A study on separation and characterization of matrix metalloproteinase-9 inhibitors from natural plants

천연 식물 추출물에서 Matrix Metalloproteinase-9 활성 억제제의 분리 및 특성화에 관한 연구

  • Hur, Yong-Chul (Department of Chemical Engineering, Suwon University) ;
  • Park, Sung-Woo (National Institute of Scientific Investigation) ;
  • Kim, Tai-Jin (Department of Chemical Engineering, Suwon University)
  • Received : 2003.12.24
  • Accepted : 2005.05.02
  • Published : 2005.06.25


Three different oriental natural plants (Angelicae Dahuricae Radix, Sanguisorba Officinalis L, Euonymus alatus) were extracted with 70% methanol under refluxing for 4 hr in order to investigate their inhibitory effect on Matrix Metalloproteinase-9 (MMP-9) by a modified gelatin zymography, where only euonymus alatus showed the inhibitory effect on the activity of Matrix MMP-9. The fraction was collected by using the mixture of ethyl acetate and hexane on silica gel column. Seven portions were obtained and three fractions of them (first, third and forth) showed inhibitory effect on the zymography. To verify the effect of these substances on cells, human hepatoma, Hep3B cells as a cancer model, and Chang liver cells as a normal model were selected. In order to examine the cell viability, $1{\mu}g/mL$ of each extract was treated on cells. Most of the methanol soluble fractions showed negligible toxicity on human liver cell line.


  1. U. B. Hofmann, J. R. Westphal, G. N. P. Van Muijen, and D. J. Ruiter, J. Invest. Dermatol. 115, 337-344(2000) https://doi.org/10.1046/j.1523-1747.2000.00068.x
  2. D. E. Kleiner and W. G. Stetler-Stevenson, Curr. Opinion Cell Biol. 5, 891-897(1993) https://doi.org/10.1016/0955-0674(93)90040-W
  3. G. Opdenakker, P. E. Van den Steen, and J. Van Damme, Trends Immunol., 22, 571-579(2001) https://doi.org/10.1016/S1471-4906(01)02023-3
  4. T. A. Butler, C. Zhu, R. A. Mueller, G. C. Fuller, W. L. Lemaire, and J. F. Woessner, J. Biol. Reprod., 44, 1183-1188(1991) https://doi.org/10.1095/biolreprod44.6.1183
  5. C. H. Graham and P. K. Lala, J. Cell Physiol., 148, 228-234(1991) https://doi.org/10.1002/jcp.1041480207
  6. S. Gack, R. Vallon, J. A. Schmidt, J. Tuckermann, J. Schenkel, H. Weiher, and P. Angel, Cell Growth Differ., 6, 759-767(1995)
  7. L. R. Lund, J. Romer, N. Thomasset, H. Solberg, C. Pyke, M. J. Bissell, K. Dano, and Z. Werb, Development 122, 181-193(1996)
  8. S. Stetler, J. Clin. Invest. 103, 1237-1241(1999) https://doi.org/10.1172/JCI6870
  9. T. E. Cawston, Pharmacol. Ther. 70, 163-182(1996). https://doi.org/10.1016/0163-7258(96)00015-0
  10. L. Liotta, P. S. Steeg, and W. G. Stetler-Stevenson, Cell 64, 327-336(1991) https://doi.org/10.1016/0092-8674(91)90642-C
  11. S. K. Chandler, R. E. Coates, A. Gearing, J. Lury, and E. A. Bone, Neurosci. Lett. 201, 223-226(1995) https://doi.org/10.1016/0304-3940(95)12173-0
  12. 이정호, 김하군, 하대유, Korean J. Immunol, 15, 243-253(1993)
  13. 이정호, 신숙정, 문용, 이동근, Korean J., Immunol. 18, 253-263(1996)
  14. Chung, Hwan-Suck, Jeong, Hyun-Ja, etc, Clinica Chimica Acta, 318(1-2), 113-120(2002) https://doi.org/10.1016/S0009-8981(01)00808-7
  15. He, Lan, Lu, Shu-Ming, Pan, Yuan-Jiang, Chen, and Yao-Zu, J. of Zhejiang Univ. Science, 1, 188-189(2000) https://doi.org/10.1631/jzus.2000.0188
  16. Ishikura, Nariyuki and Yang, Zhi-Qing, Phytochemistry, 36, 1139-1145(1994) https://doi.org/10.1016/S0031-9422(00)89627-2
  17. Ishikura, Nariyuki and Yang, Zhi-Qing, J. of Biosciences, 46, 1003-1010(1991)
  18. Tazaki, Kiyoshi and Ishikura, Nariyuki, Plant and Cell Physiology, 26, 721-728(1985) https://doi.org/10.1093/oxfordjournals.pcp.a076962
  19. Chen, Ke, Pan, Deji, and Xu, Guangyi, Zhongcaoyao, 17, 97-100(1986)
  20. Ishiwata, Hiroyuki, Shizuri, Yoshikazu, and Yamada, Kiyoyuki, Phytochemistry, 22, 2839-2841(1983) https://doi.org/10.1016/S0031-9422(00)97709-4
  21. K. Yamada, Y. Shizuri, and Y. Hirata, Tetrahedron, 34, 1915-1920(1978) https://doi.org/10.1016/0040-4020(78)80097-0
  22. Ishikura, Nariyuki and Sato, Shuji, Botanical Magazine, Tokyo, 70, 83-87(1977)
  23. Sugiura, Kimio, Shizuri, Yoshikazu, Yamade, Kiyoyuki, and Hirata, Yoshimasa, Tetrahedron Letters, 27, 2307-2310(1975)
  24. Sugiura, Kimio, Shizuri, Yoshikazu, Yamade, Kiyoyuki, and Hirata, Yoshimasa, Chemistry Letters, 5, 471-472(1975)
  25. C. Heussen and E. B. Dowdle, Anal. Biochem., 102, 196-202(1980) https://doi.org/10.1016/0003-2697(80)90338-3
  26. L. I. Lin, Y. F. Ke, Y. C. Ko, and J. K. Lin, Oncology, 55, 349-353(1998) https://doi.org/10.1159/000011876
  27. S. K. Kim, Y. H. Lee, J. H. Park, and S. K. Lee, Ginsenoside-Rs4, Eur. J. of Cancer, 35, 507-511(1999) https://doi.org/10.1016/S0959-8049(98)00415-8