Document Detail


Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity.
MedLine Citation:
PMID:  23146110     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: 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.
EXPERIMENTAL APPROACH: 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.
KEY 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:
S P Guan; W Tee; D S W Ng; T K Chan; H Y Peh; W E Ho; C Cheng; J C Mak; W S F Wong
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  168     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-15     Completed Date:  2013-11-25     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1707-18     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*
Bronchoalveolar Lavage Fluid / cytology
Cells, Cultured
Cytokines / metabolism
Diterpenes / pharmacology*
Female
Glutathione / genetics,  metabolism
Heme Oxygenase-1 / genetics,  metabolism
Inflammation / etiology,  metabolism,  pathology
Lung / immunology,  metabolism,  pathology
Lung Injury / etiology,  metabolism,  prevention & control*
Mice
Mice, Inbred BALB C
NF-E2-Related Factor 2 / genetics,  metabolism*
Oxidation-Reduction
Pulmonary Disease, Chronic Obstructive / drug therapy,  etiology
Respiratory Mucosa / drug effects,  metabolism
Smoking / adverse effects*
Up-Regulation / drug effects
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Cytokines; 0/Diterpenes; 0/NF-E2-Related Factor 2; 410105JHGR/andrographolide; EC 1.14.99.3/Heme Oxygenase-1; GAN16C9B8O/Glutathione
Comments/Corrections

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