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Article: Andrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity

TitleAndrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activity
Authors
Issue Date2013
Citation
Br. J. Pharmacol., 2013, v. 168 n. 7, p. 1707-1718 How to Cite?
AbstractBACKGROUND 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-1beta, 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.
Persistent Identifierhttp://hdl.handle.net/10722/188236
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorGuan, S-
dc.contributor.authorTee, W-
dc.contributor.authorNg, D-
dc.contributor.authorChan, T-
dc.contributor.authorPeh, H-
dc.contributor.authorHo, W-
dc.contributor.authorCheng, C-
dc.contributor.authorMak, JCW-
dc.contributor.authorWong, WS-
dc.date.accessioned2013-08-23T04:47:37Z-
dc.date.available2013-08-23T04:47:37Z-
dc.date.issued2013-
dc.identifier.citationBr. J. Pharmacol., 2013, v. 168 n. 7, p. 1707-1718-
dc.identifier.urihttp://hdl.handle.net/10722/188236-
dc.description.abstractBACKGROUND 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-1beta, 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.-
dc.languageeng-
dc.relation.ispartofBr. J. Pharmacol.-
dc.titleAndrographolide protects against cigarette smoke-induced oxidative lung injury via augmentation of Nrf2 activityen_US
dc.typeArticleen_US
dc.identifier.emailMak, JCW: judymak@hkucc.hku.hk-
dc.identifier.doi10.1111/bph.12054-
dc.identifier.pmid23146110-
dc.identifier.pmcidPMC3605877-
dc.identifier.hkuros220857-
dc.identifier.volume168-
dc.identifier.issue7-
dc.identifier.spage1707-
dc.identifier.epage1718-
dc.identifier.isiWOS:000316262500014-

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