DOI QR코드

DOI QR Code

Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean Red Ginseng Prevent Rotavirus Infection in Newborn Mice

  • Yang, Hui (Department of Microbiology, College of Medicine, Konyang University) ;
  • Oh, Kwang-Hoon (Department of Physical Education, College of Education, Kongju National University) ;
  • Kim, Hyun Jin (Department of Microbiology, College of Medicine, Konyang University) ;
  • Cho, Young Ho (Department of Pharmaceutics & Biotechnology, College of Medical Engineering, Konyang University) ;
  • Yoo, Yung Choon (Department of Microbiology, College of Medicine, Konyang University)
  • Received : 2018.01.04
  • Accepted : 2018.01.05
  • Published : 2018.03.28

Abstract

It is well known that Korean red ginseng has various biological activities. However, there is little knowledge about the antiviral activity of Korean red ginseng and its ginsenosides. In this study, we addressed whether oral administration of ginsenoside-Rb2 and -Rg3 is able to protect against rotavirus (RV) infection. The protective effect of ginsenosides against RV infection was examined using an in vivo experiment model in which newborn mice (10-day-old) were inoculated perorally (p.o.) with $1.5{\times}10^6$ plaque-forming units/mouse of RV strain SA11. When various dosages of ginsenoside-Rb2 (25-250 mg/kg) were administered 3days, 2 days, or 1 day before virus challenge, treatment with this ginsenoside at the dosage of 75 mg/kg 3days before virus infection most effectively reduced RV-induced diarrhea. In addition, consecutive administration of ginsenoside-Rb2 (75 mg/kg) at 3 days, 2 days, and 1 day before virus infection was more effective than single administration on day -3. The consecutive administration of ginsenoside-Rb2 also reduced virus titers in the bowels of RV-infected mice. In an experiment to compare the protective activity between ginsenoside-Rb2 and its two hydrolytic products (20(S)- and 20(R)-ginsenoside-Rg3), 20(S)-ginsenoside-Rg3, but not 20(R)-ginsenoside-Rg3, prevented RV infection. These results suggest that ginsenoside-Rb2 and its hydrolytic product, 20(S)-ginsenoside-Rg3, are promising candidates as an antiviral agent to protect against RV infection.

Keywords

References

  1. Desselberger U. 2014. Rotaviruses. Virus Res. 190: 75-96. https://doi.org/10.1016/j.virusres.2014.06.016
  2. Parashar UD, Burton A, Lanata C, Boschi-Pinto C, Shibuya K, Steele D, et al. 2009. Global mortality associated with rotavirus disease among children in 2004. J. Infect. Dis. 200: S9-S15. https://doi.org/10.1086/605025
  3. Jiang V, Jiang B, Tate J, Parashar UD, Patel MM. 2010. Performance of rotavirus vaccines in developed and developing countries. Hum. Vaccin. 6: 532-542. https://doi.org/10.4161/hv.6.7.11278
  4. Song X, Hu S. 2009. Adjuvant activities of saponins from traditional Chinese medicinal herbs. Vaccine 27: 4883-4890. https://doi.org/10.1016/j.vaccine.2009.06.033
  5. Sun HK, Xie Y, Ye YP. 2009. Advances in saponin-based adjuvants. Vaccine 13: 1787-1796.
  6. Kirk DD, Rempel R, Pinkhasov J, Walmsley AM. 2004. Application of Quillaja saponaria extracts as oral adjuvants for plant-made vaccines. Expert Opin. Biol. Ther. 4: 947-958. https://doi.org/10.1517/14712598.4.6.947
  7. Pickering RJ, Smith SD, Strugnell RA, Wesselingh SL, Webster DE. 2006. Crude saponins improve the immune response to an oral plant-made measles vaccine. Vaccine 24: 144-150. https://doi.org/10.1016/j.vaccine.2005.07.097
  8. Park D, Bae DK, Jeon JH, Lee N, Yang G, Yang YH, et al. 2011. Immunopotentiation and antitumor effects of a ginsenoside Rg-fortified red ginseng preparation in mice bearing H460 lung cancer cells. Environ. Toxicol. Pharmacol. 31: 397-405. https://doi.org/10.1016/j.etap.2011.01.008
  9. Yu JL, Dou DQ, Chen XH, Yang HZ, Guo N, Cheng GF. 2005. Protopanaxatriol-type ginsenosides differentially modulate type 1 and type 2 cytokines production from murine splenocytes. Planta Med. 71: 202-207. https://doi.org/10.1055/s-2005-837817
  10. Dong H, Bai LP, Wong VK, Zhou H, Wang JR, Liu Y, et al. 2011. The in vitro structure-related anti-cancer activity of ginsenosides and their derivatives. Molecules 9: 10619-10930.
  11. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono-oka S, et al. 1995. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol. Pharm. Bull. 18: 1197-1202.
  12. Musende AG, Eberding A, Wood CA, Adomat H, Fazli L, Hurtado-Coll A, et al. 2012. A novel oral dosage formulation of the ginsenoside aglycone protopanaxadiol exhibits therapeutic activity against a hormone-insensitive model of prostate cancer. Anticancer Drugs 23: 543-552. https://doi.org/10.1097/CAD.0b013e32835006f5
  13. Sato K, Mochizuki M, Saiki I, Yoo YC, Samukawa K, Azuma I. 1994. Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng, ginsenoside-Rb2. Biol. Pharm. Bull. 17: 635-639. https://doi.org/10.1248/bpb.17.635
  14. Cho JY, Kim AR, Yoo ES, Baik KU, Park MK. 2002. Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation. Planta Med. 68: 497-500. https://doi.org/10.1055/s-2002-32556
  15. Kim JY, Kim HJ, Kim HJ. 2011. Effect of oral administration of Korean red ginseng on influenza A (H1N1). J. Ginseng Res. 35: 104-110. https://doi.org/10.5142/jgr.2011.35.1.104
  16. Yoo DG, Kim MC, P ark MK, Song JM, Quan FS, P ark KM, et al. 2012. Protective effect of Korean red ginseng extract on the infections by H1N1 and H3N2 influenza viruses in mice. J. Med. Food 15: 855-862. https://doi.org/10.1089/jmf.2012.0017
  17. Lee MH, Lee BH, Jung JY, Cheon DS, Kim KT, Choi C. 2011. Antiviral effect of Korean red ginseng extract and ginsenosides on murine norovirus and feline calicivirus as surrogates for human norovirus. J. Ginseng Res. 35: 429-435. https://doi.org/10.5142/jgr.2011.35.4.429
  18. Lee KT, Jung TW, Lee HJ, Kim SG, Shin YS, Whang WK. 2011. The antidiabetic effect of ginsenoside Rb2 via activation of AMPK. Arch. Pharm. Res. 34: 1201-1208. https://doi.org/10.1007/s12272-011-0719-6
  19. Yoo YC, Lee J, Park SR, Nam KY, Cho YH, Choi JE. 2013. Protective effect of ginsenoside-Rb2 from Korean red ginseng on the lethal infection haemagglutinating virus of Japan in mice. J. Ginseng Res. 37: 80-86. https://doi.org/10.5142/jgr.2013.37.80
  20. Samukawa K, Yamashita H, Matsuda H, Kubo M. 1995. Simultaneous analysis of saponins in Ginseng Radix by high performance liquid chromatography. Chem. Pharm. Bull. 43: 437-141. https://doi.org/10.1248/cpb.43.137
  21. Fukushima A, Yoo YC, Yoshomatsu K, Matsuzawa K, Tamura M, Tono-oka S, et al. 1996. Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus. Vaccine 14: 485-491. https://doi.org/10.1016/0264-410X(95)00236-T
  22. Bomford R, Stapleton M, Winsor S, Beesley JE, Jessup EA, Price KR, et al. 1992. Adjuvanticity and ISCOM formation by structurally diverse saponins. Vaccine 10: 572-577.
  23. Yuki Y, Kiyono H. 2003. New generation of mucosal adjuvants for the induction of protective immunity. Rev. Med. Virol. 13: 293-310. https://doi.org/10.1002/rmv.398
  24. Sun Y, Guo M, Feng Y, Zheng H, Lei P, Ma X, et al. 2016. Effect of ginseng polysaccharides on NK cell cytotoxicity in immunosuppressed mice. Exp. Ther. Med. 12: 3773-3777 https://doi.org/10.3892/etm.2016.3840
  25. Du XF, Jiang CZ, Wu CF, Won EK, Choung SY. 2008. Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression. Arch. Pharm. Res. 31: 1153-1159. https://doi.org/10.1007/s12272-001-1282-6

Cited by

  1. Medicinal plants with anti-mutagenic potential vol.34, pp.1, 2020, https://doi.org/10.1080/13102818.2020.1749527
  2. 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
  3. Antiviral Effect of Ginsenoside Rb2 and Rb3 Against Bovine Viral Diarrhea Virus and Classical Swine Fever Virus in vitro vol.8, pp.None, 2018, https://doi.org/10.3389/fvets.2021.764909
  4. Bovine Lactoferricin Induces Intestinal Epithelial Cell Activation through Phosphorylation of FAK and Paxillin and Prevents Rotavirus Infection vol.31, pp.8, 2018, https://doi.org/10.4014/jmb.2106.06044
  5. MiRNA-221-5p suppressed the Th17/Treg ratio in asthma via RORγt/Foxp3 by targeting SOCS1 vol.17, pp.1, 2018, https://doi.org/10.1186/s13223-021-00620-8