The Inhibitory Effect of Cornus walteri Extract Against ${\alpha}-amylase$

말채나무 추출물의 ${\alpha}-amylase$ 저해 활성

  • Lim, Chae-Sung (Division of Biotechnology, Kangwon National University) ;
  • Li, Chun-Ying (Division of Biotechnology, Kangwon National University) ;
  • Kim, Yong-Mu (Division of Biotechnology, Kangwon National University) ;
  • Lee, Wi-Young (Korea Forest Research Institute) ;
  • Rhee, Hae-Ik (Division of Biotechnology, Kangwon National University)
  • Published : 2005.03.31

Abstract

${\alpha}-Amylase$ inhibitor is used to control blood glucose level by inhibiting starch digestion in the small intestine and delaying the absorption of glucose. In this study, we investigated the effect of the ethanol extracts from more than 1400 species of plants against ${\alpha}-amylase$ with the aim of developing a new ${\alpha}-amylase$ inhibitor. In the results, Cornus walteri extracts showed the highest inhibition activity. The inhibitory effect of Cornus walteri extract on the carbohydrate hydrolysis enzymes has different sensitivities against ${\alpha}-amylase$ from salivary and pancreatin and against ${\alpha}-glucosidase$ from yeast and porcine small intestine. In the study of inhibition kinetics of ${\alpha}-amylase$ and ${\alpha}-glucosidase$, Cornus walteri extract showed competitive inhibition against salivary and pancreatin while showing the combination of uncompetitive and noncompetitive inhibition against ${\alpha}-glucosidase$. The Cornus walteri extract was stable at acidic and thermal conditions. As for the blood glucose and body weight levels of Cornus walteri extract, we confirmed anti-hyperglycemic and anti-obesity effects. Also, in the investigation of the mRNA lever, Cornus walteri extract upregulated the level of GLUT4 mRNA in the quadriceps muscle.

${\alpha}-Amylase$ 저해제는 소장에서 전분의 소화를 저해하여 포도당의 흡수를 지연시킴으로써 혈당 조절 목적으로 이용된다. 따라서 본 연구에서는 ${\alpha}-amylase$ 저해제를 탐색할 목적으로 국내 자생 목본류 약 1400여종의 70% ethanol 추출액을 대상으로 ${\alpha}-amylase$ 저해제 분포를 검색하였다. 수종의 목본류에서 ${\alpha}-amylase$ 저해제가 분포하고 있음이 확인되었으며, 그 중 활성이 비교적 높은 말채나무 기원의 저해제를 대상으로 연구를 진행하였다. 기원별 효소에 따른 저해 활성도를 살펴보면 salivary와 pancreatic ${\alpha}-amylase$, 미생물 기원의 ${\alpha}-glucosidase$에는 탁월한 저해 활성을 보인 반면 돼지 기원의 ${\alpha}-glucosidase$ 저해제에 대해서는 매우 낮은 저해 활성을 보였다. ${\alpha}-Amylase$${\alpha}-glucosidase$의 kinetic을 분석하면 salivary와 pancreatic 두 효소에 모두 경쟁적 저해제로, 효모의 ${\alpha}-glucosidase$에는 비경쟁적과 반경쟁적의 혼합형 저해제로 나타났다. 또한 열과 산성에 대한 안정성을 확인한 결과 비교적 안정적인 것으로 나타났다. 본 추출물의 식이 섭취에 따른 혈당 강하 효과와 체중에 미치는 영향에서는 혈당과 체중 상승을 억제하는 효과가 확인되었고, mRNA수준에서 대퇴근 세포에 있어서 GLUT4의 발현이 증가됨을 확인하였다.

Keywords

References

  1. King, H., Aubert, R. E. and Herman, W. H. (1998) Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 21, 1414-1431 https://doi.org/10.2337/diacare.21.9.1414
  2. Stratton, I. M., Adler, A. I., Neil, H. A., Matthews, D. R., Manley, S. E., Cull, C. A., Hadden, D., Turner, R. C. and Holman, R. R. (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321, 405-412 https://doi.org/10.1136/bmj.321.7258.405
  3. Lebovitz, H. E. (2001) Effect of the postprandial state on nontraditional risk factors. Amer. J. Cardio. 88, 20-25
  4. Saito, N., Sakai, H., Sekihara, H. and Yajima, Y. (1998) Effect of an $\alpha -glucosidase$ inhibitor (voglibose), in combination with sulphonilureas, on glycaemic control in type 2 diabetes patients. J. Int. Med. Res. 26, 219-232
  5. Puls, W. and Keup, U. (1973) Influence of an $\alpha -amylase $ inhibitor (Bay d7791) on blood glucose, serum insulin and NEFF in starch loading tests in rats, dogs and man. Diabetologia 9, 97-101 https://doi.org/10.1007/BF01230687
  6. Toeller, M. (1994) ${alpha}$-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. Eur. J. Clin. Invest. 24, 31-35 https://doi.org/10.1111/j.1365-2362.1994.tb02253.x
  7. Rhinehart, B. L., Robinson, K. M., Liu, P. S., Payne, A. J., Wheatley, M. E. and Wanger, S. R. (1987) Inhibition of intestinal disaccharidase and suppression of blood glucose by a new ${\alpha}-glucohydrolase$ inhibitor-MDL 25, 637. J. Pham. Exp. Ther. 241, 915-920
  8. Lebovitz, H. E. (1998) Postprandial hyperglycemic state: importance and consequences. Diabetes Res. Clin. Pr. 40, 27-37 https://doi.org/10.1016/S0168-8227(98)00039-4
  9. Kim, Y. M., Wang M. H. and Rhee H. I. (2004) A novel ${\alpha}-glucosidase$ inhibitor from pine bark. Carbohydrate Res. 339, 715-717 https://doi.org/10.1016/j.carres.2003.11.005
  10. Hanozet, G., Pircher, H. P., Vanni, P., Oesch, B. and Semenza, G. (1981) An example of enzyme hysteresis. J. Biol. Chem. 256, 3703-3711
  11. Samulitis, B. K., Goda, T., Lee, S. M. and Koldovsky, O. (1987) Inhibitory mechanism of Acarbose and 1- deoxynojirimycin derivatives on carbohydrates in rat small intestine. Drugs Exp. Clin. Res. 13, 517-524
  12. Vichayanrat, A., Ploybutr, S., Tunlakit, M. and Watanakejorn, P. (2002) Efficacy and safety of voglibose in comparison with acarbose in type 2 diabetic patients. Diabetes Res. Clin. Pr. 55, 99-103 https://doi.org/10.1016/S0168-8227(01)00286-8
  13. Yasuda, K., Shimowada, K., Uno, M., Odaka, H., Adachi, T., Shihara, N., Suzuki, N., Tamon, A., Nagashima, K., Hosokawa, M., Tsuda, K. and Seino, Y. (2003) Long-term therapeutic effects of voglibose, a potent intestinal alpha-glucosidase inhibitor, in spontaneous diabetic GK rats. Diabetes Res. Clin. Pr. 59, 113-122 https://doi.org/10.1016/S0168-8227(02)00241-3
  14. William-Olsson, T. (1985) Carbohydrate digestion and ${\alpha}-glucosidase$inhibitors. Acta Med. Scand. 706, 5-39
  15. Campbell, L. K., Baker, D. E. and Campbell, R. K. (2000) Miglitol: assessment of its role in the treatment of patients with diabetes mellitus. Ann. Pharmacother. 34, 1291-1301 https://doi.org/10.1345/aph.19269
  16. Wood, I. S., Hunter, L. and Trayhurn, P. (2003) Expression of Class III facilitative glucose transporter genes (GLUT-10 and GLUT-12) in mouse and human adipose tissues. Biochem. Biophys. Res. Commun. 308, 43-49 https://doi.org/10.1016/S0006-291X(03)01322-6
  17. Defronzo, R. A., Bonadonna, R. C. and Ferrannini, E. (1992) Pathogenesis of NIDDM. A balanced overview. Diabetes Care 15, 318-368 https://doi.org/10.2337/diacare.15.3.318
  18. Defronzo, R. A. and Ferrannini, E. (1991) A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disesse. Diabetes Care 14, 173-194 https://doi.org/10.2337/diacare.14.3.173
  19. Rea, S. and James, D. E. (1997) Perspectives in diabetes: Moving GLUT4; The biogenesis and trafficking of GLUT4 storage vesicles. Diabetes 46, 1667-1677 https://doi.org/10.2337/diabetes.46.11.1667