Food Science and Biotechnology

, Volume 28, Issue 1, pp 237–242 | Cite as

Ginsenosides from Korean red ginseng modulate T cell function via the regulation of NF-AT-mediated IL-2 production

  • Le Ba Vinh
  • Jung Up Park
  • Le Xuan Duy
  • Nguyen Thi Minh Nguyet
  • Seo Young Yang
  • Young Ran Kim
  • Young Ho KimEmail author


Korean red ginseng is a traditional health food frequently used to prevent or treat various diseases worldwide. In this study, we evaluated the immunomodulatory activities of eleven compounds (1–11) isolated from Korean red ginseng, focusing on T cell function. First, the effects of the eleven compounds were studied on the regulation of IL-2, a potent T cell growth factor. Compounds 5, 7, and 9 significantly increased IL-2 secretion in phorbol 12-myristate 13-acetate (PMA)/ionomycin (Io)-induced EL-4 T cells. Next, we examined the effects of compounds 5, 7, and 9 on the regulation of transcription factors related to IL-2 production in T cells. Compound 9 significantly increased the PMA/Io-induced promoter activity of nuclear factor of activated T cells (NF-AT) in EL-4 T cells, but did not have any significant effects on the promoters of NF- κB. These results suggest that compound 9 activates T cell function via the regulation of NF-AT-mediated IL-2 production.


Panax ginseng Korean red ginseng Ginsenosides IL-2 



This research was financially supported by the Priority Research Center Program (Code: 2009-0093815) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology Korea.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

10068_2018_428_MOESM1_ESM.pdf (95 kb)
Supplementary material 1 (PDF 94 kb)


  1. Atopkina LN, Malinovskaya GV, Elyakov GB, Uvarova NI, Woerdenbag HJ, Koulman A, Pras N, Potier P. Cytotoxicity of natural ginseng glycosides and semisynthetic analogues. Planta Med. 65:30–34 (1999)CrossRefGoogle Scholar
  2. Attele AS, Wu JA, Yuan C-S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol. 58:1685–1693 (1999)CrossRefGoogle Scholar
  3. Chen F, Sun Y, Zheng SL, Qin Y, McClements DJ, Hu JN, Deng ZY. Antitumor and immunomodulatory effects of ginsenoside Rh2 and its octyl ester derivative in H22 tumor-bearing mice. J. Funct. Foods 32:382–390 (2017)CrossRefGoogle Scholar
  4. Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine. 28:109–123 (2004)CrossRefGoogle Scholar
  5. He LX, Ren JW, Liu R, Chen QH, Zhao J, Wu X, Zhang ZF, Wang JB, Pettinato G, Li Y. Ginseng (Panax ginseng Meyer) oligopeptides regulate innate and adaptive immune responses in mice via increased macrophage phagocytosis capacity, NK cell activity and Th cells secretion. Food Funct. 8:3523–3532 (2017)CrossRefGoogle Scholar
  6. Jia L, Zhao Y, Liang XJ. Current evaluation of the millennium phytomedicine-ginseng (II): Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine. Curr. Med. Chem. 16:2924–2942 (2009)CrossRefGoogle Scholar
  7. Jiang Z, Yang Y, Yang Y, Zhang Y, Yue Z, Pan Z, Ren X. Ginsenoside Rg3 attenuates cisplatin resistance in lung cancer by downregulating PD-L1 and resuming immune. Biomed. Pharmacother. 96:378-383 (2017)CrossRefGoogle Scholar
  8. Kang S, Min H. Ginseng, the’immunity boost’: the effects of Panax ginseng on immune system. J. Ginseng Res. 36:354 (2012)CrossRefGoogle Scholar
  9. Kara EE, Comerford I, Fenix KA, Bastow CR, Gregor CE, McKenzie DR, McColl SR. Tailored immune responses: novel effector helper T cell subsets in protective immunity. PLoS Pathog. 10:e1003905 (2014)CrossRefGoogle Scholar
  10. Kim HP, Imbert J, Leonard WJ. Both integrated and differential regulation of components of the IL-2/IL-2 receptor system. Cytokine Growth Factor 17:349–366 (2006)CrossRefGoogle Scholar
  11. Lee J-H, Han Y. Ginsenoside Rg1 helps mice resist to disseminated candidiasis by Th1 type differentiation of CD4 + T cell. Int. Immunopharmacol 6:1424–1430 (2006)CrossRefGoogle Scholar
  12. Liu JO. Calmodulin‐dependent phosphatase, kinases, and transcriptional corepressors involved in T‐cell activation. Immunol. Rev. 228:184–198 (2009)CrossRefGoogle Scholar
  13. Macian F. NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5:472–484 (2005)CrossRefGoogle Scholar
  14. Maloy KJ, Powrie F, Regulatory T cells in the control of immune pathology. Nat. Immunol. 2:816–822 (2001)CrossRefGoogle Scholar
  15. Park JU, Kang BY, Lee HJ, Kim S, Bae D, Park JH, Kim YR Tetradecanol reduces EL-4 T cell growth by the down regulation of NF-κB mediated IL-2 secretion. Eur. J. Pharmacol. 799:135–142 (2017a)CrossRefGoogle Scholar
  16. Park JU, Kang BY, Lee HJ, Kim S, Bae D, Park JH, Kim YR. Tetradecanol reduces EL-4 T cell growth by the down regulation of NF-κB mediated IL-2 secretion. Eur. J. Pharmacol. 799:135–142 (2017b)CrossRefGoogle Scholar
  17. Read KA, Powell MD, McDonald PW, Oestreich KJ. IL-2, IL-7, and IL-15: Multistage regulators of CD4 + T helper cell differentiation. Exp. Hematol. 44:799–808 (2016)Google Scholar
  18. Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by γc family cytokines. Nat Rev Immunol 9:480-490CrossRefGoogle Scholar
  19. Sarikahya NB, Nalbantsoy A, Top H, Gokturk RS, Sumbul H, Kirmizigul S. Immunomodulatory, hemolytic and cytotoxic activity potentials of triterpenoid saponins from eight Cephalaria species. Phytomedicine 38:135–144 (2018)CrossRefGoogle Scholar
  20. Shi Q, Shi X, Zuo G, Xiong W, Li H, Guo P, Wang F, Chen Y, Li J, Chen DL. Anticancer effect of 20 (S)-ginsenoside Rh2 on HepG2 liver carcinoma cells: Activating GSK-3β and degrading β-catenin. Oncol. Rep. 36:2059–2070 (2016)CrossRefGoogle Scholar
  21. Sim GC, Martin-Orozco N, Jin L, Yang Y, Wu S, Washington E, Sanders D, Lacey C, Wang Y, Vence L. IL-2 therapy promotes suppressive ICOS + Treg expansion in melanoma patients. J. Clin. Investig. 124:99–110 (2014)CrossRefGoogle Scholar
  22. Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 25:377–390 (2014)CrossRefGoogle Scholar
  23. Smith KA. Interleukin-2. Curr. Opin. Immunol. 4:271–276 (1992)CrossRefGoogle Scholar
  24. Vinh LB, Lee Y, Han YK, Kang JS, Park JU, Kim YR, Yang SY, Kim YH Two new dammarane-type triterpene saponins from Korean red ginseng and their anti-inflammatory effects. Bioorg. Med. Chem. Lett. 27:5149–5153 (2017)Google Scholar
  25. Wang C, He H, Dou G, Li J, Zhang X, Jiang M, Li P, Huang X, Chen H, Li L. Ginsenoside 20 (S)-Rh2 induces apoptosis and differentiation of acute myeloid leukemia cells: role of orphan nuclear receptor Nur77. J. Agric. Food Chem. 65:7687–7697 (2017)CrossRefGoogle Scholar
  26. Williams MA, Tyznik AJ, Bevan MJ. Interleukin-2 signals during priming are required for secondary expansion of CD8 + memory T cells. Nature 441:890 (2006)CrossRefGoogle Scholar
  27. Yang Z, Chen A, Sun H, Ye Y, Fang W Ginsenoside Rd elicits Th1 and Th2 immune responses to ovalbumin in mice. Vaccine 25:161–169 (2007)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Le Ba Vinh
    • 1
    • 2
  • Jung Up Park
    • 3
  • Le Xuan Duy
    • 1
    • 4
  • Nguyen Thi Minh Nguyet
    • 1
  • Seo Young Yang
    • 1
  • Young Ran Kim
    • 3
  • Young Ho Kim
    • 1
    Email author
  1. 1.College of PharmacyChungnam National UniversityDaejeonRepublic of Korea
  2. 2.Institute of Marine Biochemistry (IMBC)Vietnam Academy of Science and Technology (VAST)HanoiVietnam
  3. 3.College of Pharmacy and Research Institute of Drug DevelopmentChonnam National UniversityGwangjuRepublic of Korea
  4. 4.Institute of Natural Products ChemistryVietnam Academy of Science and Technology (VAST)HanoiVietnam

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