Li Lin1, Yan Yin1, Gang Hou1, Dan Han1, Jian Kang1, Qiuyue Wang2. 1. Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China. 2. Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China. Electronic address: qywang2002@hotmail.com.
Abstract
OBJECTIVE: Ursolic acid (UA) is widely distributed in natural plants to against oxidation, virus, inflammation, tumor, and has been widely used in the pharmaceutical and cosmetics. However, its effect on emphysema of chronic obstructive pulmonary disease (COPD) is unknown. Unfolded protein response is involved in pathogenesis of COPD through PERK pathway. Nuclear erythroid-related factor 2 (Nrf2) regulates antioxidant defensive mechanism in COPD. This study was to explore effect and mechanism of UA on cigarette smoke (CS)-induced rat emphysema. MATERIALS AND METHODS: 50 Wistar rats were divided into 5 groups (n = 10 each): rats were exposed to CS for 12 weeks in absence (CS group) or presence of UA at different doses. Control group was treated with UA vehicle only. Histopathology, apoptosis, key protein expression of PERK and Nrf2 pathway were determined in lung tissues. Oxidative stress levels in lung were represented by 8-OHdG, MDA and GSH levels. RESULTS: Emphysema-related pathology, based on inter-alveolar wall distance and alveolar density, was less severe in UA groups than in CS group. Compared with CS group, UA treatment down-regulated PERK pathway protein expression, up-regulated expression of Bcl-2 and down-regulated expression of Bax, Cleaved-Caspase3 and Cleaved-Caspase12. Moreover, UA decreased number of apoptotic cells in rat lungs. UA also up-regulated protein expression of Nrf2/ARE pathway and GSH level, decreased expression of oxidant stress factor 8-OHdG and MDA. These improvements were in accordance with attenuation of severity of emphysema. CONCLUSIONS: UA attenuates CS-induced rat emphysema by down-regulating PERK pathway to alleviate CS-induced apoptosis in lung, and up-regulating Nrf2 pathway to improve cigarette smoke-induced oxidant stress in rat lungs.
OBJECTIVE:Ursolic acid (UA) is widely distributed in natural plants to against oxidation, virus, inflammation, tumor, and has been widely used in the pharmaceutical and cosmetics. However, its effect on emphysema of chronic obstructive pulmonary disease (COPD) is unknown. Unfolded protein response is involved in pathogenesis of COPD through PERK pathway. Nuclear erythroid-related factor 2 (Nrf2) regulates antioxidant defensive mechanism in COPD. This study was to explore effect and mechanism of UA on cigarette smoke (CS)-induced ratemphysema. MATERIALS AND METHODS: 50 Wistar rats were divided into 5 groups (n = 10 each): rats were exposed to CS for 12 weeks in absence (CS group) or presence of UA at different doses. Control group was treated with UA vehicle only. Histopathology, apoptosis, key protein expression of PERK and Nrf2 pathway were determined in lung tissues. Oxidative stress levels in lung were represented by 8-OHdG, MDA and GSH levels. RESULTS:Emphysema-related pathology, based on inter-alveolar wall distance and alveolar density, was less severe in UA groups than in CS group. Compared with CS group, UA treatment down-regulated PERK pathway protein expression, up-regulated expression of Bcl-2 and down-regulated expression of Bax, Cleaved-Caspase3 and Cleaved-Caspase12. Moreover, UA decreased number of apoptotic cells in rat lungs. UA also up-regulated protein expression of Nrf2/ARE pathway and GSH level, decreased expression of oxidant stress factor 8-OHdG and MDA. These improvements were in accordance with attenuation of severity of emphysema. CONCLUSIONS:UA attenuates CS-induced ratemphysema by down-regulating PERK pathway to alleviate CS-induced apoptosis in lung, and up-regulating Nrf2 pathway to improve cigarette smoke-induced oxidant stress in rat lungs.
Authors: Parteek Prasher; Mousmee Sharma; Meenu Mehta; Keshav R Paudel; Saurabh Satija; Dinesh K Chellappan; Harish Dureja; Gaurav Gupta; Murtaza M Tambuwala; Poonam Negi; Peter R Wich; Nicole G Hansbro; Philip M Hansbro; Kamal Dua Journal: Chem Biol Interact Date: 2020-05-04 Impact factor: 5.192