The Potential Inhibitory Effect of Sambucus Nigra Fruit on Early Replication of Influenza Virus

Document Type : Original Article (s)

Authors

1 Department of Agricultural Biotechnology, Payame Noor University, Tehran, Iran

2 Assistant Professor, Razi Vaccine and Serum Research Institute, Karaj, Iran

3 Associate Professor, Department of Agricultural Biotechnology, Payame Noor University, Tehran, Iran

Abstract

Background: Influenza is considered as a serious threat to human and animal health worldwide. In recent years, with the rise of drug-resistant strains, antiviral property of herb natural components with fewer side effects is of great importance. In this study, the potential antiviral activity of Sambucus nigra fruit was evaluated in human epithelium cell (A549) cultures infected with influenza virus.Methods: The aqueous extract of Sambucus nigra fruit was prepared and the cytotoxic concentration of the extract on A549 cells was determined. Subsequently, the 50 percent inhibitory concentration (IC50) of various herbal extract concentrations for inhibiting the replication of influenza virus and the selective index (SI) were assessed following pre-treatment (before the virus attachment to cells or direct effect) and post-treatment (after virus absorption to cells or indirect effect) procedures. Inhibitory effect of the herb on virus replication was examined via using virus titration and quantitative real time reverse transcription polymerase chain reaction (real time RT-PCR).Findings: The concentration of 82.6 μg/ml was the threshold dose of the substance that did not cause a cytotoxic effect against the cells. The estimated selective index of the extract before cellular attachment (15.10 μg/ml), increased viral titer as well as synthesized viral nucleoprotein RNAs indicating that the herb had no direct inhibitory effects on viral hemagglutinin activity. In post-treatment, the higher estimated selective index, a significant decrease was seen in virus titer and viral nucleoprotein copy numbers confirming that the herb inhibited virion budding and release activities.Conclusion: The results suggest that Sambucus nigra treatment of the influenza virus infected-human epithelial cells may affect either inhibition of virus particle release or involving in cellular lipid raft function. Mechanism of this interaction will be investigated in future studies.

Keywords

References

  1. Butt KM, Smith GJ, Chen H, Zhang LJ, Leung YH, Xu KM, et al. Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol 2005; 43(11): 5760-7.
  2. Russell CJ, Webster RG. The genesis of a pandemic influenza virus. Cell 2005; 123(3): 368-71.
  3. Wright PF, Neumann G, Kawaoka Y. Orthomyxoviruses. In: Fields B N, Knipe DM, Howley PM, editors. Fields virology. Philadelphia, PA: Lippincott Williams and Wilkins; 2007. P. 1961-740.
  4. Shahsavandi Sh. A review: evaluating the dynamics of influenza viruses replication and host cell- virus interactions. J Arak Univ Med Sci 2015; 18(5): 1-20. [In Persian].
  5. Ong AK, Hayden FG. John F. Enders lecture 2006: antivirals for influenza. J Infect Dis 2007; 196(2): 181-90.
  6. Cheung CL, Rayner JM, Smith GJ, Wang P, Naipospos TS, Zhang J, et al. Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis 2006; 193(12): 1626-9.
  7. Kiso M, Mitamura K, Sakai-Tagawa Y, Shiraishi K, Kawakami C, Kimura K, et al. Resistant influenza A viruses in children treated with oseltamivir: descriptive study. Lancet 2004; 364(9436): 759-65.
  8. Triana-Baltzer GB, Babizki M, Chan MC, Wong AC, Aschenbrenner LM, Campbell ER, et al. DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis. J Antimicrob Chemother 2010; 65(2): 275-84.
  9. Furuta Y, Takahashi K, Shiraki K, Sakamoto K, Smee DF, Barnard DL, et al. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res 2009; 82(3): 95-102.
  10. Malakhov MP, Aschenbrenner LM, Smee DF, Wandersee MK, Sidwell RW, Gubareva LV, et al. Sialidase fusion protein as a novel broad-spectrum inhibitor of influenza virus infection. Antimicrob Agents Chemother 2006; 50(4): 1470-9.
  11. Eyer L, Hruska K. Antiviral agents targeting the influenza virus: a review and publication analysis. Vet Med 2015; 58(3): 113-85.
  12. Pinto R, Herold S, Cakarova L, Hoegner K, Lohmeyer J, Planz O, et al. 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(1): 45-56.
  13. European Medicine Agency. Science Medicine Health. Assessment report on Sambucus nigra L., fructus. EMA/HMPC/44208/2012. Committee on Herbal Medicinal Products (HMPC) [Online]. [cited 2013 Mar 12]; Available from: URL: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_ assessment _report/2013/04/WC500142245.pdf.
  14. Shahsavandi S, Ebrahimi MM. Influenza. Tehran, Iran: Iranian Student Book Agency; 2013. [In Persian].
  15. Zarrin Lebas N, Shahsavandi S, Mohammadi A, Ebrahimi MM, Bakhshesh M. Replication efficiency of influenza a virus H9N2: A comparative analysis between different origin cell types. Jundishapur J Microbiol 2013; 6(9): e8584.
  16. Shahsavandi S, Ebrahimi MM, Sadeghi K, Mosavi SZ, Mohammadi A. Dose- and time-dependent apoptosis induced by avian H9N2 influenza virus in human cells. Biomed Res Int 2013; 2013: 524165.
  17. Shahsavandi S. Virus genetic variations and evade from immune system, the present influenza challenges: review article. Tehran Univ Med J 2015; 73(7): 469-77. [In Persian].
  18. Zakay-Rones Z, Thom E, Wollan T, Wadstein J. Randomized study of the efficacy and safety of oral elderberry extract in the treatment of influenza A and B virus infections. J Int Med Res 2004; 32(2): 132-40.
  19. Roschek B, Jr., Fink RC, McMichael MD, Li D, Alberte RS. Elderberry flavonoids bind to and prevent H1N1 infection in vitro. Phytochemistry 2009; 70(10): 1255-61.
  20. Hudson JB. The use of herbal extracts in the control of influenza. J Med Plants Res 2009; 3(13): 1189-95.
  21. Wang X, Jia W, Zhao A, Wang X. Anti-influenza agents from plants and traditional Chinese medicine. Phytother Res 2006; 20(5): 335-41.
  22. 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(15): 7141-7.
  23. Lee CL, Chiang LC, Cheng LH, Liaw CC, Abd El-Razek MH, Chang FR, et al. Influenza A (H(1)N(1)) Antiviral and Cytotoxic Agents from Ferula assa-foetida. J Nat Prod 2009; 72(9): 1568-72.
  24. Song JM, Lee KH, Seong BL. Antiviral effect of catechins in green tea on influenza virus. Antiviral Res 2005; 68(2): 66-74.
  25. Ketabchi S, Moatari A, Shadram M, Rostami Y. The anti influenza virus activity of Anchusa Italica. Asian J Exp Biol Sci 2011; 2(4): 758-61.
  26. Kwon HJ, Kim HH, Yoon SY, Ryu YB, Chang JS, Cho KO, et al. In vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination. Virol J 2010; 7: 307.
  27. Sawai R, Kuroda K, Shibata T, Gomyou R, Osawa K, Shimizu K. Anti-influenza virus activity of Chaenomeles sinensis. J Ethnopharmacol 2008; 118(1): 108-12.
  28. He W, Han H, Wang W, Gao B. Anti-influenza virus effect of aqueous extracts from dandelion. Virol J 2011; 8: 538.
  29. Vlachojannis JE, Cameron M, Chrubasik S. A systematic review on the sambuci fructus effect and efficacy profiles. Phytother Res 2010; 24(1): 1-8.
  30. Suzuki T, Suzuki Y. Virus infection and lipid rafts. Biol Pharm Bull 2006; 29(8): 1538-41.
  31. Takahashi T, Suzuki T. Function of membrane rafts in viral lifecycles and host cellular response. Biochem Res Int 2011; 2011: 245090.
Journal of Isfahan Medical School
Volume 33, Issue 352 - Serial Number 352
July and August 2015
Pages 1607-1617

Files

History

  • Receive Date: 08 June 2015
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

Share

How to cite

Statistics