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Antimicrob Agents Chemother. 2015 Oct;59(10):6317-27. doi: 10.1128/AAC.01098-15. Epub 2015 Jul 27.

The Flavonoid Isoliquiritigenin Reduces Lung Inflammation and Mouse Morbidity during Influenza Virus Infection.

Author information

1
Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada.
2
Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Institut de Pharmacologie de Sherbrooke, Sherbooke, Québec, Canada.
3
Department of Medicine, Pulmonary Division, Faculty of Medicine and Health Sciences, Université de Sherbrooke, and Centre de recherche du CHUS, Sherbrooke, Québec, Canada Martin.Richter@USherbrooke.ca.

Abstract

The host response to influenza virus infection is characterized by an acute lung inflammatory response in which intense inflammatory cell recruitment, hypercytokinemia, and a high level of oxidative stress are present. The sum of these events contributes to the virus-induced lung damage that leads to high a level of morbidity and mortality in susceptible infected patients. In this context, we identified compounds that can simultaneously reduce the excessive inflammatory response and the viral replication as a strategy to treat influenza virus infection. We investigated the anti-inflammatory and antiviral potential activities of isoliquiritigenin (ILG). Interestingly, we demonstrated that ILG is a potent inhibitor of influenza virus replication in human bronchial epithelial cells (50% effective concentration [EC50] = 24.7 μM). In addition, our results showed that this molecule inhibits the expression of inflammatory cytokines induced after the infection of cells with influenza virus. We demonstrated that the anti-inflammatory activity of ILG in the context of influenza virus infection is dependent on the activation of the peroxisome proliferator-activated receptor gamma pathway. Interestingly, ILG phosphate (ILG-p)-treated mice displayed decreased lung inflammation as depicted by reduced cytokine gene expression and inflammatory cell recruitment. We also demonstrated that influenza virus-specific CD8(+) effector T cell recruitment was reduced up to 60% in the lungs of mice treated with ILG-p (10 mg/kg) compared to that in saline-treated mice. Finally, we showed that administration of ILG-p reduced lung viral titers and morbidity of mice infected with the PR8/H1N1 virus.

PMID:
26248373
PMCID:
PMC4576023
DOI:
10.1128/AAC.01098-15
[Indexed for MEDLINE]
Free PMC Article

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