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Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase

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Abstract

Scutellaria baicalensis Georgi, a Chinese herbal decoction, has been used for the treatment of the common cold, fever and influenza virus infections. In previous studies, we found that oral administration of baicalein resulted in the inhibition of influenza A virus replication in vivo, which was linked to baicalin in serum. However, the effective dose and underlying mechanisms of the efficacy of baicalin against influenza A virus have not been fully elucidated. In this study, the antiviral effects of baicalin in influenza-virus-infected MDCK cells and mice were examined. The neuraminidase inhibition assay was performed to investigate the mechanism of action of baicalin. In vitro results showed that baicalin exhibited a half-maximal effective concentration (EC50) of 43.3 μg/ml against the influenza A/FM1/1/47 (H1N1) virus and 104.9 μg/ml against the influenza A/Beijing/32/92 (H3N2) virus. When added to MDCK cell cultures after inoculation with influenza virus, baicalin demonstrated obvious antiviral activity that increased in a dose-dependent manner, indicating that baicalin affected virus budding. Baicalin had clear inhibitory effects against neuraminidases, with half-maximal inhibitory concentration (IC50) of 52.3 μg/ml against the influenza A/FM1/1/47 (H1N1) virus and 85.8 μg/ml against the influenza A/Beijing/32/92 (H3N2) virus. In vivo studies showed that an intravenous injection of baicalin effectively reduced the death rate, prolonged the mean day to death (MDD) and improved the lung parameters of mice infected with influenza A virus. These results demonstrate that baicalin acts as a neuraminidase inhibitor, with clear inhibitory activities that are effective against different strains of influenza A virus in both cell culture and a mouse model, and that baicalin has potential utility in the management of influenza virus infections.

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References

  1. García-García J, Ramos C (2006) Influenza, an existing public health problem. Salud Publica Mex 48:244–267

    Article  PubMed  Google Scholar 

  2. Fraser C, Donnelly CA, Cauchemez S, Hanage WP et al (2009) Pandemic potential of a strain of influenza A (H1N1): early findings. Science 324:1557–1561

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Neumann G, Chen H, Gao GF, Shu Y, Kawaoka Y (2010) H5N1 influenza viruses: outbreaks and biological properties. Cell Res 20:51–61

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Droebner K, Pleschka S, Ludwig S, Planz O (2011) Antiviral activity of the MEK-inhibitor U0126 against pandemic H1N1v and highly pathogenic avian influenza virus in vitro and in vivo. Antiviral Res 92:195–203

    Article  CAS  PubMed  Google Scholar 

  5. Muratore G, Goracci L, Mercorelli B, Foeglein Á, Digard P, Cruciani G, Palù G, Loregian A (2012) Small molecule inhibitors of influenza A and B viruses that act by disrupting subunit interactions of the viral polymerase. Proc Natl Acad Sci 109:6247–6252

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. De Clercq E (2006) Antiviral agents active against influenza A viruses. Nat Rev Drug Discov 5:1015–1025

    Article  PubMed  Google Scholar 

  7. Deyde VM, Nguyen T, Bright RA et al (2009) Detection of molecular markers of antiviral resistance in influenza A (H5N1) viruses using a pyrosequencing method. Antimicrob Agents Chemother 53:1039–1047

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Baranovich T, Saito R, Suzuki Y et al (2010) Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008–2009 season. J Clin Virol 47:23–28

    Article  CAS  PubMed  Google Scholar 

  9. Hsieh CF, Lo CW, Liu CH, Lin S, Yen HR, Lin TY, Horng JT (2012) Mechanism by which ma-xing-shi-gan-tang inhibits the entry of influenza virus. J Ethnopharmacol 143:57–67

    Article  PubMed  Google Scholar 

  10. Das K, Aramini JM, Ma LC, Krug RM, Arnold E (2010) Structures of influenza A proteins and insights into antiviral drug targets. Nat Struct Mol Biol 17:530–538

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Spackman E (2008) A brief introduction to the avian influenza virus. Methods Mol Biol 436:1–6

    CAS  PubMed  Google Scholar 

  12. Su B, Wurtzer S, Rameix-Welti MA et al (2009) Enhancement of the influenza A hemagglutinin (HA)-mediated cell-cell fusion and virus entry by the viral neuraminidase (NA). PLoS One 4:e8495

    Article  PubMed Central  PubMed  Google Scholar 

  13. Chen L, Dou J, Su Z, Zhou H, Wang H, Zhou W, Guo Q, Zhou C (2011) Synergistic activity of baicalein with ribavirin against influenza A (H1N1) virus infections in cell culture and in mice. Antiviral Res 91:314–320

    Article  CAS  PubMed  Google Scholar 

  14. Grienke U, Schmidtke M, von Grafenstein S, Kirchmair J, Liedl KR, Rollinger JM (2012) Influenza neuraminidase: a druggable target for natural products. Nat Prod Rep 29:11–36

    Article  CAS  PubMed  Google Scholar 

  15. Harborne JB, Williams CA (2000) Advances in flavonoid research since 1992. Phytochemistry 55:481–504

    Article  CAS  PubMed  Google Scholar 

  16. Nijveldt RJ, van Nood E, van Hoorn DE, Boelens PG, van Norren K, van Leeuwen PA (2001) Flavonoids: a review of probable mechanisms of action and potential applications. Am J Clin Nutr 74:418–425

    CAS  PubMed  Google Scholar 

  17. Wang X, Jia W, Zhao A, Wang X (2006) Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res 20:335–341

    Article  CAS  PubMed  Google Scholar 

  18. Liu AL, Wang HD, Lee SM, Wang YT, Du GH (2008) Structure-activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities. Bioorg Med Chem 16:7141–7147

    Article  CAS  PubMed  Google Scholar 

  19. Song JM, Park KD, Lee KH et al (2007) Biological evaluation of anti-influenza viral activity of semi-synthetic catechin derivatives. Antiviral Res 76:178–185

    Article  CAS  PubMed  Google Scholar 

  20. Sithisarn P, Michaelis M, Schubert-Zsilavecz M, Cinatl J Jr (2013) Differential antiviral and anti-inflammatory mechanisms of the flavonoids biochanin A and baicalein in H5N1 influenza A virus-infected cells. Antiviral Res 97:41–48

    Article  CAS  PubMed  Google Scholar 

  21. Xu G, Dou J, Zhang L, Guo Q, Zhou C (2010) Inhibitory effects of baicalein on the influenza virus in vivo is determined by baicalin in the serum. Biol Pharm Bull 3:238–243

    Article  Google Scholar 

  22. Yu C, Yan Y, Wu X, Zhang B, Wang W, Wu Q (2010) Anti-influenza virus effects of the aqueous extract from Mosla scabra. J Ethnopharmacol 127:280–285

    Article  PubMed  Google Scholar 

  23. Tian L, Wang Z, Wu H, Wang S et al (2011) Evaluation of the anti-neuraminidase activity of the traditional Chinese medicines and determination of the anti-influenza A virus effects of the neuraminidase inhibitory TCMs in vitro and in vivo. J Ethnopharmacol 137:534–542

    Article  PubMed  Google Scholar 

  24. Saha RK, Takahashi T, Kurebayashi Y et al (2010) Antiviral effect of strictinin on influenza virus replication. Antiviral Res 88:10–18

    Article  CAS  PubMed  Google Scholar 

  25. Dou J, Chen L, Xu G, Zhang L, Zhou H, Wang H, Su Z, Ke M, Guo Q, Zhou C (2011) Effects of baicalein on Sendai virus in vivo are linked to serum baicalin and its inhibition of hemagglutinin-neuraminidase. Arch Virol 156:793–801

    Article  CAS  PubMed  Google Scholar 

  26. Su Z, Dou J, Xu Z, Gou Q, Zhou C (2012) A novel inhibitory mechanism of baicalein on influenza A/FM1/1/47 (H1N1) virus: interference with midlate mRNA synthesis in cell culture. Chin J Nat Med 10:0415–0420

    Article  CAS  Google Scholar 

  27. Yamanaka T, Bannai H, Nemoto M et al (2012) Efficacy of a single intravenous dose of the neuraminidase inhibitor peramivir in the treatment of equine influenza. Vet J 193:358–362

    Article  CAS  PubMed  Google Scholar 

  28. Bar-On Y, Glasner A, Meningher T et al (2013) Neuraminidase-mediated, NKp46-dependent immune-evasion mechanism of influenza viruses. Cell Rep 3:1044–1050

    Article  CAS  PubMed  Google Scholar 

  29. Barnard DL (2009) Animal models for the study of influenza pathogenesis and therapy. Antiviral Res 82:A110–A122

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This research was financially supported by a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), the Scientific and Technological Support & Social Development Plan of Jiangsu Province (BE2012743), the Fundamental Research Funds for the Central Universities (No. JKZY2013001, ZL2014SK0035), and Jiangsu Province Academic Scientific Research Industrialization Projects (JHB2012-6).

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Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People’s Republic of China

    Yue Ding, Jie Dou, Zaijin Teng, Jie Yu, Tingting Wang, Na Lu, Hui Wang & Changlin Zhou

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  1. Yue Ding
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  2. Jie Dou
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  3. Zaijin Teng
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  4. Jie Yu
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  6. Na Lu
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  7. Hui Wang
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  8. Changlin Zhou
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Correspondence to Changlin Zhou.

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Y. Ding and J. Dou contributed equally to this work.

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Ding, Y., Dou, J., Teng, Z. et al. Antiviral activity of baicalin against influenza A (H1N1/H3N2) virus in cell culture and in mice and its inhibition of neuraminidase. Arch Virol 159, 3269–3278 (2014). https://doi.org/10.1007/s00705-014-2192-2

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  • DOI: https://doi.org/10.1007/s00705-014-2192-2

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