Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-infected Cells and Inhibits Virus Replication and Pro-inflammatory Gene Expression

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2011 May 26

PMID 21611183

Citations 78

Authors

Martin Michaelis

Janina Geiler

Patrizia Naczk

Patchima Sithisarn

Anke Leutz

Hans Wilhelm Doerr

Jindrich Cinatl Jr

Affiliations

Soon will be listed here.

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 µg/ml) but interfered with H5N1 replication and H5N1-induced apoptosis to a lesser extent (effective glycyrrhizin concentrations 100 µg/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 NFκB, 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.

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References

Hien N, Ha N, Van N, Ha N, Lien T, Thai N . Human infection with highly pathogenic avian influenza virus (H5N1) in northern Vietnam, 2004-2005. Emerg Infect Dis. 2009; 15(1):19-23. PMC: 2660684. DOI: 10.3201/eid1501.080073. View

Wurzer W, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S . Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J. 2003; 22(11):2717-28. PMC: 158404. DOI: 10.1093/emboj/cdg279. View

Ludwig S . Targeting cell signalling pathways to fight the flu: towards a paradigm change in anti-influenza therapy. J Antimicrob Chemother. 2009; 64(1):1-4. DOI: 10.1093/jac/dkp161. View

Mazur I, Wurzer W, Ehrhardt C, Pleschka S, Puthavathana P, Silberzahn T . Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity. Cell Microbiol. 2007; 9(7):1683-94. DOI: 10.1111/j.1462-5822.2007.00902.x. View

Wolkerstorfer A, Kurz H, Bachhofner N, Szolar O . Glycyrrhizin inhibits influenza A virus uptake into the cell. Antiviral Res. 2009; 83(2):171-8. PMC: 7126985. DOI: 10.1016/j.antiviral.2009.04.012. View

Saito R, Li D, Suzuki Y, Sato I, Masaki H, Nishimura H . High prevalence of amantadine-resistance influenza a (H3N2) in six prefectures, Japan, in the 2005-2006 season. J Med Virol. 2007; 79(10):1569-76. DOI: 10.1002/jmv.20946. View

Cinatl Jr J, Michaelis M, Doerr H . The threat of avian influenza A (H5N1). Part IV: Development of vaccines. Med Microbiol Immunol. 2007; 196(4):213-25. DOI: 10.1007/s00430-007-0052-3. View

Salomon R, Hoffmann E, Webster R . Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection. Proc Natl Acad Sci U S A. 2007; 104(30):12479-81. PMC: 1924467. DOI: 10.1073/pnas.0705289104. View

Nassiri Asl M, Hosseinzadeh H . Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res. 2008; 22(6):709-24. PMC: 7167813. DOI: 10.1002/ptr.2362. View

10.

Michaelis M, Doerr H, Cinatl Jr J . Of chickens and men: avian influenza in humans. Curr Mol Med. 2009; 9(2):131-51. DOI: 10.2174/156652409787581565. View

11.

Cheung C, Rayner J, Smith G, Wang P, Naipospos T, Zhang J . Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis. 2006; 193(12):1626-9. DOI: 10.1086/504723. View

12.

Michaelis M, Geiler J, Klassert D, Doerr H, Cinatl Jr J . Infection of human retinal pigment epithelial cells with influenza A viruses. Invest Ophthalmol Vis Sci. 2009; 50(11):5419-25. DOI: 10.1167/iovs.09-3752. View

13.

Suzuki Y, Taira K, Saito R, Nidaira M, Okano S, Zaraket H . Epidemiologic study of influenza infection in Okinawa, Japan, from 2001 to 2007: changing patterns of seasonality and prevalence of amantadine-resistant influenza A virus. J Clin Microbiol. 2009; 47(3):623-9. PMC: 2650946. DOI: 10.1128/JCM.01760-08. View

14.

Hui K, Lee S, Cheung C, Ng I, Poon L, Guan Y . Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK. J Immunol. 2009; 182(2):1088-98. DOI: 10.4049/jimmunol.182.2.1088. View

15.

Ludwig S, Planz O . Influenza viruses and the NF-kappaB signaling pathway - towards a novel concept of antiviral therapy. Biol Chem. 2008; 389(10):1307-12. DOI: 10.1515/BC.2008.148. View

16.

McCubrey J, Lahair M, Franklin R . Reactive oxygen species-induced activation of the MAP kinase signaling pathways. Antioxid Redox Signal. 2006; 8(9-10):1775-89. DOI: 10.1089/ars.2006.8.1775. View

17.

Aldridge Jr J, Moseley C, Boltz D, Negovetich N, Reynolds C, Franks J . TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A. 2009; 106(13):5306-11. PMC: 2664048. DOI: 10.1073/pnas.0900655106. View

18.

Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, Armanini D . Antiviral effects of Glycyrrhiza species. Phytother Res. 2007; 22(2):141-8. PMC: 7167979. DOI: 10.1002/ptr.2295. View

19.

Geiss G, An M, Bumgarner R, Hammersmark E, Cunningham D, Katze M . Global impact of influenza virus on cellular pathways is mediated by both replication-dependent and -independent events. J Virol. 2001; 75(9):4321-31. PMC: 114177. DOI: 10.1128/JVI.75.9.4321-4331.2001. View

20.

Kieny M, Fukuda K . The pandemic influenza vaccine challenge. Vaccine. 2009; 26 Suppl 4:D3-4. DOI: 10.1016/j.vaccine.2008.07.046. View