title: Evaluation of pharmacological relaxation effect of the natural product naringin onin vitrocultured airway smooth muscle cells andin vivoovalbumin-induced asthma Balb/c mice.
abstract: Asthma has become a common chronic respiratory disease worldwide and its prevalence is predicted to continue increasing in the next decade, particularly in developing countries. A key component in asthma therapy is to alleviate the excessive bronchial airway narrowing ultimately due to airway smooth muscle contraction, which is often facilitated by a smooth muscle relaxant, such as the β2-adrenergic agonists. Recently, bitter taste receptor (TAS2R) agonists, including saccharin and chloroquine, have been found to potently relax the airway smooth muscle cells (ASMCs) via intracellular Ca2+signaling. This inspires a great interest in screening the vast resource of natural bitter substances for potential bronchodilatory drugs. In the present study, the relaxation effect of naringin, a compound extracted from common grapefruit, on ASMCs culturedin vitroor bronchial airways of Balb/c micein vivowas evaluated. The results demonstrated that, when exposed to increasing doses of naringin (0.125, 0.25, 0.5 and 1.0 mM), the traction force generated by the cultured ASMCs decreased progressively, while the intracellular calcium flux signaling in the ASMCs increased. When inhaled at increasing doses (15, 30 and 60 µg), naringin also dose-dependently reduced the bronchial airway resistance of the normal and ovalbumin-induced asthma Balb/c mice in response to challenge with methacholine. In conclusion, these findings indicate that naringin was able to effectively relax murine ASMCsin vitroandin vivo, thus suggesting that it is a promising drug agent to be further investigated in the development of novel bronchodilators for the treatment of asthma.
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Nursing, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Luo
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Xiaohao
authors.initials: X
authors.lastname: Shi
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Huilong
authors.initials: H
authors.lastname: Zeng
authors.affiliation: Changzhou Key Laboratory of Respiratory Medical Engineering, Institute of Biomedical Engineering and Health Sciences, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Nursing, Changzhou University, Changzhou, Jiangsu 213164, P.R. China; School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, P.R. China.
authors.forename: Linhong
authors.initials: L
authors.lastname: Deng
keywords: airway smooth muscle relaxation; asthma therapy; bitter taste receptor agonist; bronchial resistance; cell traction force; naringin