glycyrrhizin exerts antioxidative effects in h5n1 influenza a virus-infected cells and inhibits virus replication and pro-inflammatory gene expression甘草甜素发挥抗氧化作用在h5n1流感病毒感染细胞,抑制病毒复制和促炎症基因的表达.pdfVIP

Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and Pro-Inflammatory Gene Expression Martin Michaelis, Janina Geiler, Patrizia Naczk, Patchima Sithisarn, Anke Leutz, Hans Wilhelm Doerr, Jindrich Cinatl Jr * ¨ ¨ Institut fur Medizinische Virologie, Klinikum der J.W. Goethe-Universitat, Frankfurt am Main, Germany Abstract Glycyrrhizin is known to exert antiviral and anti-inflammatory effects. Here, the effects of an approved parenteral glycyrrhizin preparation (Stronger Neo-Minophafen C) were investigated on highly pathogenic influenza A H5N1 virus replication, H5N1-induced apoptosis, and H5N1-induced pro-inflammatory responses in lung epithelial (A549) cells. Therapeutic glycyrrhizin concentrations substantially inhibited H5N1-induced expression of the pro-inflammatory molecules CXCL10, interleukin 6, CCL2, and CCL5 (effective glycyrrhizin concentrations 25 to 50 mg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 mg/ml or higher). Glycyrrhizin also diminished monocyte migration towards supernatants of H5N1-infected A549 cells. The mechanism by which glycyrrhizin interferes with H5N1 replication and H5N1-induced pro-inflammatory gene expression includes inhibition of H5N1-induced formation of reactive oxygen species and (in turn) reduced activation of NFkB, JNK, and p38, redox- sensitive signalling events known to be relevant for influenza A virus replication. Therefore, glycyrrhizin may complement the arsenal of potential drugs for the treatment of H5N1 disease. Citation: Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A,