Skip to main content
SpringerLink
Log in

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

  • Published:
Food Science and Biotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • 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)

    Article  CAS  Google Scholar 

  • Attele AS, Wu JA, Yuan C-S. Ginseng pharmacology: multiple constituents and multiple actions. Biochem. Pharmacol. 58:1685–1693 (1999)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • Gaffen SL, Liu KD. Overview of interleukin-2 function, production and clinical applications. Cytokine. 28:109–123 (2004)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • Kang S, Min H. Ginseng, the’immunity boost’: the effects of Panax ginseng on immune system. J. Ginseng Res. 36:354 (2012)

    Article  CAS  Google Scholar 

  • 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)

    Article  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • Liu JO. Calmodulin‐dependent phosphatase, kinases, and transcriptional corepressors involved in T‐cell activation. Immunol. Rev. 228:184–198 (2009)

    Article  CAS  Google Scholar 

  • Macian F. NFAT proteins: key regulators of T-cell development and function. Nat. Rev. Immunol. 5:472–484 (2005)

    Article  CAS  Google Scholar 

  • Maloy KJ, Powrie F, Regulatory T cells in the control of immune pathology. Nat. Immunol. 2:816–822 (2001)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • Rochman Y, Spolski R, Leonard WJ. New insights into the regulation of T cells by γc family cytokines. Nat Rev Immunol 9:480-490

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • Sim GC, Radvanyi L. The IL-2 cytokine family in cancer immunotherapy. Cytokine Growth Factor Rev. 25:377–390 (2014)

    Article  CAS  Google Scholar 

  • Smith KA. Interleukin-2. Curr. Opin. Immunol. 4:271–276 (1992)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

  • 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)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea

    Le Ba Vinh, Le Xuan Duy, Nguyen Thi Minh Nguyet, Seo Young Yang & Young Ho Kim

  2. Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam

    Le Ba Vinh

  3. College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Gwangju, 500-757, Republic of Korea

    Jung Up Park & Young Ran Kim

  4. Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology (VAST), 18 Hoang Quoc Viet, Caugiay, Hanoi, Vietnam

    Le Xuan Duy

Authors
  1. Le Ba Vinh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jung Up Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Le Xuan Duy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nguyen Thi Minh Nguyet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seo Young Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Young Ran Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Young Ho Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Young Ho Kim.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 94 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vinh, L.B., Park, J.U., Duy, L.X. et al. Ginsenosides from Korean red ginseng modulate T cell function via the regulation of NF-AT-mediated IL-2 production. Food Sci Biotechnol 28, 237–242 (2019). https://doi.org/10.1007/s10068-018-0428-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10068-018-0428-8

Keywords

Search

Navigation