Oxidative stress is a critical pathophysiological factor for the development of allergic airway inflammation, resulting in oxidative damage to pulmonary lipids, proteins, and DNA. Our research has previously demonstrated potent anti-inflammatory effects of the anti-malarial drug artesunate in experimental allergic asthma. The present study investigated potential anti-oxidative effects of artesunate in a murine model of allergic asthma in comparison with dexamethasone, a potent corticosteroid. BALB/C mice, sensitized and challenged with ovalbumin, developed airway inflammation and oxidative lung damage. Artesunate markedly suppressed increases in total cell, eosinophil and neutrophil counts. Oxidative damage markers, 8-isoprostane, 8-hydroxy-2-deoxy-guanosine and 3-nitrotyrosine levels were potently repressed by artesunate. Pro-oxidants' expressions, iNOS and NADPH oxidase (NOX 1, 2, 3 and 4) were significantly abated by artesunate. Gene expressions of NOX regulatory subunits, p22phox and p67phox, were also reduced by artesunate. Expressions, protein levels and activities of antioxidants superoxide dismutase and catalase were substantially reversed with artesunate in ovalbumin-challenged mice. Both in vitro and in vivo findings consistently suggest that artesunate may promote nuclear Nrf2 levels. Our findings implicate a potential therapeutic value for artesunate in the treatment of asthma by ameliorating oxidative damage in allergic airways, suppressing pro-oxidants' and restoring antioxidants' activities and expressions via activation of Nrf2. A biotin-linked derivative of artesunate  has been prepared  for fishing target proteins from Beas2B lung epithelial cells as an in vitro model for asthma.

Antimalarial drug artesunate ameliorates oxidative lung damage in experimental allergic asthma

248th National Meeting (2014)

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