DOI QR코드

DOI QR Code

Human Acyl-CoA: Cholesterol Acyltransferase (hACAT) Inhibitory Activities of Triterpenoids from Roots of Glycine max (L.) Merr

  • Lee, Jin-Hwan (Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University) ;
  • Ryu, Young-Bae (Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University) ;
  • Lee, Byong-Won (Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University) ;
  • Kim, Jin-Hyo (Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University) ;
  • Lee, Woo-Song (National Research Laboratory of Lipid Metabolism & Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Yong-Dae (National Research Laboratory of Lipid Metabolism & Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jeong, Tae-Sook (National Research Laboratory of Lipid Metabolism & Atherosclerosis, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Ki-Hun (Division of Applied Life Science (BK21 Program), EB-NCRC, Institute of Agriculture & Life Science, Graduate School of Gyeongsang National University)
  • 발행 : 2008.03.20

초록

Eight triterpenoids, six lanostanes 1-6, one lupenane 7, and one oleanane 8, were isolated by bioactivity-guided fractionation of the ethylacetate extract from roots of Glycine max (L.) Merr. All isolated compounds were examined for their inhibitory activities against human ACAT-1 (hACAT-1) and human ACAT-2 (hACAT-2). Among them, three triterpenoids showed potent hACAT inhibitory activities, (24R)-ethylcholest-5-ene-3,7-diol (1) and 3b -hydroxylup-20(29)-en-28-oic acid (7) exhibited more potent inhibitory activity against hACAT-1 (1: IC50 = 25.0 1.2 and 7: IC50 = 11.5 0.4 m M) than hACAT-2 (1: IC50 = 102.0 5.4 and 7: IC50 = 33.9 3.7 m M), respectively. Interestingly, 5a ,8a -epidioxy-24(R)-methylcholesta-6,22-diene-3b -ol (4) has proven to be a specific inhibitor against hACAT-1 (IC50 = 38.7 0.8 m M) compared to hACAT-2 (IC50 >200). In conclusion, this is the first study to demonstrate that triterpenoids of G. max have potent inhibitory activities against hACAT-1 and hACAT-2.

키워드

참고문헌

  1. Chang, T. Y.; Chang, C. C. Y.; Cheng, D. Annu. Rev. Biochem. 1997, 66, 613 https://doi.org/10.1146/annurev.biochem.66.1.613
  2. Ohgami, N.; Kuniyasu, A.; Furukawa, K.; Miyazaki, A.; Hakamata, H.; Horiuchi, S.; Nakayama, H. Biochem. Biophys. Res. Commun. 2000, 277, 412
  3. Doshi, R.; Wu, J.; Fishelevich, R.; Rodriguez, A. Expert. Opin. Ther. Patents 2001, 11, 1655 https://doi.org/10.1517/13543776.11.11.1655
  4. Joyce, C. W.; Shelness, G. S.; Davis, M. A.; Lee, R. G.; Skinner, K.; Anderson, R. A.; Rudel, L. L. Mol. Biol. Cell 2000, 11, 3675 https://doi.org/10.1091/mbc.11.11.3675
  5. Lee, R. G.; Willingham, M. C.; Davis, M. A.; Skinner, K. A.; Rudel, L. L. J. Lipid Res. 2000, 41, 1991
  6. Rudel, L. I.; Lee, R. G.; Cockman, T. L. Curr. Opin. Lipidol. 2001, 12, 121 https://doi.org/10.1097/00041433-200104000-00005
  7. Chang, T. Y.; Chang, C. C.; Lin, S.; Yu, C.; Li, B. L.; Miyazaki, A. Curr. Opin. Lipidol. 2001, 12, 289 https://doi.org/10.1097/00041433-200106000-00008
  8. Giovannoni, M. P.; Piaz, V. D.; Vergelli, C.; Barlocco, D. Mini-Rev. Med. Chem. 2003, 3, 576 https://doi.org/10.2174/1389557033487890
  9. Merz-Demlow, B.; Duncan, A.; Wangen, K.; Xu, X.; Carr, T.; Phippos, W.; Kurzer, M. Am. J. Chin. Nutr. 2000, 71, 1462 https://doi.org/10.1093/ajcn/71.6.1462
  10. Charron, C. S.; Allen, F. L.; Johnson, R. D.; Pantalone, V. R.; Sams, C. E. J. Agric. Food Chem. 2005, 53, 7128 https://doi.org/10.1021/jf050610o
  11. Yamaya, A.; Endo, Y.; Fujimoto, K.; Kitamura, K. Food Chem. 2007, 102, 1071 https://doi.org/10.1016/j.foodchem.2006.07.001
  12. Lee, J. H.; Baek, I. Y.; Ko, J. M.; Kang, N. S.; Kim, H. T.; Han, W. Y.; Shin, S. D.; Park, K. Y.; Oh, K. W.; Ha, T. J.; Park, K. H. J. Appl. Biol. Chem. 2007, 50, 63
  13. Tikkanen, M. J.; Wahala, K.; Ojala, S.; Vihma, V.; Adlercreutz, H. Proc. Natl. Acad. Sci. U.S.A. 1998, 95, 3106 https://doi.org/10.1073/pnas.95.6.3106
  14. Lee, C. H.; Yang, L.; Xu, J. Z.; Yeung, S. Y. V.; Huang, Y.; Chen, Z. Y. Food Chem. 2005, 90, 735 https://doi.org/10.1016/j.foodchem.2004.04.034
  15. Hendrich, S.; Lee, K. W.; Xu, X.; Wang, H. J.; Murphy, P. A. J. Nutr. 1994, 124, 1789S https://doi.org/10.1093/jn/124.suppl_9.1789S
  16. Anthony, M. S.; Clarkson, T. B.; Hughes, C. L.; Morgan, T. M.; Burke, G. L. J. Nutr. 1996, 126, 43 https://doi.org/10.1093/jn/126.1.43
  17. Lee, J. H.; Lee, B. W.; Kim, J. H.; Jeong, T. S.; Kim, M. J.; Lee, W. S.; Park, K. H. J. Agric. Food Chem. 2006, 54, 2057 https://doi.org/10.1021/jf052431c
  18. Lee, J. H.; Seo, K. I.; Kang, N. S.; Yang, M. S.; Park, K. H. Agric. Chem. Biotechnol. 2006, 49, 51
  19. Kvasnica, M.; Sarek, J.; Klinotova, E.; Dzubak, P.; Hajduch, M. Bioorg. Med. Chem. 2005, 13, 3447 https://doi.org/10.1016/j.bmc.2005.03.006
  20. Zhou, W. X.; Nes, W. D. Tetrahedron Lett. 2000, 41, 2791 https://doi.org/10.1016/S0040-4039(00)00265-3
  21. Zhang, Y.; Mills, G. L.; Nair, M. G. J. Agric. Food Chem. 2002, 50, 7581 https://doi.org/10.1021/jf0257648
  22. Singh, S. B.; Zink, D. L.; Dombrowski, A. W.; Polishook, J. D.; Ondeyka, J. G.; Hirshfield, J.; Felock, P.; Hazuda, D. J. Bioorg. Med. Chem. 2003, 11, 1577 https://doi.org/10.1016/S0968-0896(02)00529-1
  23. Sasaki, K.; Minowa, N.; Kuzuhara, H.; Nishiyama, S.; Omoto, S. Tetrahedron Lett. 1997, 38, 8335 https://doi.org/10.1016/S0040-4039(97)10256-8
  24. Nam, K. S.; Jo, Y. S.; Kim, Y. H.; Hyun, J. W.; Kim, H. W. Life Sci. 2001, 69, 229 https://doi.org/10.1016/S0024-3205(01)01125-0
  25. Macías, F. A.; Chinchilla, N.; Varela, R. M.; Molinillo, J. M. G. Steroids 2006, 71, 603 https://doi.org/10.1016/j.steroids.2006.03.001
  26. Kim, S. W.; Park, S. S.; Min, T. J.; Yu, K. H. Bull. Korean Chem. Soc. 1999, 20, 819 https://doi.org/10.1007/BF02697282
  27. Chung, I. M.; Park, H. Y.; Ali, M.; San, K. Y.; Peebles, C. A. M.; Hong, S. B.; Ahmad, A. Bull. Korean Chem. Soc. 2007, 28, 229 https://doi.org/10.5012/bkcs.2007.28.2.229
  28. Hu, H. B.; Zheng, X. D.; Hu, H. S.; Jian, Y. E. Bull. Korean Chem. Soc. 2007, 28, 1519 https://doi.org/10.5012/bkcs.2007.28.9.1519
  29. Cho, K. H.; An, S.; Lee, W. S.; Paik, Y. K.; Kim, Y. K.; Jeong, T. S. Biochem. Biophys. Res. Commun. 2003, 309, 864 https://doi.org/10.1016/j.bbrc.2003.08.077
  30. Lee, W. S.; Im, K. R.; Park, Y. D.; Sung, N. D.; Jeong, T. S. Biol. Pharm. Bull. 2006, 29, 382 https://doi.org/10.1248/bpb.29.382
  31. Lee, C. H.; Jeong, T. S.; Choi, Y. K.; Hyun, B. W.; Oh, G. T.; Kim, E. H.; Kim, J. R.; Han, J. I.; Bok, S. H. Biochem. Biophys. Res. Commun. 2001, 284, 681 https://doi.org/10.1006/bbrc.2001.5001

피인용 문헌

  1. Synthesis, biology and clinical significance of pentacyclic triterpenes: a multi-target approach to prevention and treatment of metabolic and vascular diseases vol.28, pp.3, 2011, https://doi.org/10.1039/c0np00059k