Effects of flavonoid-induced oxidative stress on anti-H5N1 influenza a virus activity exerted by baicalein and biochanin A

BMC Research Notes

Jindrich Cinatl Jr¹  Patchima Sithisarn²  Martin Michaelis³ 

[1] Institute for Medical Virology, Clinics of the Goethe-University, Paul Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany;Current address: Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand;Current address: Centre for Molecular Processing and School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK

关键词: N-acetyl-L-cysteine;    Reactive oxygen species;    Antiviral;    Baicalein;    Biochanin A;    H5N1;   

Others  :  1132406
DOI  :  10.1186/1756-0500-7-384

 received in 2014-04-24, accepted in 2014-06-13,  发布年份 2014

【 摘 要 】

Background

Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.

Findings

Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.

Conclusions

These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.

【 授权许可】

   
2014 Michaelis et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Cheung CL, Rayner JM, Smith GJ, Wang P, Naipospos TS, Zhang J, Yuen KY, Webster RG, Peiris JS, Guan Y, Chen H: Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006, 193:1626-1629.
• [2]de Jong MD: H5N1 transmission and disease: observations from the frontlines. Pediatr Infect Dis J 2008, 27:S54-S56.
• [3]Hien ND, Ha NH, Van NT, Ha NT, Lien TT, Thai NQ, Trang VD, Shimbo T, Takahashi Y, Kato Y, Kawana A, Akita S, Kudo K: Human infection with highly pathogenic avian influenza virus (H5N1) in northern Vietnam, 2004–2005. Emerg Infect Dis 2009, 15:19-23.
• [4]McKimm-Breschkin JL, Selleck PW, Usman TB, Johnson MA: Reduced sensitivity of influenza A (H5N1) to oseltamivir. Emerg Infect Dis 2007, 13:1354-1357.
• [5]Deyde VM, Xu X, Bright RA, Shaw M, Smith CB, Zhang Y, Shu Y, Gubareva LV, Cox NJ, Klimov AI: Surveillance of resistance to adamantanes among influenza A(H3N2) and A(H1N1) viruses isolated worldwide. J Infect Dis 2007, 196:249-257.
• [6]Hampson AW: Vaccines for pandemic influenza. The history of our current vaccines, their limitations and the requirements to deal with a pandemic threat. Ann Acad Med Singapore 2008, 37:510-517.
• [7]Kieny MP, Fukuda K: The pandemic influenza vaccine challenge. Vaccine 2008, 26(Suppl 4):D3-D4.
• [8]Sugrue RJ, Tan BH, Yeo DS, Sutejo R: Antiviral drugs for the control of pandemic influenza virus. Ann Acad Med Singapore 2008, 37:518-524.
• [9]van der Vries E, van den Berg B, Schutten M: Fatal oseltamivir-resistant influenza virus infection. N Engl J Med 2008, 359:1074-1076.
• [10]Michaelis M, Doerr HW, Cinatl J Jr: Of chickens and men: avian influenza in humans. Curr Mol Med 2009, 9:131-151.
• [11]Moscona A: Global transmission of oseltamivir-resistant influenza. N Engl J Med 2009, 360:953-956.
• [12]Bavagnoli L, Maga G: The 2009 influenza pandemic: promising lessons for antiviral therapy for future outbreaks. Curr Med Chem 2011, 18:5466-5475.
• [13]Salter A, Ni LB, Crowley B: Emergence and phylogenetic analysis of amantadine-resistant influenza a subtype H3N2 viruses in Dublin, Ireland, over Six Seasons from 2003/2004 to 2008/2009. Intervirology 2011, 54:305-315.
• [14]Harborne JB, Williams CA: Advances in flavonoid research since 1992. Phytochemistry 2000, 55:481-504.
• [15]Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA: Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001, 74:418-425.
• [16]Kim Y, Narayanan S, Chang KO: Inhibition of influenza virus replication by plant-derived isoquercetin. Antiviral Res 2010, 88:227-235.
• [17]Xu G, Dou J, Zhang L, Guo Q, Zhou C: Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum. Biol Pharm Bull 2010, 33:238-243.
• [18]Chen L, Dou J, Su Z, Zhou H, Wang H, Zhou W, Guo Q, Zhou C: Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice. Antiviral Res 2011, 91:314-320.
• [19]Grienke U, Schmidtke M, von Grafenstein S, Kirchmair J, Liedl KR, Rollinger JM: Influenza neuraminidase: a druggable target for natural products. Nat Prod Rep 2012, 29:11-36.
• [20]Wang X, Jia W, Zhao A, Wang X: Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res 2006, 20:335-341.
• [21]Liu AL, Wang HD, Lee SM, Wang YT, Du GH: Structure-activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities. Bioorg Med Chem 2008, 16:7141-7147.
• [22]Song JM, Park KD, Lee KH, Byun YH, Park JH, Kim SH, Kim JH, Seong BL: Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives. Antiviral Res 2007, 76:178-185.
• [23]Biswas SK, McClure D, Jimenez LA, Megson IL, Rahman I: Curcumin induces glutathione biosynthesis and inhibits NF-kappaB activation and interleukin-8 release in alveolar epithelial cells: mechanism of free radical scavenging activity. Antioxid Redox Signal 2005, 7:32-41.
• [24]Hecht SS, Huang C, Stoner GD, Li J, Kenney PM, Sturla SJ, Carmella SG: Identification of cyanidin glycosides as constituents of freeze-dried black raspberries which inhibit anti-benzo[a]pyrene-7,8-diol-9,10-epoxide induced NFkappaB and AP-1 activity. Carcinogenesis 2006, 27:1617-1626.
• [25]Sen P, Chakraborty PK, Raha S: Tea polyphenol epigallocatechin 3-gallate impedes the anti-apoptotic effects of low-grade repetitive stress through inhibition of Akt and NFkappaB survival pathways. FEBS Lett 2006, 580:278-284.
• [26]Cavet ME, Harrington KL, Vollmer TR, Ward KW, Zhang JZ: Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells. Mol Vis 2011, 17:533-542.
• [27]Kole L, Giri B, Manna SK, Pal B, Ghosh S: Biochanin-A, an isoflavon, showed anti-proliferative and anti-inflammatory activities through the inhibition of iNOS expression, p38-MAPK and ATF-2 phosphorylation and blocking NFkappaB nuclear translocation. Eur J Pharmacol 2011, 653:8-15.
• [28]Sithisarn P, Michaelis M, Schubert-Zsilavecz M, Cinatl J Jr: Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Res 2013, 97:41-48.
• [29]Shin YK, Liu Q, Tikoo SK, Babiuk LA, Zhou Y: Effect of the phosphatidylinositol 3-kinase/Akt pathway on influenza A virus propagation. J Gen Virol 2007, 88:942-950.
• [30]Geiler J, Michaelis M, Sithisarn P, Cinatl J Jr: Comparison of pro-inflammatory cytokine expression and cellular signal transduction in human macrophages infected with different influenza A viruses. Med Microbiol Immunol 2011, 200:53-60.
• [31]Ludwig S: Disruption of virus-host cell interactions and cell signaling pathways as an anti-viral approach against influenza virus infections. Biol Chem 2011, 392:837-847.
• [32]Pinto R, Herold S, Cakarova L, Hoegner K, Lohmeyer J, Planz O, Pleschka S: Inhibition of influenza virus-induced NF-kappaB and Raf/MEK/ERK activation can reduce both virus titers and cytokine expression simultaneously in vitro and in vivo. Antiviral Res 2011, 92:45-56.
• [33]Khan HY, Zubair H, Ullah MF, Ahmad A, Hadi SM: A prooxidant mechanism for the anticancer and chemopreventive properties of plant polyphenols. Curr Drug Targets 2012, 13:1738-1749.
• [34]Vlahos R, Stambas J, Selemidis S: Suppressing production of reactive oxygen species (ROS) for influenza A virus therapy. Trends Pharmacol Sci 2012, 33:3-8.
• [35]Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J Jr: N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus. Biochem Pharmacol 2010, 79:413-420.
• [36]Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, Doerr HW, Cinatl J Jr: Glycyrrhizin exerts antioxidative effects in H5N1 influenza A virus-infected cells and inhibits virus replication and pro-inflammatory gene expression. PLoS One 2011, 6:e19705.