Anti-malarial drug,artesunate,as a novel therapeutic drug target for airway wall remodeling in asthma

作     者：SherylTAN BenjaminONG ChangCHENG WanxingEugeneHO JohnK.CTAM AlastairG.STEWART TrudiHARRIS Wai-ShiuFredWONG ThaiTRAN 

作者机构：Department of Physiology Yong Loo Lin School of Medicine National University of Singapore Department of Pharmacology Yong Loo Lin School of Medicine National University of Singapore Saw Swee Hock School of Public Health National University Health System Singapore Department of Surgery Yong Loo Lin School of Medicine National University of Singapore Singapore Department of Pharmacology University of Melbourne Australia 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2015年第29卷第S1期

页      面：54-55页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

主　　题：asthma airway wall remodeling PI3K cyclin D1 

摘      要：OBJECTIVE Airway wall remodeling(AWR),which refers to structural changes in the airway,is a key characteristic of *** smooth muscle(ASM)cell hypertrophy and hyperplasia contributes to ***,which are used as first line therapy for the treatment of asthma,reduce ASM proliferation but the magnitude of their anti-proliferative actions is dependent on the mitogen ***,glucocorticoid therapy is accompanied by many side ***,a semi-synthetic artemisinin derivative,has been widely used to treat malaria with minimal *** has been shown to attenuate allergic airway inflammation in ***,its role in treating AWR in asthma is not *** this study,we hypothesize that artesunate has anti-proliferative actions on ASM cells,potentially reversing *** and RESULTS Quiescent primary human ASM cells were pre-treated(1h)with artesunate(3,10,30μmol·L-1)before being stimulated with either FBS(10%)or thrombin(0.3U·mL-1).Following 48 h stimulation with mitogen,cells were counted using a ***(Dex,100nmol·L-1)was used as a positive *** concentration-dependently reduced cell number and the magnitude of inhibition appeared to be non-mitogen ***,we examined the effect of artesunate on two important signalling proteins involved in cell proliferation,ERK1/2phosphorylation and cyclin D1 protein *** reduced cyclin D1 protein levels significantly following 20 h stimulation with either thrombin or FBS but had no effect on ERK1/2 phosphorylation following 6h ***,artesunate(30μmol·L-1),but not Dex,inhibited the phosphorylation of Akt,which is upstream of cyclin ***,we show that the inhibitory effect of artesunate,but not Dex,on ASM cell number is retained at least 24h post-treatment following stimulation with *** an acute murine model of allergic asthma,artesunate treatment decreased sm-α-actin positive cells and cyclin D1 protein