title: Ursolic acid attenuates cigarette smoke-induced emphysema in rats by regulating PERK and Nrf2 pathways.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hou
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Han
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Kang
authors.affiliation: Institute of Respiratory Disease, The First Hospital of China Medical University, Shenyang 110001, China. Electronic address: qywang2002@hotmail.com.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012906:Smoke / Q000009:adverse effects; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D019892:eIF-2 Kinase / Q000235:genetics; D000097245:Ursolic Acid
chemical_list: D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D051267:NF-E2-Related Factor 2; D012906:Smoke; D014315:Triterpenes; D019892:eIF-2 Kinase; D000097245:Ursolic Acid; C495637:Nfe2l2 protein, rat
keywords: Apoptosis; Cigarette smoke; Emphysema; Nrf2; PERK; Unfolded protein response; Ursolic acid