Abstract
Chronic obstructive pulmonary disease (COPD) is a chronic lung disease with limited therapeutic options. Ephedrine (Eph) isolated from Ephedra exerts regulatory role in inflammatory response. However, its effects on COPD development still remain unknown. In the present study, we found that Eph significantly ameliorated apoptosis, oxidative stress and inflammatory response in cigarette smoke extract (CSE)-stimulated human bronchial epithelial cells (HBECs). Moreover, all these cellular events attenuated by Eph were closely associated with reactive oxygen species (ROS) decreasing. Furthermore, we found that the expression of endoplasmic reticulum (ER) stress-associated signaling could be down-regulated by Eph in HBECs without any stimuli. Meanwhile, ER stress was strongly induced by CSE, which was, however, effectively mitigated by Eph exposure in HBECs. Intriguingly, we found that Eph-alleviated cell death, ROS generation and inflammation were almost eliminated by the promotion of ER stress via over-expressing Bip in HBECs upon CSE stimulation. Moreover, Eph administration significantly ameliorated pulmonary indexes and histological impairments in mice with long-term CS exposure, which were largely through the suppression of inflammation, apoptosis and oxidative stress via blocking ER stress as detected in vitro. Collectively, all these findings indicated that Eph exhibited protective effects against CS-caused COPD by hindering ER stress.