Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway
Language: 
English
Abstract: 

BACKGROUND: Phosphoinositide 3-kinase (PI3K)/Akt pathway is linked to the development of asthma. Anti-malarial drug artesunate is a semi-synthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua, and has been shown to inhibit PI3K/Akt activity. We hypothesized that artesunate may attenuate allergic asthma via inhibition of the PI3K/Akt signaling pathway. METHODOLOGY/PRINCIPAL FINDINGS: Female BALB/c mice sensitized and challenged with ovalbumin (OVA) developed airway inflammation. Bronchoalveolar lavage fluid was assessed for total and differential cell counts, and cytokine and chemokine levels. Lung tissues were examined for cell infiltration and mucus hypersecretion, and the expression of inflammatory biomarkers. Airway hyperresponsiveness was monitored by direct airway resistance analysis. Artesunate dose-dependently inhibited OVA-induced increases in total and eosinophil counts, IL-4, IL-5, IL-13 and eotaxin levels in bronchoalveolar lavage fluid. It attenuated OVA-induced lung tissue eosinophilia and airway mucus production, mRNA expression of E-selectin, IL-17, IL-33 and Muc5ac in lung tissues, and airway hyperresponsiveness to methacholine. In normal human bronchial epithelial cells, artesunate blocked epidermal growth factor-induced phosphorylation of Akt and its downstream substrates tuberin, p70S6 kinase and 4E-binding protein 1, and transactivation of NF-?B. Similarly, artesunate blocked the phosphorylation of Akt and its downstream substrates in lung tissues from OVA-challenged mice. Anti-inflammatory effect of artesunate was further confirmed in a house dust mite mouse asthma model. CONCLUSION/SIGNIFICANCE: Artesunate ameliorates experimental allergic airway inflammation probably via negative regulation of PI3K/Akt pathway and the downstream NF-?B activity. These findings provide a novel therapeutic value for artesunate in the treatment of allergic asthma.

Author(s): 
Cheng, Chang
Ho, W. Eugene
Goh, Fera Y.
Guan, Shou Ping
Kong, Li Ren
Lai, Wen-Qi
Leung, Bernard P.
Wong, W. S. Fred
Item Type: 
Journal Article
Publication Title: 
PloS One
Journal Abbreviation: 
PLoS ONE
Publication Date: 
2011
Publication Year: 
2011
Pages: 
e20932
Volume: 
6
Issue: 
6
ISSN: 
1932-6203
DOI: 
10.1371/journal.pone.0020932
Library Catalog: 
PubMed
Extra: 
PMID: 21695271 PMCID: PMC3111464

Turabian/Chicago Citation

Chang Cheng, W. Eugene Ho, Fera Y. Goh, Shou Ping Guan, Li Ren Kong, Wen-Qi Lai, Bernard P. Leung and W. S. Fred Wong. 2011. "Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway." PloS One 6: 6: e20932. 10.1371/journal.pone.0020932.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1371/journal.pone.0020932 | issn = 1932-6203 | volume = 6 | pages = e20932 | last = Cheng | first = Chang | coauthors = Ho, W. Eugene, Goh, Fera Y., Guan, Shou Ping, Kong, Li Ren, Lai, Wen-Qi, Leung, Bernard P., Wong, W. S. Fred | title = Anti-malarial drug artesunate attenuates experimental allergic asthma via inhibition of the phosphoinositide 3-kinase/Akt pathway | journal = PloS One | date = 2011 | pmid = | pmc = }} </ref>