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Isolation and Structure Determination of a Cholesterol Esterase Inhibitor from Ganoderma lucidum

  • Kim, Shin-Duk (Department of Biological Engineering, Seokyung University)
  • Received : 2010.06.29
  • Accepted : 2010.07.28
  • Published : 2010.11.28

Abstract

Bioassay-guided fractionation of a methanol extract of Ganoderma lucidum gave a pure cholesterol esterase inhibitor. On the basis of spectroscopic analysis and comparison with data from the literature, the structure of this compound was identified as $5{\alpha},8{\alpha}$-epidioxyergosta-6,22-dien-$3{\bet}$-ol (compound I). This compound inhibited cholesterol esterase activity with an $IC_{50}$ value of $42{\mu}M$. Lineweaver-Burk plot analysis revealed that compound I is a noncompetitive inhibitor. The findings of this study suggest that compound I may be the active principle of the hypocholesterolemic effect of Ganoderma lucidum.

Keywords

References

  1. Bailey, J. M., L. Gallo, and J. Gillespie. 1995. Inhibition of dietary cholesterol ester absorption by 3-BCP, a suicide inhibitor of cholesterol esterase. Biochem. Soc. Trans. 23: 408S.
  2. Bhat, S. G. and H. L. Brockman. 1982. The role of cholesteryl ester hydrolysis and synthesis in cholesterol transport across rat intestinal mucosal membrane. A new concept. Biochem. Biophys. Res. Commun. 109: 486-492. https://doi.org/10.1016/0006-291X(82)91747-8
  3. Bojana, B., M. Berovic, J. Zhang, and L. Zhi-Bin. 2007. Ganoderma lucidum and its pharmaceutically active compounds. Biotech. Annu. Rev. 13: 265-301. https://doi.org/10.1016/S1387-2656(07)13010-6
  4. Cateni, F., B. Dolijak, M. Zacchigna, M. Anderluh, A. Piltaver, G. Scialino, and E. Banfi. 2007. New biologically active epidioxysterols from Stereum hirsutum. Bioorg. Med. Chem. Lett. 17: 6330-6334. https://doi.org/10.1016/j.bmcl.2007.08.072
  5. Gallo, L. L., S. B. Clark, S. Myers, and G. V. Vahouny. 1984. Cholesterol absorption in rat intestine: Role of cholesterol esterase and acyl coenzyme A:cholesterol acyltransferase. J. Lipid Res. 25: 604-612.
  6. Grundy, S. M. 1983. Absorption and metabolism of dietary cholesterol. Annu. Rev. Nutr. 3: 71-96. https://doi.org/10.1146/annurev.nu.03.070183.000443
  7. Hosie, L., L. D. Sutton, and D. M. Quinn. 1987. p-Nitrophenyl and cholesteryl-N-alkyl carbamates as inhibitors of cholesterol esterase. J. Biol. Chem. 262: 260-264.
  8. Howles, P. N., C. P. Carter, and D. Y. Hui. 1996. Dietary free and esterified cholesterol absorption in cholesterol esterase (bile salt-stimulated lipase) gene-targeted mice. J. Biol. Chem. 271: 7196-7202. https://doi.org/10.1074/jbc.271.12.7196
  9. Huang, Y. and D. Y. Hui. 1990. Metabolic fate of pancreasderived cholesterol esterase in intestine: An in vitro study using Caco-2 cells. J. Lipid Res. 31: 2029-2037.
  10. Hui, D. Y. 1996. Molecular biology of enzymes involved with cholesterol ester hydrolysis in mammalian tissues. Biochim. Biophys. Acta 1303: 1-14. https://doi.org/10.1016/0005-2760(96)00085-9
  11. Ikeda, I., R. Matsuoka, T. Hamada, K. Mitsui, S. Imabayashi, A. Uchino, et al. 2002. Cholesterol esterase accelerates intestinal cholesterol absorption. Biochim. Biophys. Acta 1571: 34-44. https://doi.org/10.1016/S0304-4165(02)00204-0
  12. Kim, D. H., S. J. Jung, I. S. Chung, Y. H. Lee, D. K. Kim, S. H. Kim, et al. 2005. Ergosterol peroxide from flowers of Erigeron annuus L. as an anti-atherosclerosis agent. Arch. Pharm. Res. 28: 541-545. https://doi.org/10.1007/BF02977755
  13. Krause, B. R., D. R. Sliskovic, M. Anderson, and R. Homan. 1998. Lipid-lowering effects of WAY-121898, an inhibitor of pancreatic cholesteryl ester hydrolase. Lipids 33: 489-498. https://doi.org/10.1007/s11745-998-0232-8
  14. Krzyczkowski, W., E. Malinowska, P. Suchocki, J. Kleps, M. Olejnik, and F. Herold. 2008. Isolation and quantitative determination of ergosterol peroxide in various edible mushroom species. Food Chem. 113: 351-355.
  15. Kuo, L. M., K.Y. Chen, S. Y. Hwang, J. L. Chen, Y. Y. Liu, C. C. Liaw, et al. 2005. DNA topoisomerase I inhibitor, ergosterol peroxide from Penicillium oxalicum. Planta Med. 71: 77-78. https://doi.org/10.1055/s-2005-837755
  16. Nam, K. S., Y. S. Jo, Y. H. Kim, J. W. Hyun, and H. W. Kim. 2001. Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes. Life Sci. 69: 229-237. https://doi.org/10.1016/S0024-3205(01)01125-0
  17. Paterson, R. R. M. 2006. Ganoderma - A therapeutic fungal biofactory. Phytochemistry 67: 1985-2001. https://doi.org/10.1016/j.phytochem.2006.07.004
  18. Shamir, R., W. J. Johnson, R. Zolfaghari, H. S. Lee, and E. A. Fisher. 1995. Role of bile salt-dependent cholesteryl ester hydrolase in the uptake of micellar cholesterol by intestinal cells. Biochemistry 34: 6351-6358. https://doi.org/10.1021/bi00019a013
  19. Yang, B. K., S. C. Jeong, and C. H. Song. 2002. Hypolipidemic effect of exo- and endo-biopolymers produced from submerged mycelial culture of Ganoderma lucidum in rats. J. Microbiol. Biotechnol. 12: 872-877.