title: Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity.
abstract: OBJECTIVE
  Cigarette smoke is a major cause for chronic obstructive pulmonary disease (COPD). Andrographolide is an active biomolecule isolated from the plant Andrographis paniculata. Andrographolide has been shown to activate nuclear factor erythroid-2-related factor 2 (Nrf2), a redox-sensitive antioxidant transcription factor. As Nrf2 activity is reduced in COPD, we hypothesize that andrographolide may have therapeutic value for COPD.
  
  
  METHODS
  Andrographolide was given i.p. to BALB/c mice daily 2h before 4% cigarette smoke exposure for 1h over five consecutive days. Bronchoalveolar lavage fluid and lungs were collected for analyses of cytokines, oxidative damage markers and antioxidant activities. BEAS-2B bronchial epithelial cells were exposed to cigarette smoke extract (CSE) and used to study the antioxidant mechanism of action of andrographolide.
  
  
  RESULTS
  Andrographolide suppressed cigarette smoke-induced increases in lavage fluid cell counts; levels of IL-1β, MCP-1, IP-10 and KC; and levels of oxidative biomarkers 8-isoprostane, 8-OHdG and 3-nitrotyrosine in a dose-dependent manner. Andrographolide promoted inductions of glutathione peroxidase (GPx) and glutathione reductase (GR) activities in lungs from cigarette smoke-exposed mice. In BEAS-2B cells, andrographolide markedly increased nuclear Nrf2 accumulation, promoted binding to antioxidant response element (ARE) and total cellular glutathione level in response to CSE. Andrographolide up-regulated ARE-regulated gene targets including glutamate-cysteine ligase catalytic (GCLC) subunit, GCL modifier (GCLM) subunit, GPx, GR and heme oxygenase-1 in BEAS-2B cells in response to CSE.
  
  
  CONCLUSIONS
  Andrographolide possesses antioxidative properties against cigarette smoke-induced lung injury probably via augmentation of Nrf2 activity and may have therapeutic potential for treating COPD.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, Singapore.
authors.forename: S P
authors.initials: SP
authors.lastname: Guan
authors.forename: W
authors.initials: W
authors.lastname: Tee
authors.forename: D S W
authors.initials: DS
authors.lastname: Ng
authors.forename: T K
authors.initials: TK
authors.lastname: Chan
authors.forename: H Y
authors.initials: HY
authors.lastname: Peh
authors.forename: W E
authors.initials: WE
authors.lastname: Ho
authors.forename: C
authors.initials: C
authors.lastname: Cheng
authors.forename: J C
authors.initials: JC
authors.lastname: Mak
authors.forename: W S F
authors.initials: WS
authors.lastname: Wong
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000209:etiology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D016207:Cytokines; D004224:Diterpenes; D051267:NF-E2-Related Factor 2; C030419:andrographolide; D051547:Heme Oxygenase-1; D005978:Glutathione