ANTI-INFLAMMATORY MECHANISMS OF ANDROGRAPHOLIDE IN CIGARETTE SMOKE-INDUCED LUNG INJURY

Abstract

Chronic obstructive disease (COPD) is characterized by prolonged respiratory symptoms due to alveolar abnormalities. In the first project, with cigarette smoke (CS) being a major risk factor for COPD, a model of COPD exacerbation demonstrated that CS predisposed a heightened inflammation from a non-typeable Haemophilus influenzae (NTHi) infection. Andrographolide reduced the exacerbated lung inflammation through Nrf2. In the second project, CS extract (CSE) decreased autophagic flux and induce cell death in human bronchial epithelial (BEAS-2B) cells. Andrographolide further decreased autophagic flux, sensitizing cells toward CSE-induced cell death. In the third project, CSE enhanced epithelial mesenchymal transition (EMT) in BEAS-2B cells. Andrographolide effect on EMT gene expression was ambiguous, though evidence suggested that andrographolide could be impairing the EMT process. This thesis widens our understanding of andrographolide in COPD exacerbation, autophagy and EMT in order that we might have a holistic understanding in developing it as a novel therapeutic for COPD.