Please use this identifier to cite or link to this item: https://doi.org/10.1111/bph.15080
Title: Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease
Authors: Liao, Wupeng 
Lim, Albert YH
Tan, WS Daniel 
Abisheganaden, John
Wong, WS Fred 
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
GLUCOCORTICOID-RECEPTOR
CONCISE GUIDE
SENSITIVITY
INHIBITION
MECHANISMS
PROTECTS
HEALTH
ASTHMA
TARGET
FUTURE
Issue Date: 1-Jun-2020
Publisher: WILEY
Citation: Liao, Wupeng, Lim, Albert YH, Tan, WS Daniel, Abisheganaden, John, Wong, WS Fred (2020-06-01). Restoration of HDAC2 and Nrf2 by andrographolide overcomes corticosteroid resistance in chronic obstructive pulmonary disease. BRITISH JOURNAL OF PHARMACOLOGY 177 (16) : 3662-3673. ScholarBank@NUS Repository. https://doi.org/10.1111/bph.15080
Abstract: Background and Purpose: Corticosteroid resistance poses a major barrier to an effective anti-inflammatory therapy for chronic obstructive pulmonary disease (COPD). The present study aimed to investigate potential corticosteroid re-sensitization actions of andrographolide, a bioactive molecule from the herb Andrographis paniculata, in COPD models, particularly in peripheral blood mononuclear cells (PBMCs) from COPD patients. Experimental Approach: Corticosteroid sensitivity in PBMCs collected from COPD patients, or in human monocytic U937 cells exposed to cigarette smoke extract (CSE), was determined by measuring LPS-induced IL-8 production, in the presence and absence of andrographolide. The mechanisms of corticosteroid re-sensitization action of andrographolide were evaluated in a mouse cigarette smoke (CS)-induced acute lung injury model. Key Results: Impaired inhibition of IL-8 production by dexamethasone was detected in PBMCs from COPD patients and in CSE-exposed U937 cells, together with reduced levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and histone deacetylase-2 (HDAC2). In both PBMCs and CSE-exposed U937 cells, andrographolide restored dexamethasone inhibition of IL-8 production, accompanied by the up-regulation of Nrf2 and HDAC2 levels. In the U937 cells, andrographolide was able to block CSE-induced Akt and reduce the level of c-Jun. Besides, andrographolide also augmented dexamethasone actions on lowering total and neutrophil counts, cytokine levels, and oxidative damage markers in bronchoalveolar lavage fluid from CS-exposed mice. Conclusion and Implications: We report here for the first time a novel corticosteroid re-sensitization property of andrographolide in human PBMCs and provide mechanistic evidence to support clinical evaluation of andrographolide in reversing steroid resistance in COPD.
Source Title: BRITISH JOURNAL OF PHARMACOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/229052
ISSN: 00071188
14765381
DOI: 10.1111/bph.15080
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