Archives of Pharmacal Research

, Volume 34, Issue 4, pp 681–685

Inhibitory effect of ginsenosides from steamed ginseng-leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells

  • Nguyen Huu Tung
  • Tran Hong Quang
  • Jeong-Hyun Son
  • Jung-Eun Koo
  • Hye-Jin Hong
  • Young-Sang Koh
  • Gyu Yong Song
  • Young Ho Kim
Research Articles Drug Actions

Abstract

Interleukin-12, a heterodimeric cytokine comprising p40 and p35 subunits, plays an essential role in the regulating the differentiation of Th cells, which establish and maximize the capabilities of the immune system. The aim of present study is to screen the effect of 21 ginsenosides from steamed ginseng-leaves and flowers on IL-12 production in bone marrow-derived dendritic cells induced by lipopolysaccharide. Noticeably, ginsenoside Rg6 (12) and ginsenoside F4 (13) exhibited particularly inhibitory effect on LPS-induced IL-12 production with the inhibition values of 80 and 82%; and ginsenoside ST1 (4), ginsenoside SL2 (8), ginsenoside SL3 (9), ginsenoside Rh3 (14), ginsenoside Rk2 (15), and ginsenoside Rs4 (18) showed moderate effects with inhibition rates of 63, 65, 67, 68, 71, 73, and 67%, respectively. These results warrant further studies concerning potential of saponin extracts of steamed ginseng-leaves and flowers for medicinal uses.

Key words

Interleukin 12 Panax ginseng Ginsenoside Bone marrow-derived dendritic cells 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe, H., Arichi, S., Hayashi, T., and Odashima, S., Ultrastructural studies of Morris hepatoma cells reversely transformed by ginsenosides. Experientia, 35, 1647–1649 (1979).PubMedCrossRefGoogle Scholar
  2. Akira, S. and Takeda, K., Toll-like receptor signalling. Nat. Rev. Immunol., 4, 499–511 (2004).PubMedCrossRefGoogle Scholar
  3. Choi, K., Kim, M., Ryu, J., and Choi, C., Ginsenosides compound K and Rh2 inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells. Neurosci. Lett., 421, 37–41 (2007).PubMedCrossRefGoogle Scholar
  4. Cooper, A. M. and Khader, S. A., IL-12p40: an inherently agonistic cytokine. Trends Immunol., 28, 33–38 (2007).PubMedCrossRefGoogle Scholar
  5. Gately, M. K., Renzetti, L. M., Magram, J., Stern, A. S., Adorini, L., Gubler, U., and Presky, D. H., The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. Annu. Rev. Immunol., 16, 495–521 (1998).PubMedCrossRefGoogle Scholar
  6. Mannon, P. J., Fuss, I. J., Mayer, L., Elson, C. O., Sandborn, W. J., Present, D., Dolin, B., Goodman, N., Groden, C., Hornung, R. L., Quezado, M., Yang, Z., Neurath, M. F., Salfeld, J., Veldman, G. M., Schwertschlag, U., and Strober, W., Anti-interleukin-12 antibody for active Crohn’s disease. N. Engl. J. Med., 351, 2069–2079 (2004).PubMedCrossRefGoogle Scholar
  7. Murphy, T. L., Cleveland, M. G., Kulesza, P., Magram, J., and Murphy, K. M., Regulation of interleukin 12 p40 expression through an NF-κB half-site. Mol. Cell. Biol., 15, 5258–5267 (1995).PubMedGoogle Scholar
  8. Park, J. D., Rhee, D. K., and Lee, Y. H., Biological activities and chemistry of saponins from Panax ginseng C. A. Meyer. Phytochem. Rev., 4, 159–175 (2005).CrossRefGoogle Scholar
  9. Plevy, S. E., Gemberling, J. H., Hsu, S., Dorner, A. J., and Smale, S. T., Multiple control elements mediate activation of the murine and human interleukin 12 p40 promoters: evidence of functional synergy between C/EBP and Rel proteins. Mol. Cell. Biol., 17, 4572–4588 (1997).PubMedGoogle Scholar
  10. Shibata, S., Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Korean Med. Sci., 16, S28–S37 (2001).PubMedGoogle Scholar
  11. Sugaya, A., Yuzurihara, M., Tsuda, T., Yasuda, K., Kajiwara, K., and Sugaya, E., Proliferative effect of ginseng saponin on neurite extension of primary cultured neurons of the rat cerebral cortex. J. Ethnopharmacol., 22, 173–181 (1988).PubMedCrossRefGoogle Scholar
  12. Taki, S., Sato, T., Ogasawara, K., Fukuda, T., Sato, M., Hida, S., Suzuki, G., Mitsuyama, M., Shin, E. H., Kojima, S., Taniguchi, T., and Asano, Y., Multistage regulation of Th1-type immune responses by the transcription factor IRF-1. Immunity, 6, 673–679 (1997).PubMedCrossRefGoogle Scholar
  13. Trinchieri, G., Pflanz, S., and Kastelein, R. A., The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses. Immunity, 19, 641–644 (2003).PubMedCrossRefGoogle Scholar
  14. Tung, N. H., Song, G. Y., Park, Y. J., and Kim, Y. H., Two new dammarane-type saponins from the leaves of Panax ginseng. Chem. Pharm. Bull., 57, 1412–1414 (2009).PubMedCrossRefGoogle Scholar
  15. Tung, N. H., Song, G. Y., Nhiem, N. X., Ding, Y., Tai, B. H., Jin, L. G., Lim, C. M., Hyun, J. W., Park, C. J., Kang, H. K., and Kim, Y. H., Dammarane-type saponins from the flower buds of Panax ginseng and their intracellular radical scavenging capacity. J. Agric. Food Chem., 58, 868–874 (2010a).PubMedCrossRefGoogle Scholar
  16. Tung, N. H., Cho, K., Kim, J. A., Song, G. Y., and Kim, Y. H., Dammarane-type glycosides from the steamed flowerbuds of Panax ginseng. Bull. Korean Chem. Soc., 31, 1381–1384 (2010b).CrossRefGoogle Scholar
  17. Tung, N. H., Song, G. Y., Kang, H.-K., and Kim, Y. H., New dammarane saponins from the steamed ginseng leaves. Bull. Korean Chem. Soc., 31, 2094–2096 (2010c).CrossRefGoogle Scholar
  18. Tung, N. H., Song, G. Y., Minh, C. V., Kiem, P. V., Jin, L. G., Boo, H.-J., Kang, H.-K., and Kim, Y. H., Steamed ginsengleaf components enhance cytotoxic effects on human leu kemia HL-60 cells. Chem. Pharm. Bull., 58, 1111–1115 (2010d).PubMedCrossRefGoogle Scholar
  19. Tung, N. H., Song, S. B., Song, G. Y., Kim, J.-A., Koo, J.-E., Kang, H.-K., Koh, Y.-S., and Kim, Y. H., Inhibitory effect of ginsenosides from ginseng leaves and flowers on the LPS-stimulated IL-12 production in bone marrow-derived dendritic cells. Food Sci. Biotechnol., 19, 1119–1122 (2010e).CrossRefGoogle Scholar
  20. Wolf, S. F., Temple, P. A., Kobayashi, M., Young, D., Dicig, M., Lowe, L., Dzialo, R., Fitz, L., Ferenz, C., Hewick, R. M., Kelleher, K., Herrmann, S. H., Clark, S. C., Azzoni, L., Cha, S. H., Trinchieri, G., and Perussia, B., Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J. Immunol., 146, 3074–3081 (1991).PubMedGoogle Scholar
  21. Wu, C. F., Bi, X. L., Yang, J. Y., Zhan, J. Y., Dong, Y. X., Wang, J. H., Wang, J. M., Zhang, R., and Li, X., Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. Int. Immunopharmacol., 7, 313–320 (2007).PubMedCrossRefGoogle Scholar
  22. Yokozawa, T., Oura, H., and Kawashima, Y., The effect of ginsenoside-Rb2 on nitrogen balance. J. Nat. Prod., 52, 1350–1352 (1989).PubMedCrossRefGoogle Scholar
  23. Yokozawa, T., Fujitsuka, N., Yasui, T., and Oura, H., Effects of ginsenoside-Rb2 on adenine nucleotide content of rat hepatic tissue. J. Pharm. Pharmacol., 43, 290–291 (1991).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2011

Authors and Affiliations

  • Nguyen Huu Tung
    • 1
  • Tran Hong Quang
    • 1
  • Jeong-Hyun Son
    • 1
  • Jung-Eun Koo
    • 2
  • Hye-Jin Hong
    • 2
  • Young-Sang Koh
    • 2
  • Gyu Yong Song
    • 1
  • Young Ho Kim
    • 1
  1. 1.College of PharmacyChungnam National UniversityDaejeonKorea
  2. 2.School of Medicine and Brain Korea 21 ProgramJeju National UniversityJejuKorea

Personalised recommendations