Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3

  • Song, Jae-Hyoung (College of Pharmacy, Kangwon National University) ;
  • Choi, Hwa-Jung (Department of Beauty Science, Kwangju Women's University) ;
  • Song, Hyuk-Hwan (Natural Medicine Research Center, Korea Research Institute Bioscience and Biotechnology) ;
  • Hong, Eun-Hye (College of Pharmacy, Kangwon National University) ;
  • Lee, Bo-Ra (College of Pharmacy, Kangwon National University) ;
  • Oh, Sei-Ryang (Natural Medicine Research Center, Korea Research Institute Bioscience and Biotechnology) ;
  • Choi, Kwangman (Targeted Medicine Research Center, Korea Research Institute Bioscience and Biotechnology) ;
  • Yeo, Sang-Gu (Division of Vaccine Research, Center for Infectious Diseases, National Institute of Health, Korea Centers for Diseases Control and Prevention) ;
  • Lee, Yong-Pyo (Division of Vaccine Research, Center for Infectious Diseases, National Institute of Health, Korea Centers for Diseases Control and Prevention) ;
  • Cho, Sungchan (Targeted Medicine Research Center, Korea Research Institute Bioscience and Biotechnology) ;
  • Ko, Hyun-Jeong (College of Pharmacy, Kangwon National University)
  • Received : 2014.03.11
  • Accepted : 2014.04.10
  • Published : 2014.07.15
⟨ Previous Next ⟩

Abstract

Background: Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods: Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results: The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of $100{\mu}g/mL$. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at $100{\mu}g/mL$. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion: Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

Keywords

References

  1. Whitton JL, Cornell CT, Feuer R. Host and virus determinants of picornavirus pathogenesis and tropism. Nat Rev Microbiol 2005;3:765-76. https://doi.org/10.1038/nrmicro1284
  2. Chumakov M, Voroshilova M, Shindarov L, Lavrova I, Gracheva L, Koroleva G, Vasilenko S, Brodvarova I, Nikolova M, Gyurova S, et al. Enterovirus 71 isolated from cases of epidemic poliomyelitis-like disease in Bulgaria. Arch Virol 1979;60:329-40. https://doi.org/10.1007/BF01317504
  3. McMinn PC. An overview of the evolution of enterovirus 71 and its clinical and public health significance. FEMS Microbiol Rev 2002;6:91-107.
  4. Wang SM, Lei HY, Huang KJ, Wu JM, Wang JR, Yu CK, Su IJ, Liu CC. Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 2003;188:564-70. https://doi.org/10.1086/376998
  5. Song J, Yeo SG, Hong EH, Lee BR, Kim JW, Kim J, Jeong H, Kwon Y, Kim H, Lee S, et al. Antiviral activity of Hederasaponin B from Hedera helix against Enterovirus 71 subgenotypes C3 and C4a. Biomol Ther 2014;22:41-6. https://doi.org/10.4062/biomolther.2013.108
  6. Makela MJ, Puhakka T, Ruuskanen O, Leinonen M, Saikku P, Kimpimaki M, Blomqvist S, Hyypia T, Arstila P. Viruses and bacteria in the etiology of the common cold. J Clin Microbiol 1998;36:539-42.
  7. Zhu J, Message SD, Qiu Y, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, et al. Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma. Chest 2014;156:1219-29.
  8. Turner RB. The treatment of rhinovirus infections: progress and potential. Antiviral Res 2001;49:1-14. https://doi.org/10.1016/S0166-3542(00)00135-2
  9. Vlietinck AJ, Vanden Berghe DA. Can ethnopharmacology contribute to the development of antiviral drugs? J Ethnopharmacol 1991;32:141-53. https://doi.org/10.1016/0378-8741(91)90112-Q
  10. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev 1999;12:564-82.
  11. Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol 2000;124:507-14. https://doi.org/10.1104/pp.124.2.507
  12. Williams JE. Review of antiviral and immunomodulating properties of plants of the Peruvian rainforest with a particular emphasis on Una de Gato and Sangre de Grado. Altern Med Rev 2001;6:567-79.
  13. Jassim SA, Naji MA. Novel antiviral agents: a medicinal plant perspective. J Appl Microbiol 2003;95:412-27. https://doi.org/10.1046/j.1365-2672.2003.02026.x
  14. Fuzzati N. Analysis methods of ginsenosides. J Chromatogr B Analyt Technol Biomed Life Sci 2004;812:119-33. https://doi.org/10.1016/S1570-0232(04)00645-2
  15. Song X, Chen J, Sakwiwatkul K, Li R, Hu S. Enhancement of immune responses to influenza vaccine (H3N2) by ginsenoside Re. Int Immunopharmacol 2010;10:351-6. https://doi.org/10.1016/j.intimp.2009.12.009
  16. Peng D, Wang H, Qu C, Xie L, Wicks SM, Xie J. Ginsenoside Re: its chemistry, metabolism and pharmacokinetics. Chin Med 2012 Feb 7;7:2. https://doi.org/10.1186/1749-8546-7-2
  17. Chae S, Kang KA, Chang WY, Kim MJ, Lee SJ, Lee YS, Kim HS, Kim DH, Hyun JW. Effect of compound K, a metabolite of ginseng saponin, combined with gamma-ray radiation in human lung cancer cells in vitro and in vivo. J Agric Food Chem 2009;57:5777-82. https://doi.org/10.1021/jf900331g
  18. Cho WC, Chung WS, Lee SK, Leung AW, Cheng CH, Yue KK. Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur J Pharmacol 2006;550: 173-9. https://doi.org/10.1016/j.ejphar.2006.08.056
  19. Kim MS. Korean red ginseng tonic extends lifespan in D. melanogaster. Biomol Ther 2013;21:241-5. https://doi.org/10.4062/biomolther.2013.024
  20. Wang W, Rayburn ER, Hao M, Zhao Y, Hill DL, Zhang R, Wang H. Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides. Prostate 2008;68:809-19. https://doi.org/10.1002/pros.20742
  21. Lee MH, Lee BH, Jung JY, Cheon DS, Kim KT, Choi C. Antiviral effect of Korean red ginseng extract and ginsenosides on murine norovirus and feline calicivirus as surrogates for human norovirus. J Ginseng Res 2011;35: 429-35. https://doi.org/10.5142/jgr.2011.35.4.429
  22. Kang LJ, Choi YJ, Lee SG. Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication. Int J Biochem Cell Biol 2013;45:2612-21. https://doi.org/10.1016/j.biocel.2013.08.016
  23. Choi HJ, Kim JH, Lee CH, Ahn YJ, Song JH, Baek SH, Kwon DH. Antiviral activity of quercetin 7-rhamnoside against porcine epidemic diarrhea virus. Antiviral Res 2009;81:77-81. https://doi.org/10.1016/j.antiviral.2008.10.002
  24. Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16:S3-5. https://doi.org/10.3346/jkms.2001.16.S.S3
  25. Rivera E, Ekholm Pettersson F, Inganas M, Paulie S, Gronvik KO. The Rb1 fraction of ginseng elicits a balanced Th1 and Th2 immune response. Vaccine 2005;23:5411-9. https://doi.org/10.1016/j.vaccine.2005.04.007
  26. Yoo YC, Lee J, Park SR, Nam KY, Cho YH, Choi JE. Protective effect of ginsenoside-Rb2 from Korean red ginseng on the lethal infection of haemagglutinating virus of Japan in mice. J Ginseng Res 2013;37:80-6. https://doi.org/10.5142/jgr.2013.37.80
  27. Lee MH, Lee BH, Lee S, Choi C. Reduction of hepatitis A virus on FRhK-4 cells treated with Korean red ginseng extract and ginsenosides. J Food Sci 2013;78: M1412-5. https://doi.org/10.1111/1750-3841.12205
  28. Nakayama T, Urano T, Osano M, Hayashi Y, Sekine S, Ando T, Makinom S. Outbreak of herpangina associated with Coxsackievirus B3 infection. Pediatr Infect Dis J 1989;8:495-8. https://doi.org/10.1097/00006454-198908000-00004
  29. Graci JD, Cameron CE. Mechanisms of action of ribavirin against distinct viruses. Rev Med Virol 2006;16:37-48. https://doi.org/10.1002/rmv.483
  30. Choi HJ, Lim CH, Song JH, Baek SH, Kwon DH. Antiviral activity of raoulic acid from Raoulia australis against Picornaviruses. Phytomedicine 2009;16:35-9. https://doi.org/10.1016/j.phymed.2008.10.012
  31. Choi HJ, Song JH, Lim CH, Baek SH, Kwon DH. Anti-human rhinovirus activity of raoulic acid from Raoulia australis. J Med Food 2010;13:326-8. https://doi.org/10.1089/jmf.2009.1149
  32. Aquino R, De Simone F, Pizza C, Conti C, Stein ML. Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda. J Nat Prod 1989;52:679-85. https://doi.org/10.1021/np50064a002
  33. Aquino R, Conti C, De Simone F, Orsi N, Pizza C, Stein ML. Antiviral activity of constituents of Tamus communis. J Chemother 1991;3:305-9. https://doi.org/10.1080/1120009X.1991.11739110
  34. De Tommasi N, Conti C, Stein ML, Pizza C. Structure and in vitro antiviral activity of triterpenoid saponins from Calendula arvensis. Planta Med 1991;57: 250-3. https://doi.org/10.1055/s-2006-960084
  35. Weber ND, Andersen DO, North JA, Murray BK, Lawson LD, Hughes BG. In vitro virucidal effects of Allium sativum (garlic) extract and compounds. Planta Med 1992;58:417-23. https://doi.org/10.1055/s-2006-961504
  36. Denyer CV, Jackson P, Loakes DM, Ellis MR, Young DA. Isolation of antirhinoviral sesquiterpenes from ginger (Zingiber officinale). J Nat Prod 1994;57: 658-62. https://doi.org/10.1021/np50107a017
  37. Glatthaar-Saalmuller B, Sacher F, Esperester A. Antiviral activity of an extract derived from roots of Eleutherococcus senticosus. Antiviral Res 2001;50:223-8. https://doi.org/10.1016/S0166-3542(01)00143-7
  38. Pevear DC, Fancher MJ, Felock PJ, Rossmann MG, Miller MS, Diana G, Treasurywala AM, McKinlay MA, Dutko FJ. Conformational change in the floor of the human rhinovirus canyon blocks adsorption to HeLa cell receptors. J Virol 1989;63:2002-7.
  39. Zeichhardt H, Otto MJ, McKinlay MA, Willingmann P, Habermehl KO. Inhibition of poliovirus uncoating by disoxaril (WIN 51711). Virology 1987;160: 281-5. https://doi.org/10.1016/0042-6822(87)90075-4
  40. Fleischer R, Laessig K. Safety and efficacy evaluation of pleconaril for treatment of the common cold. Clin Infect Dis 2003;37:1722.
  41. Kim JH, Kang SA, Han SM, Shim I. Comparison of the antiobesity effects of the protopanaxadiol- and protopanaxatriol-type saponins of red ginseng. Phytother Res 2009;23:78-85. https://doi.org/10.1002/ptr.2561

Cited by

  1. Biotransformation of Ginsenosides Re and Rg1 by the Bacterium Microbacterium sp. GT35 vol.51, pp.1, 2014, https://doi.org/10.1007/s10600-015-1208-9
  2. Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses vol.2015, pp.None, 2014, https://doi.org/10.1155/2015/367250
  3. Bioassay-guided Isolation of Antiproliferative Triterpenoids from Euonymus alatus Twigs vol.10, pp.11, 2014, https://doi.org/10.1177/1934578x1501001131
  4. Antineuroinflammatory and Antiproliferative Activities of Constituents from Tilia amurensis vol.63, pp.10, 2014, https://doi.org/10.1248/cpb.c15-00393
  5. Anti-Enterovirus 71 Agents of Natural Products vol.20, pp.9, 2014, https://doi.org/10.3390/molecules200916320
  6. A new rearranged eudesmane sesquiterpene and bioactive sesquiterpenes from the twigs of Lindera glauca (Sieb. et Zucc.) Blume vol.39, pp.12, 2016, https://doi.org/10.1007/s12272-016-0838-1
  7. A New Monoacylglycerol from the Fruiting Bodies of Gymnopilus Spectabilis vol.40, pp.3, 2014, https://doi.org/10.3184/174751916x14546877525997
  8. Isolation, Purification and Quantification of Ginsenoside F 5 and F 3 Isomeric Compounds from Crude Extracts of Flower Buds of Panax ginseng vol.21, pp.3, 2014, https://doi.org/10.3390/molecules21030315
  9. The antimicrobial properties of ginseng and ginseng extracts vol.14, pp.1, 2014, https://doi.org/10.1586/14787210.2016.1118345
  10. Antiviral Activity of Oroxylin A against Coxsackievirus B3 Alleviates Virus-Induced Acute Pancreatic Damage in Mice vol.11, pp.5, 2014, https://doi.org/10.1371/journal.pone.0155784
  11. Lignans from the Twigs of Euonymus alatus (Thunb.) Siebold and Their Biological Evaluation vol.13, pp.10, 2014, https://doi.org/10.1002/cbdv.201600083
  12. Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection vol.40, pp.4, 2014, https://doi.org/10.1016/j.jgr.2015.09.002
  13. Antiviral activity of micafungin against enterovirus 71 vol.13, pp.1, 2014, https://doi.org/10.1186/s12985-016-0557-8
  14. Chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity vol.11, pp.None, 2014, https://doi.org/10.1186/s13020-016-0074-0
  15. Berberine Restricts Coxsackievirus B Type 3 Replication via Inhibition of c-Jun N-Terminal Kinase (JNK) and p38 MAPK Activation In Vitro vol.23, pp.None, 2014, https://doi.org/10.12659/msm.899804
  16. Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus vol.41, pp.4, 2017, https://doi.org/10.1016/j.jgr.2016.08.010
  17. A new naphthoquinone analogue and antiviral constituents from the root of Rhinacanthus nasutus vol.33, pp.3, 2014, https://doi.org/10.1080/14786419.2018.1452004
  18. Lignan Dimers from Forsythia viridissima Roots and Their Antiviral Effects vol.82, pp.2, 2019, https://doi.org/10.1021/acs.jnatprod.8b00590
  19. Simultaneous determination of seven sesquiterpene lactone glucosides in Ixeris dentata by high-performance liquid chromatography coupled with tandem mass spectrometry and their antiviral activities vol.31, pp.4, 2014, https://doi.org/10.1556/1326.2018.00470
  20. Phytochemicals: Potential Therapeutic Interventions Against Coronavirus-Associated Lung Injury vol.11, pp.None, 2020, https://doi.org/10.3389/fphar.2020.588467
  21. Inhibition of Herpes Simplex Viruses, Types 1 and 2, by Ginsenoside 20(S)-Rg3 vol.30, pp.1, 2020, https://doi.org/10.4014/jmb.1908.08047
  22. Hormesis and Ginseng: Ginseng Mixtures and Individual Constituents Commonly Display Hormesis Dose Responses, Especially for Neuroprotective Effects vol.25, pp.11, 2020, https://doi.org/10.3390/molecules25112719
  23. Current strategies against COVID-19 vol.15, pp.None, 2014, https://doi.org/10.1186/s13020-020-00353-7
  24. Pharmacological Efficacy of Ginseng against Respiratory Tract Infections vol.26, pp.13, 2014, https://doi.org/10.3390/molecules26134095
  25. Molecular scaffolds from mother nature as possible lead compounds in drug design and discovery against coronaviruses: A landscape analysis of published literature and molecular docking studies vol.157, pp.None, 2021, https://doi.org/10.1016/j.micpath.2021.104933
  26. Nanoformulation Composed of Ellagic Acid and Functionalized Zinc Oxide Nanoparticles Inactivates DNA and RNA Viruses vol.13, pp.12, 2014, https://doi.org/10.3390/pharmaceutics13122174