title: Wedelolactone protects human bronchial epithelial cell injury against cigarette smoke extract-induced oxidant stress and inflammation responses through Nrf2 pathway.
abstract: Cigarette smoke is the leading cause of the development of various lung diseases including lung cancer through triggering oxidant stress and inflammatory responses which contributed to the lesions of normal human bronchial epithelial (NHBE) cell. Wedelolactone (WEL), a natural compound from Eclipta prostrata L., has been found to possess the inhibitive effects on the proliferation and growth of cancers. In the present study, we investigated the effects of WEL on NHBE cell injury induced by cigarette smoke extract (CSE) in vitro. It showed that the pretreatment WEL (2.5-20μM) resulted in a significant protective effect on 10% CSE-induced cell death in NHBE cells. The pretreatment with WEL dose-dependently and significantly reversed the activities of SOD, CAT, GSH and the level of MDA to normal level. We also found that the protein expression levels of COX-2 and ICAM-1 which are related to inflammatory response were remarkably reduced by WEL compared with 10% CSE treatment. Additionally, WEL also reduced the expressions of antioxidases including NAD(P)H dehydrogenase:Quinone 1 (NQO1) and heme oxygenase-1 (HO-1). Moreover, Nrf2 inhibitor all-trans-retinoic acid (ATRA) decreased remarkably their expressions. These results suggest that WEL protects NHBE cell against CSE-induced injury through modulating Nrf2 pathway. Our study indicates that WEL may be a new potential protective agent against CSE-induced lung injury.
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China; School of Pharmaceutial Engineering and Life Science, Changzhou University, Changzhou, Jiangsu 213164, PR China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Ding
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230012, PR China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Hou
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 230012, PR China.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Tan
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 230012, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 230012, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Oncology, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Oncology, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 230012, PR China; Jumpcan Pharmaceutical Co., Ltd., Taixing 225400, PR China. Electronic address: 13961098521@163.com.
authors.forename: Zibo
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China. Electronic address: wenmoxiushi@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, PR China. Electronic address: jxiaobin2005@hotmail.com.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Jia
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology*; D002460:Cell Line; D045424:Complex Mixtures / Q000737:chemistry / Q000633:toxicity*; D003374:Coumarins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D015394:Molecular Structure; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity; D020545:Respiratory Mucosa / Q000166:cytology; D012906:Smoke / Q000032:analysis*; D013312:Stress, Physiological; D062789:Tobacco Products
chemical_list: D000975:Antioxidants; D045424:Complex Mixtures; D003374:Coumarins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D016877:Oxidants; D012906:Smoke; C051122:wedelolactone; D018799:Intercellular Adhesion Molecule-1; D051546:Cyclooxygenase 2
keywords: Antioxidant; Chemoprevention; Cigarette smoke; Inflammatory; Lung cancer; Wedelolactone