Premium
Andrographolide protects against cigarette smoke‐induced oxidative lung injury via augmentation of Nrf2 activity
Author(s) -
Guan SP,
Tee W,
Ng DSW,
Chan TK,
Peh HY,
Ho WE,
Cheng C,
Mak JC,
Wong WSF
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12054
Subject(s) - andrographolide , gclm , gclc , glutathione , oxidative stress , andrographis paniculata , pharmacology , antioxidant , chemistry , glutathione peroxidase , glutathione reductase , heme oxygenase , biochemistry , medicine , superoxide dismutase , heme , pathology , enzyme , alternative medicine
Background and Purpose Cigarette smoke is a major cause for chronic obstructive pulmonary disease ( COPD ). Andrographolide is an active biomolecule isolated from the plant A ndrographis 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 2 h before 4% cigarette smoke exposure for 1 h 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 .