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The Pharmaceutical Society of Korea (대한약학회)
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Transformation of Ginseng Saponins to Ginsenoside $Rh_2$ by Acids and Human Intestinal Bacteria Activities of Their Transformants

  • Published : 2004.01.01
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Abstract

When ginseng water extract was incubated at $60^{\circ}C$ in acidic conditions, its protopanaxadiol ginsenosides were transformed to ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$. However, protopanaxadiol glycoside ginsenosides $Rb_1, Rb_2$ and Rc isolated from ginseng were mostly not transformed to ginsenoside $Rg_3$ by the incubation in neutral condition. The transformation of these ginsenosides to ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$ was increased by increasing incubation temperature and time in acidic condition: the optimal incubation time and temperature for this transformation was 5 h and $60^{\circ}C$ resepectively. The transformed ginsenoside $Rg_3$ and ${\Delta}^{20}$-ginsenoside $Rg_3$ were metabolized to ginsenoside $Rh_2$ and $\Delta^{20}$--ginsenoside $Rh_2$, respectively, by human fecal microflora. Among the bacteria isolated from human fecal microflora, Bacteroides sp., and Bifidobacterium sp. and Fusobacterium sp. potently transformed ginsenoside $Rg_3$ to ginsenoside $Rh_2$. Acid-treated ginseng (AG) extract, fermented AG extract, ginsenoside $Rh_2$ and protopanaxadiol showed potent cytotoxicity against tumor cell lines. AG extract, fermented AG extract and protopanaxadiol potently inhibited the growth of Helicobacter pylori.

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References

  1. Akao, T., Kanaoka, M., and Kobashi, K., Appearance of compound K, a major metabolite of ginsenoside Rb, by intestinal bacteria, in rat plasma after oral administrationmeasurement of compound K by enzyme immunoassay. Biol. Pharm. Bull., 21, 245-249 (1998) https://doi.org/10.1248/bpb.21.245
  2. Akao, T., Kida, H., Kanaoka, M., Hattori, M., and Kobashi, K., Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside $Rb_1$ from Panax ginseng. J. Pharm. Pharmacol., 50, 1155-1160 (1998) https://doi.org/10.1111/j.2042-7158.1998.tb03327.x
  3. Bae, E.-A., Park, S.-Y., and Kim, D.-H., Constitutive $\beta$-glucosidases hydrolyzing ginsenoside $Rb_1$ and $Rb_2$ from human intestinal bacteria. Biol. Pharm. Bull., 23, 1481-1485 (2000) https://doi.org/10.1248/bpb.23.1481
  4. Bae, E. A., Han, M. J., Choo, M. K., Park, S. Y., and Kim, D. H., Metabolism of 20(S)- and 20(R)-ginsenoside $Rg_3$ by human intestinal bacteria and its relation to in vitro biological activities. Biol. Pharm. Bull., 25, 58-63 (2002) https://doi.org/10.1248/bpb.25.58
  5. Carmichael, J., DeGreff, W. G., Gazdar, A. F., Minna, J. D., and Mitchell, J. B., Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res., 47, 936-940(1987)
  6. Han, B. H., Park, M. H., Han, Y. N., Woo, L. K., Sankawa, U., Yahara, S., and Tanaka, O., Degradation of ginseng saponins under mild acidic conditions. Planta Med., 44, 146-149 (1982) https://doi.org/10.1055/s-2007-971425
  7. Hasegawa, H., Sung, J.-H., and Benno, Y., Role of human intestinal Prevotella oris in hydrolyzing Ginseng saponins. Planta Med., 63, 436-440 (1997) https://doi.org/10.1055/s-2006-957729
  8. Kanaoka, M, Kato, H. Shimada, F., and Yano, S., Studies on the enzyme immunoassay of bioactive constituents contained in oriental medicinal drugs. VI. Enzyme immunoassay of ginsenoside $Rb_1$ form Panax ginseng. Chem. Pharm. Bull., 40, 314-317 (1992) https://doi.org/10.1248/cpb.40.314
  9. Kanaoka, M., Akao, T., and Kobashi, K., Metabolism of ginseng saponins, ginsenosides, by human intestinal bacteria. J. Tradit. Med., 11, 241-245(1994)
  10. Karikura M., Miyaze T., Tanizawa H., Taniyzma T., and Takino Y., Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VII. Comparison of the decomposition modes of ginsenoside $Rb_1$ and $Rb_2$ in the digestive tract of rats. Chem. Pharm. Bull., 39, 2357-2361 (1991) https://doi.org/10.1248/cpb.39.2357
  11. Kitagawa, I., Yoshikawa, M., Yoshihara, M., Hayashi, T., and Taniyama, T., Chemical studies on crude drug precession. I. On the constituents of ginseng radix rubura (I). Yakugaku Zasshi, 103, 612-622 (1983) https://doi.org/10.1248/yakushi1947.103.6_612
  12. Kown, S. W., Han, S. B., Park, I. H., Kim, J. M., Park, M. K., and Park, J. H., Liquid chromatographic determination of less polar ginsenosides in processed ginseng. J. Chromatogr. A, 921, 335-339 (2001) https://doi.org/10.1016/S0021-9673(01)00869-X
  13. Lee, S. J., Sung, J. H., Lee, S. J., Moon, C. K., and Lee, B. H., Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin. Cancer Lett., 144, 39-43 (1999) https://doi.org/10.1016/S0304-3835(99)00188-3
  14. Mochizuki, M., Yoo, C. Y., Matsuzawa, K., Sato, K., Saiki, I., Tono-oka, S., Samukawa, K., and Azuma, I., Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside $Rb_2$, 20(R)- and 20(S)-ginsenoside $Rg_3$, of Red ginseng. Biol. Pharm. Bull., 18, 1197-1202 (1995) https://doi.org/10.1248/bpb.18.1197
  15. Sato, K., Mochizuki, M., Saiki, I., Yoo, Y. C., Samukawa K., and Azuma, I., Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng-ginsenoside $Rb_2$. Biol. Pharm. Bull., 17, 635-639 (1994) https://doi.org/10.1248/bpb.17.635
  16. Shibata, S., Fujita, M., Itokawa, H., Tanaka, O., and Ishii, T., Panaxadiol, a sapogenin of ginseng roots (1). Chem. Pharm. Bull., 11, 759-764 (1963) https://doi.org/10.1248/cpb.11.759
  17. Tanaka, N., Tanaka, O., and Shibata, S., Chemical studies on the oriental plant drugs. XXVIII. Saponins and sapogenins of ginseng; Stereochemistry of sapogenin of ginsenoside $Rb_1$, $Rb_2$ and Rc. Chem. Pharm. Bull., 20, 1212-1216 (1972) https://doi.org/10.1248/cpb.20.1212
  18. Wakabayashi, C., Hasegawa, H., Murata, J., and Saiki, I., In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol. Res., 9, 411-417 (1998)
  19. Wu, J. Y., Gardner, B. H., Murphy, C. I., Seals, J. R., Kensil, C. R., Recchia, J., Beltz, G. A., Newman, G. W., and Newman, M. J., Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. J. Immunol., 148, 1519-1525 (1992)