Effects of Ginsenosides Rd and Rg1 on Proliferation of B Cells and Antibody Induction

Rd와 Rg1 인삼배당체의 B 임파구 증식 및 항체 유도 효과

  • Joo, Inkyung (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University) ;
  • Kim, Hayan (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University) ;
  • Kim, Jeonghyeon (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University) ;
  • Shehzad, Omer (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Kim, Yeong Shik (Natural Products Research Institute, College of Pharmacy, Seoul National University) ;
  • Han, Yongmoon (Department of ImmunoMicrobiology, College of Pharmacy, Dongduk Women's University)
  • 주인경 (동덕여자대학교 약학대학 면역.미생물학교실) ;
  • 김하얀 (동덕여자대학교 약학대학 면역.미생물학교실) ;
  • 김정현 (동덕여자대학교 약학대학 면역.미생물학교실) ;
  • 쉐자드 오마 (서울대학교 약학대학 천연물연구소) ;
  • 김영식 (서울대학교 약학대학 천연물연구소) ;
  • 한용문 (동덕여자대학교 약학대학 면역.미생물학교실)
  • Received : 2012.12.26
  • Accepted : 2013.02.05
  • Published : 2013.02.28

Abstract

Induction of effective and increased levels of antibody production may be major points in vaccine development. This is especially the case when the antigenic sources are carbohydrates. Thus, in our Lab various types of formulations such as liposomal and conjugate vaccines have been researched. However, the fastidious formulation process and high costs are a problem. For this reason, there is currently a focus on utilizing immunoadjuvants. In this present study, we tested whether ginsenosides Re (a panaxdiol) and Rg1 (a panaxtriol) from Panax ginseng have immunoadjuvant activity against the cell wall of Candida albicans (CACW). The resulting data showed that Rd and Rg1 caused LPS-treated B lymphocytes to be proliferative. Rd had greater proliferation activity than that of Rg1. In the murine model of antibody production, CACW combined with Rd [CACW/Rd/IFA] or Rg1 [CACW/Rg1/IFA] increased the production of antibodies specific to C. albicans when compared to the antibody production by [CACW/IFA]-induction, which was used as a negative control (P<0.05). In the case of [CFA/Rd/IFA], the antibody production was almost twice as that of the CFA. In addition, formulations containing either had a prolonged antibody inducing activity as compared to the CFA formula. In conclusion, Rd and Rg1 have an immunologic activity, and yet Rd can be a better candidate than Rg1 for a new immunoadjuvant.

Acknowledgement

Supported by : 한국연구재단

References

  1. Ronin, C. : Remodeling of glycoprotein and carbohydrate antigens. Clin. Chem. Lab. Med. 36, 373 (1998).
  2. Ravdin, J. I., Shain, D. C. and Kelsall, B. L. : Antigenicity, immunogenicity and vaccine efficacy of the galactose-specific adherence protein of Entamoeba histolytica. Vaccine 11, 241 (1993). https://doi.org/10.1016/0264-410X(93)90024-R
  3. Han, Y. and Cutler, J. E. : Antibody response that protects against disseminated candidiasis. Infect. Immun. 63, 2714 (1995).
  4. Han, Y., Ulrich, M. A. and Cutler, J. E. : Candida albicans mannan extract-protein conjugates induce a protective immune response against experimental candidiasis. J. Infect. Dis. 179, 1477 (1999). https://doi.org/10.1086/314779
  5. Schijns, V. E. and Lavelle, E. C. : Trends in vaccine adjuvants. Expert. Rev. Vaccines 10, 539 (2011). https://doi.org/10.1586/erv.11.21
  6. O'Hagan, D. T., Ott, G. S., De Gregorio, E. and Seubert, A. : The mechanism of action of MF59 - an innately attractive adjuvant formulation. Vaccine 30, 4341 (2012). https://doi.org/10.1016/j.vaccine.2011.09.061
  7. Ferko, B., Kittel, C., Romanova, J., Sereinig, S., Katinger, H. and Egorov, A. : Live attenuated influenza virus expressing human interleukin-2 reveals increased immunogenic potential in young and aged hosts. J. Virol. 80, 11621 (2006). https://doi.org/10.1128/JVI.01645-06
  8. Gillis, CN. : Panax ginseng pharmacology: A nitric oxide link? Biochem. Pharmacol. 54, 1 (1997). https://doi.org/10.1016/S0006-2952(97)00193-7
  9. Sonnenborn, U. and Proppert, Y. : Ginseng (Panax ginseng C. A. Meyer). Br. J. Phytother. 2, 3 (1991).
  10. Kitagawa, I., Taniyama, T., Hayashi, T. and Yoshikawa, M. : Malonylginsenoside Rb1, Rb2, Rc and Rd, four new malonylated dammarane type triterpene oligosaccharides from Ginseng Radix. Chem. Pharm. Bull. 31, 3353 (1983). https://doi.org/10.1248/cpb.31.3353
  11. Shibata, S. : Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Korean Med. Sci. Suppl, S28 (2001).
  12. Zhang, G. Z., Liu, A. L., Zhou, Y. B., San, X., Jin, T. W. and Jin, Y. : Panax ginseng ginsenoside-Rg(2) protects memory impairment via anti-apoptosis in a rat model with vascular dementia. J. Ethnopharm. 115, 441 (2008). https://doi.org/10.1016/j.jep.2007.10.026
  13. Xu, L., Chen, W. F. and Wong M. S. : Ginsenoside Rg1 protects dopaminergic neurons in a rat model of Parkinson's disease through the IGF-I receptor signalling pathway. Br. J. Pharmacol. 158, 738 (2009). https://doi.org/10.1111/j.1476-5381.2009.00361.x
  14. Wang, C. Z., Mehendale, S. R. and Yuan, C. S. : Commonly used antioxidant botanicals: active constituents and their potential role in cardiovascular illness. Am. J. Chin. Med. 35, 543 (2007). https://doi.org/10.1142/S0192415X07005053
  15. Zhang, D., Yasuda, T., Yu, Y., Zheng, P., Kawabata, T., Ma, Y. and Okada, S. : Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation. Free Radical Biol. Med. 20, 145 (1996). https://doi.org/10.1016/0891-5849(95)02020-9
  16. Kuo, S. C., Teng, C. M., Lee, J. C., Ko, F. N., Chen, S. C. and Wu, T. S. : Antiplatelet components in Panax ginseng. Planta. Med. 56, 164 (1990). https://doi.org/10.1055/s-2006-960916
  17. Attele, A. S., Zhou, Y. P., Xie, J. T., Wu, J. A., Zhang, L., Dey, L., Pugh, W., Rue, P. A., Polonsky, K. S. and Yuan, C. S. : Antidiabetic effects of Panax ginseng berry extract and the identification of an effective component. Diabetes 51, 1851 (2002). https://doi.org/10.2337/diabetes.51.6.1851
  18. Li, W., Zhang, M., Gu, J., Meng, Z. J., Zhao, L. C., Zheng, Y. N., Chen, L. and Yang, G. L. : Hypoglycemic effect of protopanaxadiol-type ginsenosides and compound K on Type 2 diabetes mice induced by high-fat diet combining with streptozotocin via suppression of hepatic gluconeogenesis. Fitoterapia 83, 192 (2012). https://doi.org/10.1016/j.fitote.2011.10.011
  19. Ota, T., Fujikawa-Yamamoto, K., Zong, Z. P., Yamazaki, M., Odashima, S., Kitagawa, I., Abe, H. and Arichi S. : Plantglycoside modulation of cell surface related to control of differentiation in cultured B16 melanoma cells. Cancer Res. 47, 3863 (1987).
  20. Qi, L. W., Wang, C. Z. and Yuan, C. S. : Ginsenosides from American ginseng: chemical and pharmacological diversity. Phytochemistry 72, 689 (2011). https://doi.org/10.1016/j.phytochem.2011.02.012
  21. Zhu, J. H., Takeshita, T., Kitagawa, I. and Morimoto, K. : Suppression of the formation of sister chromatid exchanges by low concentrations of ginsenoside Rh2 in human blood lymphocytes. Cancer Res. 55, 1221 (1995).
  22. Saito, H., Tsuchiya, M., Naka, S. and Takagi, K. : Effect of Panax ginseng root on conditioned avoidance response in rats. Jpn. J. Pharmacol. 27, 509 (1977). https://doi.org/10.1254/jjp.27.509
  23. Tadano, T., Nakagawasai, O., Niijima, F., Tan-No, K. and Kisara, K. : The effects of traditional tonics on fatigue in mice differ from those of the antidepressant imipramine: a pharmacological and behavioral study. Am. J. Chin. Med. 28, 97 (2000). https://doi.org/10.1142/S0192415X0000012X
  24. Wang, L. C. and Lee, T. F. : Effects of ginseng saponins on cold tolerance in young and elderly rats. Planta. Med. 66, 144 (2000). https://doi.org/10.1055/s-2000-11122
  25. Sugiyama, K., Ueda, H., Shara, Y., Kajima, Y., Ichio, Y. and Yokota, M. : Protective effect of sodium l-malate, an active constituent isolated from Angelicae Radix, on cisdiamminedichloroplatinum( II)-induced toxic side effect. Chem. Pharm. Bull. 42, 2565 (1994). https://doi.org/10.1248/cpb.42.2565
  26. Hiai, S., Sasaki, S. and Oura, H. : Effect of ginseng saponin on rat adrenal cyclic AMP. Planta. Med. 37, 15 (1979). https://doi.org/10.1055/s-0028-1097289
  27. Kim, J. Y., Germolec, D. R. and Luster, M. I. : Panax ginseng as a potential immunomodulator: Studies in mice. Immunopharmacol Immunotoxicol. 12, 257 (1990). https://doi.org/10.3109/08923979009019672
  28. Han, Y., Kanbe, T. K., Cherniak, R. and Cutler, J. E. : Biochemical characterization of Candida albicans epitops that can elicit protective and nonprotective antibodies. Infect. Immun. 65, 4100 (1997).
  29. Han, Y., Kozel, T. R., Zhang, M. X., MacGill, R. S., Carroll, M. C. and Cutler J. E. : Complement is essential for protection by an IgM and an IgG3 monoclonal antibody against experimental, hematogenously disseminated candidiasis. J. Immunol. 167, 1550 (2001). https://doi.org/10.4049/jimmunol.167.3.1550
  30. Han, Y., Morrison, R. P. and Cutler, J. E. : A vaccine and monoclonal antibodies that enhance mouse resistance to Candida albicans vaginal infection. Infect. Immun. 66, 5771 (1998).
  31. Shezard, O., Ha, I. J., Park, Y., Ha, Y. W. and Kim, Y. S. : Development of a rapid and convenient method to separate eight ginsenosides from Panax ginseng by high-speed countercurrent chromatography coupled with evaporatative light scattering detection. J. Separation Sci. 34, 1116 (2011). https://doi.org/10.1002/jssc.201000932
  32. Rhew, K. Y. and Han, Y. : Immunoadjuvant activity of icariin that induces Th1-type antibody in mice. Arc. Pharm. Res. 35, 1685 (2012). https://doi.org/10.1007/s12272-012-0920-2
  33. Kim, J. Han, B. J., Kim, H., Lee, J. Y., Joo, I., Omer, S., Kim, Y. S. and Han, Y. : Th1 immunity induction by ginsenoside Re involves in protection of mice against disseminated candidiasis due to Candida albicans. Int. Immunopharm. 14, 481 (2012). https://doi.org/10.1016/j.intimp.2012.08.014
  34. Lee, J. H., Lee, J. Y., Park, J. H., Jung, H. S., Kim, J. S., Kang, S. S., Kim, Y. S. and Han, Y. : Immunoregulatory activity by daucosterol, a ß-sitosterol glycoside, induces protective Th1 immune respinse against disseminated Candidiasis in mice. Vaccine 25, 3834 (2007). https://doi.org/10.1016/j.vaccine.2007.01.108
  35. Lee, J. H. and Han, Y. : Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4+ T cell. Int. Immunopharm. 6, 1424 (2006). https://doi.org/10.1016/j.intimp.2006.04.009
  36. Demetrius, J. : Aging in mouse and human systems: A comparative study. Ann. N.Y. Acad. Sci. 1067, 66 (2006). https://doi.org/10.1196/annals.1354.010