DOI QR코드

DOI QR Code

Bioavailability of Fermented Korean Red Ginseng

  • Published : 2009.09.30

Abstract

In an effort to improve ginsenoside bioavailability, the ginsenosides of fermented red ginseng were examined with respect to bioavailability and physiological activity. The results showed that the fermented red ginseng (FRG) had a high level of ginsenoside metabolites. The total ginsenoside contents in non-fermented red ginseng (NFRG) and FRG were 35715.2 ${\mu}g$/mL and 34822.9 ${\mu}g$/mL, respectively. However, RFG had a higher content (14914.3 ${\mu}g$/mL) of ginsenoside metabolites (Rg3, Rg5, Rk1, CK, Rh1, F2, and Rg2) compared to NFRG (5697.9 ${\mu}g$/mL). The skin permeability of RFG was higher than that of NFRG using Franz diffusion cells. Particularly, after 5 hr, the skin permeability of RFG was significantly (p<0.05) higher than that of NFRG. Using everted instestinal sacs of rats, RFG showed a high transport level (10.3 mg of polyphenols/g sac) compared to NFRG (6.67 of mg of polyphenols/g sac) after 1 hr. After oral administration of NFRG and FRG to rats, serum concentrations were determined by HPLC. Peak concentrations of Rk1, Rh1, Rc, and Rg5 were approximately 1.64, 2.35, 1.13, and 1.25-fold higher, respectively, for FRG than for NFRG. Furthermore, Rk1, Rh1, and Rg5 increased more rapidly in the blood by the oral administration of FRG versus NFRG. FRG had dramatically improved bioavailability compared to NFRG as indicated by skin permeation, intestinal permeability, and ginsenoside levels in the blood. The significantly greater bioavailability of FRG may have been due to the transformation of its ginsenosides by fermentation to more easily absorbable forms (ginsenoside metabolites).

References

  1. Park JH. 2004. Sun ginseng-a new processed ginseng with fortified activity. Food Ind Nutr 9: 23-27
  2. Kitagawa I, Yoshikawa M, Yoshihara M, Hayashi T, Taniyama T. 1983. Chemical studies of crude drugs (1). Constituents of Ginseng radix rubra. Yakugaku Zasshi 103: 612-622 https://doi.org/10.1248/yakushi1947.103.6_612
  3. Wu JY, Gardner BH, Murphy CI, Seals JR, Kensil CR, Recchia J, Beltz GA, Newman GW, Newman MJ. 1992. Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. J Immunol 148: 1519-1525
  4. Mochizuki M, Yoo CY, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I. 1995. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside Rb2, 20(R)- and 20(S)-ginsenoside Rg3, of red ginseng. Biol Pharm Bull 18: 1197-1202 https://doi.org/10.1248/bpb.18.1197
  5. Sato K, Mochizuki M, Saiki I, Yoo YC, Samukawa K, Azuma I. 1994. Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng-ginsenoside Rb2. Biol Pharm Bull 17: 635-639 https://doi.org/10.1248/bpb.17.635
  6. Bae EA, Park SY, Kim DH. 2000. Constitutive $\beta$-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 23: 1481-1485 https://doi.org/10.1248/bpb.23.1481
  7. Bae EA, Han MJ, Choo MK, Park SY, Kim DH. 2002. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 25: 58-63 https://doi.org/10.1248/bpb.25.58
  8. Kanaoka M, Akao T, Kobashi K. 1994. Metabolism of ginseng saponins, ginsenosides, by human intestinal bacteria. J Tradit Med 11: 241-245
  9. Wakabayashi C, Hasegawa H, Murata J, Saiki I. 1997. In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol Res 9: 411-417
  10. Wakabayashi C, Hasegawa H, Murata J, Saiki I. 1997. The expression of in vivo anti-metastatic effect of ginseng protopanaxatriol saponins is mediated by their intestinal bacterial metabolites after oral administration. J Trad Med 14: 180-185
  11. Hasegawa H, Lee KS, Nagaoka T, Tezuka Y, Uchiyama M, Kadota S, Saiki I. 2000. Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters. Biol Pharm Bull 23: 298-304 https://doi.org/10.1248/bpb.23.298
  12. Hasegawa H, Saiki I. 2000. Oleoyl triterpene glycoside biosynthesized from ginseng suppresses growth and metastasis of murine melanoma B16-F10 tumor via immunostimulation. J Trad Med 17: 186-193
  13. Hasegawa H, Suzuki R, Nagaoka T, Tezuka Y, Kadota S, Saiki I. 2000. Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acidconjugate of protopanaxatriol. Biol Pharm Bull 25: 861-866 https://doi.org/10.1248/bpb.25.861
  14. Hur HJ, Lee KW, Kim HY, Chung DK, Lee HJ. 2006. In vitro immunopotentiating activities of cellular fractions of lactic acid bacteria isolated from kimchi and bifidobacteria. J Microbiol Biotechnol 16: 661-666
  15. Wakabayashi C, Murakami K, Hasegawa H, Murata J, Saiki I. 1998. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 246: 725-730 https://doi.org/10.1006/bbrc.1998.8690
  16. Lou DW, Saito Y, Jinno K. 2005. Solid-phase extraction and high-performance liquid chromatography for simultaneous determination of important bioactive ginsenosides in pharmaceutical preparations. Chromatographia 62: 349-354 https://doi.org/10.1365/s10337-005-0640-6
  17. Kim SJ, Murthy HN, Hahna EJ, Lee HL, Paek KY. 2007. Parameters affecting the extraction of ginsenosides from the adventitious roots of ginseng (Panax ginseng C.A. Meyer). Sep Purif Technol 56: 401-406 https://doi.org/10.1016/j.seppur.2007.06.014
  18. Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K. 2008. In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf B Biointerfaces 65: 1-10 https://doi.org/10.1016/j.colsurfb.2008.02.013
  19. Tandon S, Das M, Khanna SK. 1993. Effect of sanguinarine on the transport of essential nutrients in an everted gut sac model: role of $Na^+$, $K^+$-ATPase. Nat Toxins 1: 235-240 https://doi.org/10.1002/nt.2620010406
  20. Taga MS, Miller EE, Pratt DE. 1984. Chia seeds as a source of natural lipid antioxidants. J Am Oil Chem Soc 61: 928-931. https://doi.org/10.1007/BF02542169
  21. Dou D, Jin L, Chen Y. 1999. Advances and prospects of the study on chemical constituents and pharmacological activities of Panax ginseng. J Shen yang Pharm Univ 16: 151-156
  22. Luo ZY, Lu QH, Liu SP, Chen XH, Luo JQ, Tan LJ, Hu WX. 2003. Screening and identification of novel gens involved in biosynthesis of ginsenoside in Panax ginseng plant. ACTA Biochem Biophys Sin 35: 554-560
  23. Miller NJ, Ruiz-Larrea MB. 2002. Flavonoids and other plant phenols in the diet: what is their significance as antioxidants? J Nutr Environ Med 12: 39-51 https://doi.org/10.1080/13590840220123352
  24. Hutabarat LS, Greenfield H, Mulholland M. 2000. Quantitative determination of isoflavones and coumestrol in soybean by column liquid chromatography. J Chromatogr A 886: 55-63 https://doi.org/10.1016/S0021-9673(00)00444-1
  25. Pandjaitan N, Hettiarachchy N, Ju ZY. 2000. Enrichment of genistein in soy protein concentrate with ${\beta}-glucosidase$. Food Chem Toxicol 65: 403-407
  26. Karikura M, Miyase T, Tanizawa H, Takino Y, Taniyama T, Hayashi T. 1990. Studies on absorption, distribution, excretion and metabolism of ginseng saponins. V. The decomposition products of ginsenoside Rb2 in the large intestine of rats. Chem Pharm Bull 38: 2859-2861 https://doi.org/10.1248/cpb.38.2859
  27. Yoshikoshi M, Kahara T, Yoshiki Y, Ito M, Furukawa Y, Okubo K, Amarowicz R. 1995. Metabolism and nonabsorption of soybean hypocotyl saponins in the rat model. Acta Alimentaria 24: 355-364
  28. Flaoyen A, Wilkins AL, Deng D, Brekke T. 2001. Ovine metabolism of saponins: Evaluation of a method for estimating the ovine uptake of steroidal saponins from Narthecium ossifragum. Vet Res Commun 25: 225-238 https://doi.org/10.1023/A:1006485726523
  29. Lee SJ, Ko WG, Kim JH, Sung JH, Lee SJ, Moon CK, Lee BH. 2000. Induction of apoptosis by a novel intestinal metabolite of ginseng saponin via cytochrome c-mediated activation of caspase-3 protease. Biochem Pharmacol 60: 677-685 https://doi.org/10.1016/S0006-2952(00)00362-2
  30. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. 2000. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 63: 1702-1704 https://doi.org/10.1021/np990152b
  31. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert- Zsilavecz M. 2003. Degeneration of ginsenosides in humans after oral administration. Drug Metab Dispos 31: 1065-1071. https://doi.org/10.1124/dmd.31.8.1065
  32. Kanaoka M, Kato H, Shimada F, Yano S. 1992. Studies on the enzyme immuno-assay of bioactive constituents in oriental medicinal drugs VI: Enzyme immuno-assay of ginsenoside Rb-1 from Panax ginseng. Chem Pharm Bull 40: 314-317 https://doi.org/10.1248/cpb.40.314
  33. Akao T, Kida H, Kanaoka M, Hattori M, Kobashi K. 1998. Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J Pharm Pharmacol 50: 1155-1160 https://doi.org/10.1111/j.2042-7158.1998.tb03327.x

Cited by

  1. Protective Effects of Ginseng Leaf Extract Using Enzymatic Extraction Against Oxidative Damage of UVA-Irradiated Human Keratinocytes vol.173, pp.4, 2014, https://doi.org/10.1007/s12010-014-0886-2
  2. The bioavailability of red ginseng extract fermented by Phellinus linteus vol.37, pp.1, 2013, https://doi.org/10.5142/jgr.2013.37.108
  3. Effects of fermented ginseng extracts on tumor metastasis in mice vol.19, pp.6, 2010, https://doi.org/10.1007/s10068-010-0221-9
  4. Utilization of hydrolytic enzymes for the extraction of ginsenosides from Korean ginseng leaves vol.47, pp.3, 2012, https://doi.org/10.1016/j.procbio.2011.12.004
  5. Anti-obesity and anti-inflammatory effects of high hydrostatic pressure extracts of ginseng in high-fat diet induced obese rats vol.10, 2014, https://doi.org/10.1016/j.jff.2014.06.007
  6. A comparison between high hydrostatic pressure extraction and heat extraction of ginsenosides from ginseng (Panax ginseng CA Meyer) vol.91, pp.8, 2011, https://doi.org/10.1002/jsfa.4334
  7. Fermentation of Korean Red Ginseng by Lactobacillus plantarum M-2 and Its Immunological Activities vol.165, pp.5-6, 2011, https://doi.org/10.1007/s12010-011-9328-6
  8. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity vol.20, pp.4, 2015, https://doi.org/10.3746/pnf.2015.20.4.253
  9. Fermenting Red Ginseng Enhances Its Safety and Efficacy as a Novel Skin Care Anti-Aging Ingredient:In Vitroand Animal Study vol.15, pp.11, 2012, https://doi.org/10.1089/jmf.2012.2187
  10. Cosmetic Potential of Enzymatic Treated Ginseng Leaf vol.34, pp.3, 2010, https://doi.org/10.5142/jgr.2010.34.3.227