Tan Wan Shun, Daniel
Email Address
phctwsd@nus.edu.sg
Organizational Units
YONG LOO LIN SCH OF MEDICINE
faculty
PHARMACOLOGY
dept
5 results
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Now showing 1 - 5 of 5
Publication A Unique CD27-IgD(-) B Cell Population in the Sputum of Severe Eosinophilic Asthma Associated with Airway Autoimmunity(AMER THORACIC SOC, 2022-10-01) Tan, Nadia Suray; Mukherjee, Manali; Lim, Sheau Yng; Rouers, Angeline; Hwang, You Yi; Thiam, Chung Hwee; Tan, WS Daniel; Liao, Wupeng; Wong, WS Fred; Liew, Mei Fong; Nair, Parameswaran; Larbi, Anis; Wang, De Yun; Fink, Katja; Angeli, Veronique; Lim, Hui Fang; Prof Wai-Shiu Fred Wong; PHARMACOLOGY; MEDICINE; MICROBIOLOGY AND IMMUNOLOGY; PHARMACYPublication Andrographolide simultaneously augments Nrf2 antioxidant defense and facilitates autophagic flux blockade in cigarette smoke-exposed human bronchial epithelial cells(ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018-12-01) Tan, WS Daniel; Liao, Wupeng; Peh, Hong Yong; Vila, Merima; Dong, Jinrui; Shen, Han-Ming; Wong, WS Fred; Prof Wai-Shiu Fred Wong; PHARMACOLOGY; DEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)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.Publication Dysregulated autophagy in COPD: A pathogenic process to be deciphered(ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2019-06-01) Tan, WS Daniel; Shen, Han-Ming; Wong, WS Fred; Prof Wai-Shiu Fred Wong; PHARMACOLOGY; PHYSIOLOGYAutophagy is an evolutionary conserved process that is responsible for maintaining cellular homeostasis through lysosome-dependent degradation of damaged proteins, lipid and organelles. When autophagy is dysregulated by factors such as cigarette smoking, environmental insults and ageing, it can lead to formation of aggresome-bodies and enhanced production of reactive oxygen species (ROS), of which contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). This review will aim to decipher the pathogenic process of autophagy that is dysregulated by the various risk factors of COPD, leading to either cell death or senescence and COPD progression. It will also cover potential therapeutics that can be used to augment autophagy for the treatment of COPD. This will help shed light on COPD pathophysiology in the context of autophagy so that novel therapeutics can be developed to provide target-specific treatment.Publication From irreversible to reversible covalent inhibitors: Harnessing the andrographolide scaffold for anti-inflammatory action (vol 204, 112481, 2020)(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2021-01-01) Tran, Quy TN; Tan, WS Daniel; Wong, WS Fred; Chai, Christina LL; Prof Wai-Shiu Fred Wong; PHARMACOLOGY; PHARMACYThe authors regret an error in Figure 7 in the published article due to conversion problems from Mac to PC during the production of proofs. The μM appeared as αM. The corrected version is provided below. This correction does not change the conclusions of the article. [Figure presented] The authors would like to apologise for any inconvenience caused.Publication Polypharmacology of andrographolide: beyond one molecule one target(ROYAL SOC CHEMISTRY, 2021-04-01) Tran, Quy TN; Tan, WS Daniel; Wong, WS Fred; Chai, Christina LL; Prof Wai-Shiu Fred Wong; PHARMACOLOGY; PHARMACYCovering: 1951 to 2020 Andrographolide is one of the most widely studied plant secondary metabolites, known to display diverse pharmacological actions. Current literature has documented a sizeable list of pharmacological targets for andrographolide, suggesting its multi-targeting nature. Many of these targets are central to the pathophysiology of highly prevalent diseases such as cardiovascular diseases, neurodegenerative disorders, autoimmunity, and even cancer. Despite its well-documented therapeutic efficacy in various disease models, for years, the discrepancies between in vivo bioavailability and bioactivity of andrographolide and the debate surrounding its multi-targeting properties (polypharmacology or promiscuity?) have hindered the development of this versatile molecule into a potential therapeutic agent. Is andrographolide a valuable lead for therapeutic development or a potential invalid metabolic panacea (IMP)? This perspective article aims to discuss this by considering various contributing factors to the polypharmacology of andrographolide.