Skip to main content

Advertisement

SpringerLink
Log in

Antiherpes evaluation of soybean isoflavonoids

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

The antiviral effects of soybean isoflavonoids have been investigated recently, especially those of genistein. It has been reported that this isoflavone is able to inhibit herpes simplex virus (HSV) replication, which is associated with skin and epithelial mucosa infections. The treatment of these infections with antiherpes drugs has resulted in the emergence of resistant viral strains. Based on this evidence, the aim of this study was to investigate the anti-HSV effects of soybean isoflavonoids: daidzein, genistein, glycitein, and coumestrol. Genistein and coumestrol inhibited HSV-1 (KOS and 29R strains, which are acyclovir sensitive and acyclovir resistant, respectively) and HSV-2 (333 strain) replication, whereas no antiviral effects were detected for daidzein and glycitein. The mechanisms of action were evaluated by different methodological strategies. Coumestrol affected the early stages of viral infection, and both compounds were able to reduce HSV-1 protein expression, as well as HSV-2 cell-to-cell spread.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cornwell T, Cohick W, Raskin I (2004) Dietary phytoestrogens and health. Phytochemistry 65:995–1016. doi:10.1016/j.phytochem.2004.03.005

    Article  CAS  PubMed  Google Scholar 

  2. Gaete L, Tchernitchin AN, Bustamante R, Villena J, Lemus I, Gidekel M, Cabrera G, Carrillo O (2011) Genistein selectively inhibits estrogen-induced cell proliferation and other responses to hormone stimulation in the prepubertal rat uterus. J Med Food 14:1597–1603. doi:10.1089/jmf.2010.0349

    Article  CAS  PubMed  Google Scholar 

  3. Lagari VS, Levis S (2014) Phytoestrogens for menopausal bone loss and climacteric symptoms. J Steroid Biochem Mol Biol 139:294–301. doi:10.1016/j.jsbmb.2012.12.002

    Article  CAS  PubMed  Google Scholar 

  4. Nadal-Serrano M, Pons DG, Sastre-Serra J, MeM Blanquer-Rosselló, Roca P, Oliver J (2013) Genistein modulates oxidative stress in breast cancer cell lines according to ERα/ERβ ratio: effects on mitochondrial functionality, sirtuins, uncoupling protein 2 and antioxidant enzymes. Int J Biochem Cell Biol 45:2045–2051. doi:10.1016/j.biocel.2013.07.002

    Article  CAS  PubMed  Google Scholar 

  5. Pavese JM, Farmer RL, Bergan RC (2010) Inhibition of cancer cell invasion and metastasis by genistein. Cancer Metastasis Rev 29:465–482. doi:10.1007/s10555-010-9238-z

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Nagaraju GP, Zafar SF, El-Rayes BF (2013) Pleiotropic effects of genistein in metabolic, inflammatory, and malignant diseases. Nutr Rev 71:562–572. doi:10.1111/nure.12044

    Article  PubMed  Google Scholar 

  7. Zhang W, Zhang H, Wang N, Zhao C, Deng F, Wu N, He Y, Chen X, Zhang J, Wen S, Liao Z, Zhang Q, Zhang Z, Liu W, Yan Z, Luu HH, Haydon RC, Zhou L, He TC (2013) Modulation of β-catenin signaling by the inhibitors of MAP kinase, tyrosine kinase, and PI3-kinase pathways. Int J Med Sci 10:1888–1898. doi:10.7150/ijms.6019

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Lee S-O, Renouf M, Ye Z, Murphy PA, Hendrich S (2007) Isoflavone glycitein diminished plasma cholesterol in female golden Syrian hamsters. J Agric Food Chem 55:11063–11067. doi:10.1021/jf070972r

    Article  CAS  PubMed  Google Scholar 

  9. Aras AB, Guven M, Akman T, Ozkan A, Sen HM, Duz U, Kalkan Y, Silan C, Cosar M (2015) Neuroprotective effects of daidzein on focal cerebral ischemia injury in rats. Neural Regen Res 1:146–152

    Article  Google Scholar 

  10. Argenta DF, Franco C, Koester LS, Bassani VL, Teixeira HF (2011) LC analysis of coumestrol incorporated into topical lipid nanoemulsions. Pharmazie 66:929–932. doi:10.1691/ph.2011.1076

    CAS  PubMed  Google Scholar 

  11. Liu S, Hsieh D, Yang YL, Xu Z, Peto C, Jablons DM, You L (2013) Coumestrol from the national cancer Institute’s natural product library is a novel inhibitor of protein kinase CK2. BMC Pharmacol Toxicol 14:36. doi:10.1186/2050-6511-14-36

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Seo DB, Jeong HW, Lee SJ (2014) Coumestrol induces mitochondrial biogenesis by activating Sirt1 in cultured skeletal muscle cells. J Agric Food Chem 62:4298–4305. doi:10.1021/jf404882w

    Article  CAS  PubMed  Google Scholar 

  13. Fang H, Tong W, Branham WS, Moland CL, Dial SL, Hong H, Xie Q, Perkins R, Owens W, Sheehan DM (2003) Study of 202 natural, synthetic, and environmental chemicals for binding to the androgen receptor. Chem Res Toxicol 16:1338–1358. doi:10.1021/tx030011g

    Article  CAS  PubMed  Google Scholar 

  14. Cho SY, Cho S, Park E, Kim B, Sohn EJ, Oh B, Lee EO, Lee HJ, Kim SH (2014) Coumestrol suppresses hypoxia inducible factor 1α by inhibiting ROS mediated sphingosine kinase 1 in hypoxic PC-3 prostate cancer cells. Bioorg Med Chem Lett 24:2560–2564. doi:10.1016/j.bmcl.2014.03.084

    Article  CAS  PubMed  Google Scholar 

  15. Lee YH, Yuk HJ, Park KH, Bae YS (2013) Coumestrol induces senescence through protein kinase CKII inhibition-mediated reactive oxygen species production in human breast cancer and colon cancer cells. Food Chem 141:381–388. doi:10.1016/j.foodchem.2013.03.053

    Article  CAS  PubMed  Google Scholar 

  16. Akula SM, Hurley DJ, Wixon RL, Wang C, Chase CC (2002) Effect of genistein on replication of bovine herpesvirus type 1. Am J Vet Res 63:1124–1128. doi:10.2460/ajvr.2002.63.1124

    Article  CAS  PubMed  Google Scholar 

  17. Kolokoltsov AA, Adhikary S, Garver J, Johnson L, Davey RA, Vela EM (2012) Inhibition of Lassa virus and Ebola virus infection in host cells treated with the kinase inhibitors genistein and tyrphostin. Arch Virol 157:121–127. doi:10.1007/s00705-011-1115-8

    Article  CAS  PubMed  Google Scholar 

  18. Vela EM, Bowick GC, Herzog NK, Aronson JF (2008) Genistein treatment of cells inhibits arenavirus infection. Antiviral Res 77:153–156. doi:10.1016/j.antiviral.2007.09.005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Yura Y, Yoshida H, Sato M (1993) Inhibition of herpes simplex virus replication by genistein, an inhibitor of protein-tyrosine kinase. Arch Virol 132:451–461. doi:10.1007/BF01309554

    Article  CAS  PubMed  Google Scholar 

  20. Lyu SY, Rhim JY, Park WB (2005) Antiherpetic activities of flavonoids against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro. Arch Pharm Res 28:1293–1301. doi:10.1007/BF02978215

    Article  CAS  PubMed  Google Scholar 

  21. Argenta DF, de Mattos CB, Misturini FD, Koester LS, Bassani VL, Simões CM, Teixeira HF (2014) Factorial design applied to the optimization of lipid composition of topical antiherpetic nanoemulsions containing isoflavone genistein. Int J Nanomedicine 9:4737–4747. doi:10.2147/IJN.S67732

    PubMed Central  PubMed  Google Scholar 

  22. Coleman JL, Shukla D (2013) Recent advances in vaccine development for herpes simplex virus types I and II. Hum Vaccin Immunother 9:729–735. doi:10.4161/hv.23289

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Brady RC, Bernstein DI (2004) Treatment of herpes simplex virus infections. Antiviral Res 61:73–81. doi:10.1016/j.antiviral.2003.09.006

    Article  CAS  PubMed  Google Scholar 

  24. Vere Hodge RA, Field HJ (2013) Chapter one—antiviral agents for herpes simplex virus. In: De Erik C (ed) Advances in pharmacology. Academic Press, Dublin, pp 1–38

    Google Scholar 

  25. Burleson RC, Chambers TM, Wiedbrauk DL (1992) Virology. A Laboratory Manual, San Diego

    Google Scholar 

  26. Vichai V, Kirtikara K (2006) Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc 1:1112–1116. doi:10.1038/nprot.2006.179

    Article  CAS  PubMed  Google Scholar 

  27. Silva IT, Costa GM, Stoco PH, Schenkel EP, Reginatto FH, Simões CM (2010) In vitro antiherpes effects of a C-glycosylflavonoid-enriched fraction of Cecropia glaziovii Sneth. Lett Appl Microbiol 51:143–148. doi:10.1111/j.1472-765X.2010.02870.x

    CAS  PubMed  Google Scholar 

  28. Bertol JW, Rigotto C, de Pádua RM, Kreis W, Barardi CR, Braga FC, Simões CM (2011) Antiherpes activity of glucoevatromonoside, a cardenolide isolated from a Brazilian cultivar of Digitalis lanata. Antiviral Res 92:73–80. doi:10.1016/j.antiviral.2011.06.015

    Article  CAS  PubMed  Google Scholar 

  29. Cardozo FT, Camelini CM, Mascarello A, Rossi MJ, Nunes RJ, Barardi CR, de Mendonça MM, Simões CM (2011) Antiherpetic activity of a sulfated polysaccharide from Agaricus brasiliensis mycelia. Antiviral Res 92:108–114. doi:10.1016/j.antiviral.2011.07.009

    Article  CAS  PubMed  Google Scholar 

  30. Alvarez AL, Melon S, Dalton KP, Nicieza I, Roque A, Suarez B, Parra F (2013) Apple pomace, a by-product from the Asturian cider industry, inhibits herpes simplex virus types 1 and 2 in vitro replication: study of its mechanisms of action. J Med Food. doi:10.1089/jmf.2011.0308

    Google Scholar 

  31. Qie L, Marcellino D, Herold BC (1999) Herpes simplex virus entry is associated with tyrosine phosphorylation of cellular proteins. Virology 256:220–227. doi:10.1006/viro.1999.9673

    Article  CAS  PubMed  Google Scholar 

  32. Trybala E, Liljeqvist J-Å, Svennerholm B, Bergstrom T (2000) Herpes simplex virus types 1 and 2 differ in their interaction with heparan sulfate. J. Virol 74:9106–9114

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Tan WC, Jaganath IB, Manikam R, Sekaran SD (2013) evaluation of antiviral activities of four local Malaysian Phyllanthus species against Herpes simplex viruses and possible antiviral target. Int J Med Sci 13:1817–1829. doi:10.7150/ijms.6902

    Article  Google Scholar 

  34. Whitley RJ, Roizman B (2001) Herpes simplex virus infections. Lancet 357:1513–1518. doi:10.1016/S0140-6736(00)04638-9

    Article  CAS  PubMed  Google Scholar 

  35. Fontaine-Rodriguez EC, Knipe DM (2008) Herpes simplex virus ICP27 increases translation of a subset of viral late mRNAs. J Virol 82:3538–3545. doi:10.1128/JVI.02395-07

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Sattentau Q (2008) Avoiding the void: cell-to-cell spread of human viruses. Nat Rev Microbiol 6:815–826. doi:10.1038/nrmicro1972

    Article  CAS  PubMed  Google Scholar 

  37. Guo J, Xu X, Rasheed TK, Yoder A, Yu D, Liang H, Yi F, Hawley T, Jin T, Ling B, Wu Y (2013) Genistein interferes with SDF-1- and HIV-mediated actin dynamics and inhibits HIV infection of resting CD4 T cells. Retrovirology 10:62. doi:10.1186/1742-4690-10-62

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Ito S, Igishi T, Takata M, Ueda Y, Matsumoto S, Kodani M, Takeda K, Izumi H, Sakamoto T, Yamaguchi K, Makino H, Touge H, Chikumi H, Shimizu E (2014) Synergistic cell growth inhibition by the combination of amrubicin and Akt-suppressing agents in K-ras mutation-harboring lung adenocarcinoma cells: implication of EGFR tyrosine kinase inhibitors. Int J Oncol 44:685–692. doi:10.3892/ijo.2014.2249

    CAS  PubMed  Google Scholar 

  39. Qian HY, Zhang DG, Wang HW, Pei DS, Zheng JN (2014) Tyrosine phosphorylation of β-catenin affects its subcellular localization and transcriptional activity of β-catenin in Hela and Bcap-37 cells. Bioorg Med Chem Lett 24:2565–2570. doi:10.1016/j.bmcl.2014.03.078

    Article  CAS  PubMed  Google Scholar 

  40. Baird A, Florkiewicz RZ, Maher PA, Kaner RJ, Hajjar DP (1990) Mediation of virion penetration into vascular cells by association of basic fibroblast growth factor with herpes simplex virus type 1. Nature 348:344–346. doi:10.1038/348344a0

    Article  CAS  PubMed  Google Scholar 

  41. Ma Y, He B (2014) Recognition of herpes simplex viruses: toll-like receptors and beyond. J Mol Biol 426:1133–1147. doi:10.1016/j.jmb.2013.11.012

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Hull CM, Levin MJ, Tyring SK, Spruance SL (2014) Novel composite efficacy measure to demonstrate the rationale and efficacy of combination antiviral-anti-inflammatory treatment for recurrent herpes simplex labialis. Antimicrob Agents Chemother 58:1273–1278. doi:10.1128/AAC.02150-13

    Article  PubMed Central  PubMed  Google Scholar 

  43. Jantaratnotai N, Utaisincharoen P, Sanvarinda P, Thampithak A, Sanvarinda Y (2013) Phytoestrogens mediated anti-inflammatory effect through suppression of IRF-1 and pSTAT1 expressions in lipopolysaccharide-activated microglia. Int Immunopharmacol 17:483–488. doi:10.1016/j.intimp.2013.07.013

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES) - Rede Nanobiotec-Brazil (grant number 902/2009) and the State Foundation FAPERGS – PRONEM (grant number 11/2206-7).

Author information

Authors and Affiliations

  1. Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga 2752, Porto Alegre, 90610-000, Brazil

    D. F. Argenta, V. L. Bassani, L. S. Koester & H. F. Teixeira

  2. Programa de Pós-graduação em Farmácia, Universidade Federal de Santa Catarina (UFSC), Campus Trindade, Florianópolis, 88040-970, Brazil

    D. F. Argenta, I. T. Silva & C. M. O. Simões

Authors
  1. D. F. Argenta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. T. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V. L. Bassani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. S. Koester
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. F. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. M. O. Simões
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C. M. O. Simões.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Argenta, D.F., Silva, I.T., Bassani, V.L. et al. Antiherpes evaluation of soybean isoflavonoids. Arch Virol 160, 2335–2342 (2015). https://doi.org/10.1007/s00705-015-2514-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-015-2514-z

Keywords

Search

Navigation