title: Protective effects of liquiritin apioside on cigarette smoke-induced lung epithelial cell injury.
abstract: Cigarette smoking is associated with an increased incidence of chronic obstructive pulmonary disease (COPD). In this study, we hypothesized that liquiritin apioside (LA), a main flavonoid component from Glycyrrhiza uralensis, had antioxidant properties by inducing glutathione (GSH) biosynthesis via the inhibition of cytokines and protected lung epithelial cells against cigarette smoke-mediated oxidative stress. A549 cells were treated with cigarette smoke extract (CSE) and/or LA. ICR mice were exposed to cigarette smoke (CS) for four days with increasing exposure time for up to 6 h per day to elicit epithelial cells injury. One hour before smoke exposure, mice were treated with LA by gavage; 18 h after the last CS exposure all examinations were performed. Treatment with LA concentration-dependently prevented CSE-induced cytotoxicity, increase of TGF-β and TNF-α mRNA expression, depletion of GSH and apoptosis in A549 cells. LA at doses 3, 10 and 30 mg/kg dose-dependently inhibited pulmonary neutrophil and macrophage inflammation. Lung sections of the CS-exposed LA treated mice showed an apparently reduced pulmonary inflammation and a significant inhibitory effect on mucus containing goblet cells in the large airways. Furthermore, the CS-induced pulmonary release of TGF-β, TNF-α and myeloperoxidase activity was reduced, and superoxide dismutase activity was enhanced.These results indicate that protective roles of LA on CS-induced the lung epithelial cell injury are mediated by inhibiting TGF-β and TNF-α expression and increasing anti-oxidative levels of GSH, suggesting that LA might be effective as protective agent against epithelial injury in COPD.
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Yuhangtang Rd-866, Hangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guan
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Li
authors.forename: Ling
authors.initials: L
authors.lastname: Hong
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yan
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tan
authors.forename: Jun-Shan
authors.initials: JS
authors.lastname: He
authors.forename: Xin-Wei
authors.initials: XW
authors.lastname: Dong
authors.forename: Meng-Jing
authors.initials: MJ
authors.lastname: Bao
authors.forename: Qiang-Min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005260:Female; D044950:Flavanones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D029882:Glycyrrhiza uralensis / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D044950:Flavanones; D005419:Flavonoids; D005960:Glucosides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; C512196:liquiritin