Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

  • Lee, Je Hyeong (College of Pharmacy, Kangwon National University) ;
  • Shehzad, Omer (College of Pharmacy, Seoul National University) ;
  • Ko, Sung Kwon (Department of Oriental Medical Food and Nutrition, Semyung University) ;
  • Kim, Yeong Shik (College of Pharmacy, Seoul National University) ;
  • Kim, Hyun Pyo (College of Pharmacy, Kangwon National University)
  • Received : 2014.05.01
  • Accepted : 2014.06.25
  • Published : 2015.01.15
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Abstract

Background: The present study was designed to prepare and find the optimum active preparation or fraction from Korea Red Ginseng inhibiting matrix metalloproteinase-13 (MMP-13) expression, because MMP-13 is a pivotal enzyme to degrade the collagen matrix of the joint cartilage. Methods: From total red ginseng ethanol extract, n-BuOH fraction (total ginsenoside-enriched fraction), ginsenoside diol-type-enriched fraction (GDF), and ginsenoside triol-type-enriched fraction (GTF) were prepared, and ginsenoside diol type-/F4-enriched fraction (GDF/F4) was obtained from Panax ginseng leaf extract. Results: The n-BuOH fraction, GDF, and GDF/F4 clearly inhibited MMP-13 expression compared to interleukin-$1{\beta}$-treated SW1353 cells (human chondrosarcoma), whereas the total extract and ginsenoside diol-type-enriched fraction did not. In particular, GDF/F4, the most effective inhibitor, blocked the activation of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun-activated protein kinase (JNK), and signal transducer and activator of transcription-1/2 (STAT-1/2) among the signal transcription pathways involved. Further, GDF/F4 also inhibited the glycosaminoglycan release from interleukin-$1{\alpha}$-treated rabbit cartilage culture (30.6% inhibition at $30{\mu}g/mL$). Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

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References

  1. Roughley PJ. The structure and function of cartilage proteoglycans. Eur Cell Mater 2006;12:92-101. https://doi.org/10.22203/eCM.v012a11
  2. Hadler-Olsen E, Fadnes B, Sylte I, Uhlin-Hansen L, Winberg JO. Regulation of matrix metalloproteinase activity in health and disease. FEBS J 2011;278: 28-45. https://doi.org/10.1111/j.1742-4658.2010.07920.x
  3. Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, Geoghegan KF, Hambor JE. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest 1996;97:761-8. https://doi.org/10.1172/JCI118475
  4. Takaishi H, Kimura T, Dalah S, Okada Y, D'Armiento J. Joint disease and matrix metalloproteinases: a role for MMP-13. Curr Pharmacol Biotechnol 2008;9: 47-54. https://doi.org/10.2174/138920108783497659
  5. Wu JY, Gardner BH, Murphy CI, Seals JR, Kensil CR, Recchia J, Beltz GA, Newman GW, Newman MJ. Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. J Immunol 1992;148:1519-25.
  6. Mochizuki M, Yoo CY, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I. Inhibitory effect of tumor metastasis in mice by saponins, ginsenosides 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
  7. Nag SA, Qin JJ, Wang W, Wang MH, Wang H, Zhang R. Ginsenosides as anticancer agents: in vitro and in vivo activities, structure-activity relationships, and molecular mechanisms of action. Front Pharmacol 2012;3:25.
  8. Shehzad O, Khan S, Ha IJ, Park Y, Kim YS. Rational development of selection model for solvent gradients in single step separation of ginsenosides from Panax ginseng using high-speed counter-current chromatography. J Sep Sci 2012;35:1462-9. https://doi.org/10.1002/jssc.201200135
  9. Shehzad O, Kim HP, Kim YS. State-of-the art separation of ginsenosides from Korean white and red ginseng by countercurrent chromatography. Anal Bioanal Chem 2013;405:4523-30. https://doi.org/10.1007/s00216-012-6609-z
  10. So MW, Lee EJ, Lee HS, Koo BS, Kim YG, Lee CK, Yoo B. Protective effects of ginsenoside Rg3 on human osteoarthritic chondrocytes. Mod Rheumatol 2013;23:104-11. https://doi.org/10.3109/s10165-012-0635-8
  11. Lee JH, Lim H, Shehzad O, Kim YS, Kim HP. Ginsenosides from Korean red ginseng inhibit matrix metalloproteinase-13 expression in articular chondrocytes and prevent cartilage degradation. Eur J Pharmacol 2014;724:145-51. https://doi.org/10.1016/j.ejphar.2013.12.035
  12. Lim H, Kim HP. Matrix metalloproteinase-13 expression in IL-1${\beta}$-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways. Arch Pharm Res 2011;34:109-17. https://doi.org/10.1007/s12272-011-0113-4
  13. Mossman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays. J Immunol Methods 1983;65:55-63. https://doi.org/10.1016/0022-1759(83)90303-4
  14. Mengshol JA, Vincenti MP, Coon CI, Barchowsky A, Brincherhoff CE. Interleukin- 1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor ${\kappa}B$: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 2000;43:801-11. https://doi.org/10.1002/1529-0131(200004)43:4<801::AID-ANR10>3.0.CO;2-4
  15. Wang CZ, Aung HH, Ni M, Wu JA, Tong R, Wicks S, He TC, Yuan CS. Red American ginseng: ginsenosides constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. Planta Med 2007;73:669-74. https://doi.org/10.1055/s-2007-981524

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