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Enzymatic transformation of ginsenosides in Korean Red Ginseng (Panax ginseng Meyer) extract prepared by Spezyme and Optidex

  • Choi, Hyeon-Son (Department of Food and Nutrition, Korea University) ;
  • Kim, Sun Young (Department of Efficacy Screening, Hongcheon Institute of Medicinal Herb) ;
  • Park, Yooheon (Department of Food and Nutrition, Korea University) ;
  • Jung, Eun Young (Department of Home Economic Education, Jeonju University) ;
  • Suh, Hyung Joo (Department of Food and Nutrition, Korea University)
  • Received : 2013.11.28
  • Accepted : 2014.03.24
  • Published : 2014.10.15

Abstract

Background: In this study, we examined the effects of various enzymes on chemical conversions of ginsenosides in ginseng extract prepared by amylases. Methods: Rapidase, Econase CE, Viscozyme, Ultraflo L, and Cytolase PCL5 were used for secondary enzymatic hydrolysis after amylase treatment of ginseng extract, and ginsenoside contents, skin permeability, and chemical compositions including total sugar, acidic polysaccharide, and polyphenols were determined on the hydrolyzed ginseng extract. Results: Rapidase treatment significantly elevated total ginsenoside contents compared with the control (p < 0.05). In particular, deglycosylated ginsenosides including Rg3, which are known as bioactive compounds, were significantly increased after Rapidase treatment (p < 0.05). The Rapidase-treated group also increased the skin permeability of polyphenols compared with the control, showing the highest level of total sugar content among the enzyme treatment groups. Conclusion: This result showed that Rapidase induced the conversion of ginsenoside glycosides to aglycones. Meanwhile, Cytolase PCL5 and Econase treatments led to a significant increase of uronic acid (acidic polysaccharide) level. Taken together, our data showed that the treatments of enzymes including Rapidase are useful for the conversion and increase of ginsenosides in ginseng extracts or products.

Keywords

References

  1. Ernst E. Panax ginseng: an overview of the clinical evidence. J Ginseng Res 2010;34:259-63. https://doi.org/10.5142/jgr.2010.34.4.259
  2. Furuya T, Kojima H, Syono K, Ishii T, Uotani K. Isolation of saponins and sapogenins from callus tissue of Panax ginseng. Chem Pharm Bull (Tokyo) 1973;21:98-101. https://doi.org/10.1248/cpb.21.98
  3. Park JS, Park EM, Kim DH, Jung K, Jung JS, Lee EJ, Hyun JW, Kang JL, Kim HS. Anti-inflammatory mechanism of ginseng saponins in activated microglia. J Neuroimmunol 2009;209:40-9. https://doi.org/10.1016/j.jneuroim.2009.01.020
  4. Surh YJ, Na HK, Lee JY, Keum YS. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16(Suppl.):S38-41. https://doi.org/10.3346/jkms.2001.16.S.S38
  5. Park D, Bae DK, Jeon JH, Lee J, Oh N, Yang G, Yang YH, Kim TK, Song J, Lee SH, et al. Immunopotentiation and antitumor effects of a ginsenoside Rg(3)-fortified red ginseng preparation in mice bearing H460 lung cancer cells. Environ Toxicol Pharmacol 2011;31:397-405. https://doi.org/10.1016/j.etap.2011.01.008
  6. Kim YS, Kim JJ, Cho KH, Jung WS, Moon SK, Park EK, Kim DH. Biotransformation of ginsenoside Rb1, crocin, amygdalin, geniposide, puerarin, ginsenoside Re, hesperidin, poncirin, glycyrrhizin, and baicalin by human fecal microflora and its relation to cytotoxicity against tumor cells. J Microbiol Biotechnol 2008;18:1109-14.
  7. Bae E-A, Han MJ, Choo M-K, Park S-Y, Kim D-H. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002;25:58-63. https://doi.org/10.1248/bpb.25.58
  8. Bae EA, Kim NY, Myung JH, Choo MK, Kim DH. Transformation of ginsenosides to compound K (IH-901) by lactic acid bacteria of human intestine. J Microbiol Biotechnol 2003;13:9-14.
  9. Kim BG, Shin KS, Yoon TJ, Yu KW, Ra KS, Kim JM, Kim SY, Suh HJ. Fermentation of Korean red ginseng by Lactobacillus plantarum M-2 and its immunological activities. Appl Biochem Biotechnol 2011;165:1107-19. https://doi.org/10.1007/s12010-011-9328-6
  10. Su J-H, Xu J-H, Lu W-Y, Lin G-Q. Enzymatic transformation of ginsenoside $Rg_3$ to $Rh_2$ using newly isolated Fusarium proliferatum ECU2042. J Mol Catal B Enzymat 2006;38:113-8. https://doi.org/10.1016/j.molcatb.2005.12.004
  11. Popovich DG, Kitts DD. Generation of ginsenosides Rg3 and Rh2 from North American ginseng. Phytochemistry 2004;65:337-44. https://doi.org/10.1016/j.phytochem.2003.11.020
  12. Bae SH, Lee HS, Kim MR, Kim SY, Kim JM, Suh HJ. Changes of ginsenoside content by mushroom mycelial fermentation in red ginseng extract. J Ginseng Res 2011;35:235-42. https://doi.org/10.5142/jgr.2011.35.2.235
  13. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M. Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 2003;31:1065-71. https://doi.org/10.1124/dmd.31.8.1065
  14. Han BH, Park MH, Han YN, Woo LK, Sankawa U, Yahara S, Tanaka O. Degradation of ginseng saponins under mild acidic conditions. Planta Med 1982;44:146-9. https://doi.org/10.1055/s-2007-971425
  15. Ko SR, Choi KJ, Uchida K, Suzuki Y. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1 from protopanaxatriol-type ginseng saponin mixture. Planta Med 2003;69:285-6. https://doi.org/10.1055/s-2003-38476
  16. Park CS, Yoo MH, Noh KH, Oh DK. Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl Microbiol Biotechnol 2010;87:9-19. https://doi.org/10.1007/s00253-010-2567-6
  17. Kim B-G, Choi SY, Suh HJ, Park HJ. Bitterness reduction and enzymatic transformation of ginsenosides from Korean red ginseng (Panax ginseng) extract. J Food Biochem 2011;35:1267-82. https://doi.org/10.1111/j.1745-4514.2010.00450.x
  18. Dubois M, Gilles KA, Hamilton JK, Rebers P, Smith F. Colorimetric method for determination of sugars and related substances. Anal Chem 1956;28:350-6. https://doi.org/10.1021/ac60111a017
  19. Blumenkrantz N, Asboe-Hansen G. New method for quantitative determination of uronic acids. Anal Biochem 1973;54:484-9. https://doi.org/10.1016/0003-2697(73)90377-1
  20. Singleton VL, Orthofer R, Lamuela-Raventos RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of Foline-Ciocalteu reagent. Methods Enzymol 1999;299:152-78. https://doi.org/10.1016/S0076-6879(99)99017-1
  21. Lou D-W, Saito Y, Jinno K. Solid-phase extraction and high-performance liquid chromatography for simultaneous determination of important bioactive ginsenosides in pharmaceutical preparations. Chromatographia 2005;62:349-54. https://doi.org/10.1365/s10337-005-0640-6
  22. Lee HJ, Jung EY, Lee H-S, Kim B-G, Kim JH, Yoon TJ, Oh SH, Suh HJ. Bioavailability of fermented Korean red ginseng. J Food Sci Nutr 2009;14:201-7. https://doi.org/10.3746/jfn.2009.14.3.201
  23. Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K. In vitro permeation of gold nanoparticles through rat skin and rat intestine: effect of particle size. Colloids Surf B Biointerfaces 2008;65:1-10. https://doi.org/10.1016/j.colsurfb.2008.02.013
  24. Van Q, Nayak B, Reimer M, Jones P, Fulcher R, Rempel C. Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay. J Ethnopharmacol 2009;125:487-93. https://doi.org/10.1016/j.jep.2009.06.026
  25. Oh SH. Effect of fat soluble ginseng extract on lipolysis in vitro and in vivo. Korean Biochem J 1984;17:209-14.
  26. Ko S-R, Suzuki Y, Suzuki K, Choi K-J, Cho B-G. Marked production of ginsenosides Rd, F2, Rg3, and compound K by enzymatic method. Chem Pharm Bull (Tokyo) 2007;55:1522-7. https://doi.org/10.1248/cpb.55.1522
  27. Tang QN. Inventor; Extraction of phytochemicals by enzymatic hydrolysis. WO2008092275 A1; August 7, 2008.
  28. Park KM, Kim YS, Jeong TC, Joe CO, Shin HJ, Lee YH, Nam KY, Park JD. Nitric oxide is involved in the immunomodulating activities of acidic polysaccharide from Panax ginseng. Planta Med 2001;67:122-6. https://doi.org/10.1055/s-2001-11508
  29. Du XF, Jiang CZ, Wu CF, Won EK, Choung SY. Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression. Arch Pharm Res 2008;31:1153-9. https://doi.org/10.1007/s12272-001-1282-6
  30. Kwak Y-S, Kyung J-S, Kim JS, Cho JY, Rhee M-H. Anti-hyperlipidemic effects of red ginseng acidic polysaccharide from Korean red ginseng. Biol Pharm Bull 2010;33:468-72. https://doi.org/10.1248/bpb.33.468
  31. Dixon RA, Paiva NL. Stress-induced phenylpropanoid metabolism. Plant Cell 1995;7:1085-97. https://doi.org/10.1105/tpc.7.7.1085
  32. Sorensen HR, Pedersen S, Vikso-Nielsen A, Meyer AS. Efficiencies of designed enzyme combinations in releasing arabinose and xylose from wheat arabinoxylan in an industrial ethanol fermentation residue. Enzyme Microb Technol 2005;36:773-84. https://doi.org/10.1016/j.enzmictec.2005.01.007
  33. Landbo AK, Meyer AS. Enzyme-assisted extraction of antioxidative phenols from blackcurrant juice press residues (Ribes nigrum). J Agric Food Chem 2001;49:3169-77. https://doi.org/10.1021/jf001443p
  34. Le Bourvellec C, Guyot S, Renard C. Interactions between apple (Malus x domestica Borkh.) polyphenols and cell walls modulate the extractability of polysaccharides. Carbohydr Polym 2009;75:251-61. https://doi.org/10.1016/j.carbpol.2008.07.010
  35. Yu H, Zhang C, Lu M, Sun F, Fu Y, Jin F. Purification and characterization of new special ginsenosidase hydrolyzing multi-glycisides of protopanaxadiol ginsenosides, ginsenosidase type I. Chem Pharm Bull (Tokyo) 2007;55:231-5. https://doi.org/10.1248/cpb.55.231
  36. Bae E-A, Park S-Y, Kim D-H. Constitutive-glucosidases hydrolyzing ginsenoside Rb-1 and Rb-2 from human intestinal bacteria. Biol Pharm Bull 2000;23:1481-5. https://doi.org/10.1248/bpb.23.1481
  37. Shinkai K, Akedo H, Mukai M, Imamura F, Isoai A, Kobayashi M, Kitagawa I. Inhibition of in vitro tumor cell invasion by ginsenoside Rg3. Jpn J Cancer Res 1996;87:357-62. https://doi.org/10.1111/j.1349-7006.1996.tb00230.x
  38. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20 (R)-and 20 (S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull 1995;18:1197-202. https://doi.org/10.1248/bpb.18.1197
  39. Li X, Guan Y, Zhou X, Sun L, Liu Y, He Q, Fu L, Mao Y. Anticarcinogenic effect of 20 (R)-ginsenoside Rg3 on induced hepatocellular carcinoma in rats. Sichuan Da Xue Xue Bao Yi Xue Ban 2005;36:217-20.
  40. Lee H-U, Bae E-A, Han MJ, Kim D-H. Hepatoprotective effect of 20(S)-ginsenosides Rg3 and its metabolite 20(S)-ginsenoside Rh2 on tert-butyl hydroperoxide-induced liver injury. Biol Pharm Bull 2005;28:1992-4. https://doi.org/10.1248/bpb.28.1992
  41. He B, Chen P, Yang J, Yun Y, Zhang X, Yang R, Shen Z. Neuroprotective effect of 20(R)-ginsenoside Rg(3) against transient focal cerebral ischemia in rats. Neurosci Lett 2012;526:106-11. https://doi.org/10.1016/j.neulet.2012.08.022
  42. Kim ND, Kim EM, Kang KW, Cho MK, Choi SY, Kim SG. Ginsenoside Rg3 inhibits phenylephrine-induced vascular contraction through induction of nitric oxide synthase. Br J Pharmacol 2003;140:661-70. https://doi.org/10.1038/sj.bjp.0705490
  43. Cheng LQ, Na JR, Bang MH, Kim MK, Yang DC. Conversion of major ginsenoside Rb1 to 20(S)-ginsenoside Rg3 by Microbacterium sp. GS514. Phytochemistry 2008;69:218-24. https://doi.org/10.1016/j.phytochem.2007.06.035
  44. Kohda H, Tanaka O. Enzymatic hydrolysis of ginseng saponins and their related glycosides. Yakugaku Zasshi 1975;95:246-9. https://doi.org/10.1248/yakushi1947.95.2_246
  45. Do Y-K, Kim J-M, Chang S-M, Hwang J-H, Kim W-S. Enhancement of polyphenol bio-activities by enzyme reaction. J Mol Catal B Enzymat 2009;56:173-8. https://doi.org/10.1016/j.molcatb.2008.08.003
  46. Miller NJ, Ruiz-Larrea MB. Flavonoids and other plant phenols in the diet: their significance as antioxidants. J Nutr Environ Med 2002;12:39-51. https://doi.org/10.1080/13590840220123352
  47. Wiechers JW. The barrier function of the skin in relation to percutaneous absorption of drugs. Pharm Weekbl Sci 1989;11:185-98. https://doi.org/10.1007/BF01959410
  48. Bos JD, Meinardi MM. The 500 Dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol 2000;9:165-9. https://doi.org/10.1034/j.1600-0625.2000.009003165.x

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