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https://doi.org/10.1016/j.taap.2018.10.005
Title: | Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells | Authors: | Tan, WS Daniel Liao, Wupeng Peh, Hong Yong Vila, Merima Dong, Jinrui Shen, Han-Ming Wong, WS Fred |
Keywords: | Science & Technology Life Sciences & Biomedicine Pharmacology & Pharmacy Toxicology p62 LC3B Nrf2 Autophagic flux Apoptosis KEAP1-NRF2 PATHWAY INDUCED APOPTOSIS OXIDATIVE STRESS INHIBITION MECHANISMS MITOPHAGY PROTEINS TARGET DEATH MAPK |
Issue Date: | 1-Dec-2018 | Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | Citation: | Tan, WS Daniel, Liao, Wupeng, Peh, Hong Yong, Vila, Merima, Dong, Jinrui, Shen, Han-Ming, Wong, WS Fred (2018-12-01). Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells. TOXICOLOGY AND APPLIED PHARMACOLOGY 360 : 120-130. ScholarBank@NUS Repository. https://doi.org/10.1016/j.taap.2018.10.005 | Abstract: | Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD). Cigarette smoke heightens oxidative stress and impairs autophagy, advancing COPD progression. Andrographolide is a bioactive diterpenoid lactone isolated from the plant Andrographis paniculata which has been a traditional medicinal herb for respiratory diseases. As airway epithelial cells form the first interface to be exposed to cigarette smoke, this study aimed to explore the modulatory effects of andrographolide on oxidative stress and autophagy in human bronchial epithelial BEAS-2B cells exposed to cigarette smoke extract (CSE). CSE (2%) exposure increased autophagic markers p62 and LC3B-II levels in BEAS-2B cells. Andrographolide alone increased p62 and p-p62 (S349) but not LC3B-II in BEAS-2B cells. However, in the presence of CSE, andrographolide was able to simultaneously increase LC3B-II level and enhance antioxidant defense by decreasing oxidative stress and increasing total antioxidant capacity, through upregulation of nuclear Nrf2 via the p62-Nrf2 positive feedback loop. Using RFP-GFP-LC3B transfected BEAS-2B cells exposed to CSE, andrographolide was found to impair autophagosome fusion with lysosome, which may account for the moderate increase in activated caspase 3/7 and annexin V levels. Our findings revealed for the first time that andrographolide simultaneously upregulated antioxidant defense through the p62-Nrf2 loop and moderately induced apoptosis through impairment of autophagic flux in CSE-exposed bronchial epithelium. Andrographolide facilitated cigarette smoke-induced apoptosis may be a potential toxicological outcome or may protect against chronic inflammation and aberrant DNA repair. Validation of these in-vitro findings in an experimental COPD model by andrographolide is warranted. | Source Title: | TOXICOLOGY AND APPLIED PHARMACOLOGY | URI: | https://scholarbank.nus.edu.sg/handle/10635/239312 | ISSN: | 0041-008X 1096-0333 |
DOI: | 10.1016/j.taap.2018.10.005 |
Appears in Collections: | Staff Publications Elements |
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