Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus

  • Received : 2016.05.04
  • Accepted : 2016.08.25
  • Published : 2017.10.15
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Abstract

Background: Ginsenosides are the major components of Panax ginseng Meyer, an herbal medicine used for the treatment of various diseases. Different ginsenosides contribute to the biological properties of ginseng, such as antimicrobial, anticancer, and immunomodulatory properties. In this study, we investigated the antiviral effects of 15 ginsenosides and compound K on gammaherpesvirus. Methods: The antiviral activity of ginsenosides was examined using the plaque-forming assay and by analyzing the expression of the lytic gene. Results: 20(R)-Ginsenoside Rh2 inhibited the replication and proliferation of murine gammaherpesvirus 68 (MHV-68), and its half-maximal inhibitory concentration ($IC_{50} $) against MHV-68 was estimated to be $2.77{\mu}M$. In addition, 20(R)-ginsenoside Rh2 inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpesvirus in the Kaposi's sarcoma-associated herpesvirus (KSHV)-positive cell line BC3. Conclusion: Our results indicate that 20(R)-ginsenoside Rh2 can inhibit the replication of mouse and human gammaherpesviruses, and thus, has the potential to treat gammaherpesvirus infection.

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References

  1. 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
  2. Jin SH, Park JK, Nam KY, Park SN, Jung NP. Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol 1999;66:123-9. https://doi.org/10.1016/S0378-8741(98)00190-1
  3. Surh YJ, Ferguson LR. Dietary and medicinal antimutagens and anticarcinogens: molecular mechanisms and chemopreventive potentialehighlights of a symposium. Mutat Res 2003;523-524:1-8. https://doi.org/10.1016/S0027-5107(02)00343-3
  4. Jeon C, Kang S, Park S, Lim K, Hwang KW, Min H. T cell stimulatory effects of Korean Red Ginseng through modulation of myeloid-derived suppressor cells. J Ginseng Res 2011;35:462-70. https://doi.org/10.5142/jgr.2011.35.4.462
  5. Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev 2004;9:259-74.
  6. Lim DS, Bae KG, Jung IS, Kim CH, Yun YS, Song JY. Anti-septicaemic effect of polysaccharide from Panax ginseng by macrophage activation. J Infect 2002;45:32-8. https://doi.org/10.1053/jinf.2002.1007
  7. Kang S, Min H. Ginseng, the 'Immunity Boost': the effects of Panax ginseng on immune system. J Ginseng Res 2012;36:354-68. https://doi.org/10.5142/jgr.2012.36.4.354
  8. Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW. Biological activities of conjugated fatty acids: conjugated eicosadienoic (conj. 20:2delta(c11,t13/t12,c14)), eicosatrienoic (conj. 20:3delta(c8,t12,c14)), and heneicosadienoic (conj. 21:2delta(c12,t14/c13,t15)) acids and other metabolites of conjugated linoleic acid. Biochim Biophys Acta 2005;1687:120-9. https://doi.org/10.1016/j.bbalip.2004.11.010
  9. Song JH, Choi HJ, Song HH, Hong EH, Lee BR, Oh SR, Choi K, Yeo SG, Lee YP, Cho S, et al. Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3. J Ginseng Res 2014;38:173-9. https://doi.org/10.1016/j.jgr.2014.04.003
  10. Kang KA, Piao MJ, Kim KC, Zheng J, Yao CW, Cha JW, Kim HS, Kim DH, Bae SC, Hyun JW. Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell growth and induces apoptosis through inhibition of histone deacetylase activity. Int J Oncol 2013;43:1907-14. https://doi.org/10.3892/ijo.2013.2129
  11. Kim AD, Kang KA, Kim HS, Kim DH, Choi YH, Lee SJ, Hyun JW. A ginseng metabolite, compound K, induces autophagy and apoptosis via generation of reactive oxygen species and activation of JNK in human colon cancer cells. Cell Death Dis 2013;4:e750. https://doi.org/10.1038/cddis.2013.273
  12. Saw CLL, Yang AYQ, Cheng DC, Boyanapalli SSS, Su ZY, Khor TO, Gao S, Wang JR, Jiang ZH, Kong ANT. Pharmacodynamics of ginsenosides: antioxidant activities, activation of Nrf2, and potential synergistic effects of combinations. Chem Res Toxicol 2012;25:1574-80. https://doi.org/10.1021/tx2005025
  13. Rickabaugh TM, Brown HJ, Wu TT, Song MJ, Hwang S, Deng H, Mitsouras K, Sun R. Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 RTA reactivates murine gammaherpesvirus 68 from latency. J Virol 2005;79:3217-22. https://doi.org/10.1128/JVI.79.5.3217-3222.2005
  14. Steed AL, Barton ES, Tibbetts SA, Popkin DL, Lutzke ML, Rochford R, Virgin 4th HW. Gamma interferon blocks gammaherpesvirus reactivation from latency. J Virol 2006;80:192-200. https://doi.org/10.1128/JVI.80.1.192-200.2006
  15. Du MQ, Diss TC, Liu H, Ye H, Hamoudi RA, Cabecadas J, Dong HY, Harris NL, Chan JK, Rees JW, et al. KSHV- and EBV-associated germinotropic lymphoproliferative disorder. Blood 2002;100:3415-8. https://doi.org/10.1182/blood-2002-02-0487
  16. Cesarman E, Moore PS, Rao PH, Inghirami G, Knowles DM, Chang Y. In vitro establishment and characterization of two acquired immunodeficiency syndrome-related lymphoma cell lines (BC-1 and BC-2) containing Kaposi's sarcoma-associated herpesvirus-like (KSHV) DNA sequences. Blood 1995;86:2708-14.
  17. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 1994;266:1865-9. https://doi.org/10.1126/science.7997879
  18. Soulier J, Grollet L, Oksenhendler E, Cacoub P, Cazals-Hatem D, Babinet P, d'Agay MF, Clauvel JP, Raphael M, Degos L, et al. Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease. Blood 1995;86:1276-80.
  19. Brooks L, Yao QY, Rickinson AB, Young LS. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts. J Virol 1992;66:2689-97.
  20. Iizasa H, Nanbo A, Nishikawa J, Jinushi M, Yoshiyama H. Epstein-Barr Virus (EBV)-associated gastric carcinoma. Viruses 2012;4:3420-39. https://doi.org/10.3390/v4123420
  21. Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. Blood 2011;118:4041-52. https://doi.org/10.1182/blood-2011-03-278127
  22. Zhou F, Xue M, Qin D, Zhu X, Wang C, Zhu J, Hao T, Cheng L, Chen X, Bai Z, et al. HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3beta signaling pathway. PLoS One 2013;8:e53145. https://doi.org/10.1371/journal.pone.0053145
  23. Cho HJ, Jeong SG, Park JE, Han JA, Kang HR, Lee D, Song MJ. Antiviral activity of angelicin against gammaherpesviruses. Antiviral Res 2013;100:75-83. https://doi.org/10.1016/j.antiviral.2013.07.009
  24. Simas JP, Efstathiou S. Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol 1998;6:276-82. https://doi.org/10.1016/S0966-842X(98)01306-7
  25. Wu TT, Tong LM, Rickabaugh T, Speck S, Sun R. Function of Rta is essential for lytic replication of murine gammaherpesvirus 68. J Virol 2001;75:9262-73. https://doi.org/10.1128/JVI.75.19.9262-9273.2001
  26. Im K, Lee JY, Byeon H, Hwang KW, Kang W, Whang WK, Min H. In Vitro antioxidative and anti-inflammatory activities of the ethanol extract of eggplant (Solanum melongena) stalks in macrophage RAW 264.7 cells. Food Agric Immunol 2016;27:758-71. https://doi.org/10.1080/09540105.2016.1150427
  27. Lee KP, Kang S, Noh MS, Park SJ, Kim JM, Chung HY, Je NK, Lee YG, Choi YW, Im DS. Therapeutic effects of s-petasin on disease models of asthma and peritonitis. Biomol Ther 2015;23:45-52. https://doi.org/10.4062/biomolther.2014.069
  28. 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
  29. Lee MH, Seo DJ, Kang JH, Oh SH, Choi C. Expression of antiviral cytokines in Crandell-Reese feline kidney cells pretreated with Korean red ginseng extract or ginsenosides. Food Chem Toxicol 2014;70:19-25. https://doi.org/10.1016/j.fct.2014.04.034
  30. Liang YY, Wang B, Qian DM, Li L, Wang ZH, Hu M, Song XX. Inhibitory effects of Ginsenoside Rb1 on apoptosis caused by HSV-1 in human glioma cells. Virol Sin 2012;27:19-25. https://doi.org/10.1007/s12250-012-3220-6
  31. 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
  32. Liu J, Shiono J, Shimizu K, Yu H, Zhang C, Jin F, Kondo R. 20(R)-ginsenoside Rh2, not 20(S), is a selective osteoclastgenesis inhibitor without any cytotoxicity. Bioorg Med Chem Lett 2009;19:3320-3. https://doi.org/10.1016/j.bmcl.2009.04.054
  33. Wang Z, Zheng Q, Liu K, Li G, Zheng R. Ginsenoside Rh(2) enhances antitumour activity and decreases genotoxic effect of cyclophosphamide. Basic Clin Pharmacol Toxicol 2006;98:411-5. https://doi.org/10.1111/j.1742-7843.2006.pto_348.x
  34. Bae EA, Han MJ, Kim EJ, Kim DH. Transformation of ginseng saponins to ginsenoside Rh2 by acids and human intestinal bacteria and biological activities of their transformants. Arch Pharm Res 2004;27:61-7. https://doi.org/10.1007/BF02980048
  35. Bae EA, Han MJ, Choo MK, Park SY, Kim DH. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002;25:58-63. https://doi.org/10.1248/bpb.25.58
  36. Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001;16(Suppl.):S28-37. https://doi.org/10.3346/jkms.2001.16.S.S28
  37. Oh M, Choi YH, Choi S, Chung H, Kim K, Kim SI, Kim DK, Kim ND. Anti-proliferating effects of ginsenoside Rh2 on MCF-7 human breast cancer cells. Int J Oncol 1999;14:869-75.
  38. Choi WY, Lim HW, Lim CJ. Anti-inflammatory, antioxidative and matrix metalloproteinase inhibitory properties of 20(R)-ginsenoside Rh2 in cultured macrophages and keratinocytes. J Pharm Pharmacol 2013;65:310-6. https://doi.org/10.1111/j.2042-7158.2012.01598.x
  39. Park EK, Choo MK, Kim EJ, Han MJ, Kim DH. Antiallergic activity of ginsenoside Rh2. Biol Pharm Bull 2003;26:1581-4. https://doi.org/10.1248/bpb.26.1581
  40. Lingel A, Ehlers E, Wang Q, Cao M, Wood C, Lin R, Zhang L. Kaposi's sarcoma-associated herpesvirus reduces cellular myeloid differentiation primary-response gene 88 (MyD88) expression via modulation of its RNA. J Virol 2016;90:180-8. https://doi.org/10.1128/JVI.02342-15
  41. Qi XD, Hou JC, Yu HT, Zhang CJ. 20 (S)-Ginsenoside-Rh2 and 20 (R)-Ginsenoside-Rh2 activate IkappaB phosphorylation expression in human lung adenocarcinoma A549 cells. Adv Mat Res 2011;268-270:1205-10. https://doi.org/10.4028/www.scientific.net/AMR.268-270.1205

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