Inhibition of $\alpha$-Glucosidase Activity by Quercetin

Quercetin에 의한 $\alpha$-glucosidase 활성 저해

  • Lee, Dong-Sun (Departments of Microbiology, Kyungpook National University) ;
  • Kim, Jong-Guk (Departments of Microbiology, Kyungpook National University) ;
  • Lee, Sang-Han (Departments of Food Science & Technology, Kyungpook National University)
  • Published : 2006.12.28

Abstract

Quercetin is a flavonoid molecule that is known to tie in various sources of natural products such as vegetables and fruits. It has been proven that quercetin plays a crucial role in the prevention of colon cancer as well as homeostasis as radical scavenger in human body. It is also well-known that glycosidases, including $\alpha$-glucosidase, are involved in a variety of degenerative metabolic disorders. In the course of screening useful $\alpha$-glucosidase inhibitors, we screened out quercetin as a $\alpha$-glucosidase inhibitor from chemical libraries. Quercetin was shown to be a reversible, slow-binding, and noncompetitive inhibitor of yeast a-glucosidase with a K$_i$ value of $6.3\times10^{-8}$ M when it was included with an enzyme mixture. Together, these results show that quercetin has potential in treating disorders including diabetes, although the further mechanistic study is needed.

Quercetin은 flavonoid 계통의 물질로서 자연계에서 채소나 과일에 매우 흔하다. 또한 인체에서는 radical scavenger로서 신체항상성 뿐만 아니라 직장암의 예방에도 중요한 역할을 한다. Glucosidase를 포함한 glycosidase는 많은 종류의 대사성 질환에 관련이 있다. 유용한 $\alpha$-glucosidase 저해제를 스크리닝 하던 중 chemical library로부터 quercetin을 선별하였다. Quercetin은 $\alpha$-glucosidase에 가역적으로, 느리게 결합하며, 비경쟁적인 저해제인데, $6.3\times10^{-8}$ M의 Ki값을 가진다. 이러한 결과는 비록 기전 연구가 더 필요하지만, quercetin이 당뇨병과 같은 퇴행성 질환을 치료할 수 있다는 잠재성을 보여주는 것이다.

Keywords

References

  1. Armada, L. J., A. D. Mackey, and J. F. Gregory III. 2002. Intestinal brush border membrane catalyzes hydrolysis of pyridoxine-5'-beta-D-glucoside and exhibits parallel developmental changes of hydrolytic activities toward pyridoxine-5'-beta-D-glucoside and lactose in rats. J. Nutr. 132: 2695-2699
  2. Doucet J. 2005. Use of antidiabetic drugs in elderly patients. Diabetes Metab. 2: 977-5S98-5S104
  3. Casey, R. C., T. R. Jr. Oegema, K. M. Skubitz, S. E. Pambuccian, S. M. Grindle, and A. P. Skubitz. 2003. Cell membrane glycosylation mediates the adhesion, migration, and invasion of ovarian carcinoma cells. Clin. Exp. Metastasis 20: 143-152 https://doi.org/10.1023/A:1022670501667
  4. Dove, A. 2002. Seeking sweet relief for diabetes. Nat. Biotechnol. 20: 977-981 https://doi.org/10.1038/nbt1002-977
  5. Fischer, P. B., G. B. Karlsson, T. D. Butters, R. A. Dwek, and F. M. Platt. 1996. N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with changes in antibody recognition of the V1/V2 region of gp120. J. Virol. 70: 7143-7152
  6. Fischer, P. B., G. B. Karlsson, R. A. Dwek, and F. M. Platt. 1996. N-butyldeoxynojirimycin-mediated inhibition of human immunodeficiency virus entry correlates with impaired gp120 shedding and gp41 exposure. J. Virol. 70: 7153-7160
  7. Gogas, H., F. Shapiro, C. Aghajanian, D. Fennelly, L. Almadrones, W. J. Hoskins, and D. R. Spriggs. 1996. The impact of diabetes mellitus on the toxicity of therapy for advanced ovarian cancer. Gynecol. Oncol. 61: 22-26 https://doi.org/10.1006/gyno.1996.0090
  8. Jenkins, D. J., R. H. Taylor, D. V. Goff, H. Fielden, J. J. Mis-iewicz, D. L. Sarson, S. R. Bloom, and K. G. Alberti. 1998. The anti-herpes simplex virus activity of n-docosanol includes inhibition of the viral entry process. Antiviral. Res. 40: 85-94 https://doi.org/10.1016/S0166-3542(98)00048-5
  9. Lee, D. S. and S. H. Lee. 2001. Genistein, a soy isoflavone, is a potent alpha-glucosidase inhibitor. FEBS Lett. 501: 84-86 https://doi.org/10.1016/S0014-5793(01)02631-X
  10. Peterson, G. 1995. Evaluation of the biochemical targets of quercetin in tumor cells. J. Nutr. 125(3 Suppl): 784S-789S
  11. Rosenstock, J., and P. Raskin. 1988. Hypertension in diabetes mellitus. Cardiol. Clin. 6: 547-560
  12. Santell, R. C., N. Kieu, and W. G. Helferich. 2000. Quercetin inhibits growth of estrogen-independent human breast cancer cells in culture but not in athymic mice. J. Nutr. 130: 1665-1669
  13. Segel, I. H. 1975. Enzyme kinetics: behavior and analysis of rapid equilibrium and steady-state enzyme system. Wiley, New York, p100-202
  14. Tadera K, Y. Minami, K. Takamatsu, and T. Matsuoka. 2006. Inhibition of alpha-glucosidase and alpha-amylase by flavonoids. J. Nutr. Sci. Vitaminol. (Tokyo). 52: 149-153 https://doi.org/10.3177/jnsv.52.149
  15. Tsujii, E., M. Muroi, N. Shiragami, and A. Takatsuki. 1996. Nectrisine is a potent inhibitor of alpha-glucosidases, demonstrating activities similarly at enzyme and cellular levels. Biochem. Biophys. Res. Commun. 220: 459-466 https://doi.org/10.1006/bbrc.1996.0427
  16. Walker, B. D., M. Kowalski, W. C. Goh, K. Kozarsky, M, Krieger, C. Rosen, L. Rohrschneider, W. A. Haseltine, and J. Sodroski. 1987. Inhibition of human immunodeficiency virus syncytium formation and virus replication by castanospermine. Proc. Natl. Acad. Sci. U.S.A. 84: 8120-8124
  17. de Groot H, and U. Rauen. 1998. Tissue injury by reactive oxygen species and the protective effects of flavonoids. Fundam. Clin. Pharmacol. 12: 249-255