Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Inhibitory Effect of Ginsenoside-Rp1, a Novel Ginsenoside Derivative, on the Functional Activation of Macrophage-like Cells

  • Park, Tae-Yoon (CAmbo Institute) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University)
  • Published : 2008.12.31
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Abstract

Ginsenoside Rp1 (G-Rp1) is a ginseng saponin derivative with chemopreventive and anti-cancer activities. In this study, we examined the regulatory activity of G-Rp1 on the functional activation of macrophages. G-Rp1 remarkably inhibited TNF-$\alpha$ production, LPS-induced cell cytotoxicity, NO production, ROS generation, and phagocytic uptake from lipopolysacchride (LPS)-activated RAW264.7 cells. According to structural feature study using several G-Rp1 analogs, two carbohydrates (glucose-glucose) at R1 position were observedto be highly effective, compared to other structural derivatives. Although the inhibitory activities of G-Rp1 on macrophage functions were not remarkable, several points that G-Rp1 was known to be safe, and that this compound was orally effective, suggest that G-Rp1 may be beneficial in treating macrophage-mediated immunological diseases.

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References

  1. Bae, E. A., Kim, E. J., Park, J. S., Kim, H. S., Ryu, J. H., and Kim, D. H. (2006). Ginsenosides Rg3 and Rh2 inhibit the activation of AP-1 and protein kinase A pathway in lipopolysaccharide/interferon-gamma-stimulated BV-2 microglial cells. Planta Med. 72, 627-633 https://doi.org/10.1055/s-2006-931563
  2. Bai, X. C., Lu, D., Liu, A. L., Zhang, Z. M., Li, X. M., Zou, Z. P., Zeng, W. S., Cheng, B. L. and Luo, S. Q. (2005). Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast. J. Biol. Chem. 280, 17497-17506 https://doi.org/10.1074/jbc.M409332200
  3. Cho, J. Y., Baik, K. U., Jung, J. H. and Park, M. H. (2000). In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur. J. Pharmacol. 398, 399-407 https://doi.org/10.1016/S0014-2999(00)00337-X
  4. Cho, J. Y., Fox, D. A., Horejsi, V., Sagawa, K., Skubitz, K. M., Katz, D. R. and Chain, B. (2001a). The functional interactions between CD98, ${\beta}1$-integrins, and CD147 in the induction of U937 homotypic aggregation. Blood 98, 374-382 https://doi.org/10.1182/blood.V98.2.374
  5. Cho, J. Y., Yoo, E. S., Baik, K. U., Park, M. H. and Han, B. H. (2001b). In vitro inhibitory effect of protopanaxadiol ginsenosides on tumor necrosis factor (TNF)-alpha production and its modulation by known TNF-alpha antagonists. Planta. Med. 67, 213-218 https://doi.org/10.1055/s-2001-12005
  6. Choi, K., Kim, M., Ryu, J. and Choi, C. (2007). Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alphainduced activation of the NF-kappaB and JNK pathways in human astroglial cells. Neurosci. Lett. 421, 37-41 https://doi.org/10.1016/j.neulet.2007.05.017
  7. Choo, M. K., Sakurai, H., Kim, D. H. and Saiki, I. (2008). A ginseng saponin metabolite suppresses tumor necrosis factoralpha-promoted metastasis by suppressing nuclear factorkappaB signaling in murine colon cancer cells. Oncol. Rep. 19, 595-600
  8. Ding, M., Zhang, M., Wong, J. L., Rogers, N. E., Ignarro, L. J. and Voskuhl, R. R. (1998). Antisense knockdown of inducible nitric oxide synthase inhibits induction of experimental autoimmune encephalomyelitis in SJL/J mice. J. Immunol. 160, 2560-2564
  9. Gillis, C. N. (1997). Panax ginseng pharmacology: a nitric oxide link? Biochem. Pharmacol. 54, 1-8 https://doi.org/10.1016/S0006-2952(97)00193-7
  10. Gracie, J. A., Forsey, R. J., Chan, W. L., Gilmour, A., Leung, B. P., Greer, M. R., Kennedy, K., Carter, R., Wei, X. Q., Xu, D., Field, M., Foulis, A., Liew, F. Y. and McInnes, I. B. (1999). A proinflammatory role for IL-18 in rheumatoid arthritis. J. Clin. Invest. 104, 1393-1401 https://doi.org/10.1172/JCI7317
  11. Haberzettl, P., Duffin, R., Kramer, U., Hohr, D., Schins, R. P., Borm, P. J. and Albrecht, C. (2007). Actin plays a crucial role in the phagocytosis and biological response to respirable quartz particles in macrophages. Arch. Toxicol. 81, 459-470 https://doi.org/10.1007/s00204-007-0178-5
  12. Hong, S., Kim, S. H., Rhee, M. H., Kim, A. R., Jung, J. H., Chun, T., Yoo, E. S. and Cho, J. Y. (2003). In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges. Naunyn Schmiedebergs Arch. Pharmacol. 368, 448-456 https://doi.org/10.1007/s00210-003-0848-7
  13. Jung, C. H., Jun, C. Y., Lee, S., Park, C. H., Cho, K. and Ko, S. G. (2006). Rhus verniciflua stokes extract: radical scavenging activities and protective effects on H2O2-induced cytotoxicity in macrophage RAW 264.7 cell lines. Biol. Pharm. Bull. 29, 1603-1607 https://doi.org/10.1248/bpb.29.1603
  14. Kinne, R. W., Brauer, R., Stuhlmuller, B., Palombo-Kinne, E. and Burmester, G. R. (2000). Macrophages in rheumatoid arthritis. Arthritis Res. 2, 189-202 https://doi.org/10.1186/ar86
  15. Kumar, A., Kumar, M., Panwar, M., Samarth, R. M., Park, T. Y., Park, M. H. and Kimura, H. (2006). Evaluation of chemopreventive action of Ginsenoside Rp1. Biofactors 26, 29-43 https://doi.org/10.1002/biof.5520260104
  16. Lee, H. J., Hyun, E. A., Yoon, W. J., Kim, B. H., Rhee, M. H., Kang, H. K., Cho, J. Y. and Yoo, E. S. (2006), In vitro antiinflammatory and anti-oxidative effects of Cinnamomum camphora extracts. J. Ethnopharmacol. 103, 208-216 https://doi.org/10.1016/j.jep.2005.08.009
  17. Lee, J. Y., Rhee, M. H. and Cho, J. Y. (2008a). Novel modulatory effects of SDZ 62-434 on inflammatory events in activated macrophage-like and monocytic cells. Naunyn Schmiedebergs Arch. Pharmacol. 377, 111-124 https://doi.org/10.1007/s00210-008-0266-y
  18. Lee, Y. G., Kim, J. Y., Lee, J. Y., Byeon, S. E., Hong, E. K., Lee, J., Rhee, M. H., Park, H. J. and Cho, J. Y. (2007). Regulatory effects of Codonopsis lanceolata on macrophage-mediated immune responses. J. Ethnopharmacol. 112, 180-188 https://doi.org/10.1016/j.jep.2007.02.026
  19. Lee, Y. G., Lee, W. M., Kim, J. Y., Lee, J. Y., Lee, I. K., Yun, B. S., Rhee, M. H. and Cho, J. Y. (2008b). Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7 cells. Br. J. Pharmacol. 154, 852-863 https://doi.org/10.1038/bjp.2008.136
  20. Michaelsson, E., Holmdahl, M., Engstrom, A., Burkhardt, H., Scheynius, A. and Holmdahl, R. (1995). Macrophages, but not dendritic cells, present collagen to T cells. Eur. J. Immunol. 25, 2234-2241 https://doi.org/10.1002/eji.1830250818
  21. Miller, Y. I., Worrall, D. S., Funk, C. D., Feramisco, J. R. and Witztum, J. L. (2003). Actin polymerization in macrophages in response to oxidized LDL and apoptotic cells: role of 12/15-lipoxygenase and phosphoinositide 3-kinase. Mol. Biol. Cell. 14, 4196-4206 https://doi.org/10.1091/mbc.E03-02-0063
  22. Park M. H. and Park T. Y. (2005). Novel ginsenoside preparation with anti-cancer activity. PCT/KR2005/117501
  23. Plenz, G. and Robenek, H. (1998). Monocytes/macrophages in atherosclerosis. Eur. Cytokine. Netw. 9, 701-703
  24. Shin, Y. W., Bae, E. A., Kim, S. S., Lee, Y. C., Lee, B. Y., and Kim, D. H. (2006). The effects of ginsenoside Re and its metabolite, ginsenoside Rh1, on 12-O-tetradecanoylphorbol 13-acetate- and oxazolone-induced mouse dermatitis models. Planta Med. 72, 376-378 https://doi.org/10.1055/s-2005-916217
  25. Vandana, S., Ram, S., Ilavazhagan, M., Kumar, G. D. and Banerjee, P. K. (2006). Comparative cytoprotective activity of vitamin C, E and beta-carotene against chromium induced oxidative stress in murine macrophages. Biomed. Pharmacother. 60, 71-76 https://doi.org/10.1016/j.biopha.2005.04.005
  26. Wang, E., Michl, J., Pfeffer, L. M., Silverstein, S. C. and Tamm, I. (1984). Interferon suppresses pinocytosis but stimulates phagocytosis in mouse peritoneal macrophages: related changes in cytoskeletal organization. J. Cell. Biol. 98, 1328-1341 https://doi.org/10.1083/jcb.98.4.1328

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