the asthmatic mice model by evaluating airway inflammation, AHR, and mucus secretion. Furthermore, the ALI cultures of primary human bronchial cells were treated with CAG at 0.11 uM and 0.03 uM doses in the presence or absence of HDM for 3 days. We measured the transepithelial electrical resistance (TEER) every day and fluorescein isothiocyanate (FITC)-dextran permeability after 72 hours. Results showed that 125mg/kg CAG prevented HDM-induced asthmatic mice from AHR, airway inflammation, and mucus hypersecretion. With exposure to HDM, the relative TEER was significantly decreased while 0.03 uM CAG had the tendency to revert it in ALI cultures. Moreover, HDM caused an increase in the paracellular flux whereas 0.03 uM CAG reverted the HDM-induced increase of the permeability of the airway epithelial barrier. In summary, CAG exerts protective effects against asthma-like inflammation development through alleviating airway inflammation and mucus hypersecretion and rescues bronchial epithelial barrier impairment caused by HDM in vitro.