Inhibitory activity of Euonymus alatus against alpha-glucosidase in vitro and in vivo

  • Lee, Soo-Kyung (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Hwang, Ji-Yeon (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Song, Ji-Hyun (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Jo, Ja-Rim (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Kim, Myung-Jin (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Kim, Mi-Eun (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University) ;
  • Kim, Jung-In (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Institute of Biomedical Engineering, Inje University)
  • Published : 2007.09.20

Abstract

The major goal in the treatment of diabetes mellitus is to achieve near-normal glycemic control. To optimize both fasting blood glucose and postprandial glucose levels is important in keeping blood glucose levels as close to normal as possible. ${\alpha}-Glucosidase$ is the enzyme that digests dietary carbohydrate, and inhibition of this enzyme could suppress postprandial hyperglycemia. The purpose of this study was to test the inhibitory activity of methanol extract of Euonymus alatus on ${\alpha}-glucosidase$ in vitro and in vivo to evaluate its possible use as an anti-diabetic agent. Yeast ${\alpha}-glucosidase$ inhibitory activities of methanol extract of E. alatus were measured at concentrations of 0.50, 0.25, 0.10, and 0.05 mg/ml. The ability of E. alatus to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without E. alatus extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast. Plasma glucose levels were measured at 30, 60, 90, 120, 180, and 240 min. Plasma glucose levels were expressed in increments from baseline, and incremental areas under the response curve were calculated. Extract of E. alatus, which had an $IC_{50}$ value of 0.272 mg/ml, inhibited yeast ${\alpha}-glucosidase$ activity in a concentration-dependent manner. A single oral dose of E. alatus extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that E. alatus has an antihyperglycemic effect by inhibiting ${\alpha}-glucosidase$ activity in this animal model of diabetes mellitus.

Keywords

References

  1. Abrahaamson MJ (2004). Optimal glycemic control in type 2 diabetes mellitus: fasting and postprandial glucose in context. Arch Intern Med 164:486-491 https://doi.org/10.1001/archinte.164.5.486
  2. Avignon A, Radauceanu A & Monnier L (1997). Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care 20:1822-1826 https://doi.org/10.2337/diacare.20.12.1822
  3. Balflour JA & McTavish D (1993). Acarbose. An update of its pharmacology and therapeutic use in diabetes mellitus. Drugs 46: 1025-1054 https://doi.org/10.2165/00003495-199346060-00007
  4. Baron AD (1998). Postprandial hyperglycaemia and ${\alpha}-glucosidase$ inhibitors. Diabetes Res Clin Pract 40:S51-55 https://doi.org/10.1016/S0168-8227(98)00043-6
  5. Bastyr EJ, Stuart CA, Brodows RG, Schwartz S, Graf CJ, Zagar A & Robertson KE (IOEZ Study Group) (2000). Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. Diabetes Care 23:1236-1241 https://doi.org/10.2337/diacare.23.9.1236
  6. Campbell RK, White JR & Nomura D (2001). The clinical importance of postprandial hyperglycemia. Diabetes Educ 27:624-637 https://doi.org/10.1177/014572170102700504
  7. Centers for Disease Control and Prevention (1999). Diabetes Surveillance Report, Atlanta, GA: US Department of Health and Human Services
  8. Coniff RF, Shapiro JA, Robbins D, Kleinfield R, Seaton TB, Beisswenger P & McGill JB (1995). Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM. Diabetes Care 18:817-824 https://doi.org/10.2337/diacare.18.6.817
  9. Haller H (1998). The clinical importance of postprandial glucose. Diabetes Res Clin Pract 40:S43-49 https://doi.org/10.1016/S0168-8227(98)00042-4
  10. Holman RR, Cull CA & Turner RC (1999). A randomized doubleblind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care 22:960-964 https://doi.org/10.2337/diacare.22.6.960
  11. Inoue I, Takahashi K, Noji S, Awata T, Negishi K & Katayama S (1997). Acarbose controls postprandial hyper-proinsulinemia in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 36:143-151 https://doi.org/10.1016/S0168-8227(97)00045-4
  12. Jenkins DJ, Wolever TM & Jenkins AL (1988). Starchy foods and glycemic index. Diabetes Care 11:149-159 https://doi.org/10.2337/diacare.11.2.149
  13. Jermendy G (2005). Can type 2 diabetes mellitus be considered preventable? Diabetes Res Clin Pract 68:S73-S81 https://doi.org/10.1016/j.diabres.2005.03.010
  14. Joo HJ, Kang MJ, Seo TJ, Kim HA, Yoo SJ, Lee SK, Lim HJ, Byun BH & Kim JI (2006). The hypoglycemic effect of Saururus chinensis Baill in animal models of diabetes mellitus. Food Science and Biotechnology 15:413-417
  15. Kim CH, Kim DI, Kwon CN, Kang SK, Jin UH, Suh SJ, Lee TK & Lee IS (2006). Euonymus alatus (Thunb.) Sieb induces apoptosis via mitochondrial pathway as prooxidant in human uterine leiomyomal smooth muscle cells. Int J Gynecol Cancer 16: 843-848 https://doi.org/10.1111/j.1525-1438.2006.00524.x
  16. King H, Aubert RE & Herman WH (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
  17. Korea National Statistical Office (2006). The cause of death Statistics 2005. Annual Report of on the Cause of Death Statistics. Korea National Statistical Office, Seoul. Republic of Korea
  18. Lee H, Kim HK & Ha TY (1993). Antitumor effect of winged Euonymus against chemically induced and malignant cell implanted- tumors in mice. Korean Journal of Immunology 15:243-253
  19. Li Y, Wen S, Kota BP, Peng G, Li GQ, Yamahara J & Roufogalis BD (2005). Punica granatum flower extract, a potent ${\alpha}-glucosidase$ inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats. J Ethnopharmacol 99:239-244 https://doi.org/10.1016/j.jep.2005.02.030
  20. Mooradian AD & Thurman JE (1999). Drug therapy of postprandial hyperglycemia. Drugs 57:19-29
  21. Oh BY, Hwang SK, Cheong MY, Sin HS, Park BH, Lee JH & Kim S (2005). Components and biological activity of aqueous extract isolated from winged stem of Euonymus alatus. Korean Journal of Food Science and Technology 37:898-904
  22. Park SH, Ko SK & Chung SH (2005). Euonymus alatus prevents the hyperglycemia and hyperlipidemia induced by high-fat diet in ICR mice. J Ethnopharmacol 102:326-335 https://doi.org/10.1016/j.jep.2005.06.041
  23. Saito N, Sakai H, Sekihara H & Yajima Y (1998). Effect of an ${\alpha}-glucosidase$ inhibitor (voglibose), in combination with sulphonilureas, on glycaemic control in type 2 diabetes subjects. J Int Med Res 26:219-232 https://doi.org/10.1177/030006059802600501
  24. Sels JP, Huijberts MS & Wolffenbuttel BH (1999). Miglitol, a new alpha-glucosidase inhibitor. Expert Opin Pharmacother 1:149-156 https://doi.org/10.1517/14656566.1.1.149
  25. Seo KS, Lim JK, Park JH, Kim CH, Chung GY & Jeong HJ (2003). Antioxidative activity and biological properties in extracts of Euonymus alatus (Thnub.) Sieb. Korean Journal of Life Science 13:1-8 https://doi.org/10.5352/JLS.2003.13.1.001
  26. Shim YJ, Doo HK, Ahn SY, Kim YS, Seong JK, Park IS & Min BH (2003). Inhibitory effect of aqueous extract from the gall of Rhus Chinensis on alpha-glucosidase activity and postprandial blood glucose. J Ethnopharmacol 85:283-287 https://doi.org/10.1016/S0378-8741(02)00370-7
  27. Soonthornpun S, Rattarasarn C, Leelawattana R & Setasuban W (1999). Postprandial plasma glucose: a good index of glycemic control in type 2 diabetic patients having near-normal fasting glucose levels. Diabetes Res Clin Pract 46:23-27 https://doi.org/10.1016/S0168-8227(99)00061-3
  28. Stand E, Baumgartl HJ, Fuchtenbusch M & Stemplinger J (1999). Effect of acarbose on additional insulin therapy in type 2 diabetic patients with late failure of sulphonylurea therapy. Diabetes Obes Metab 1:215-220 https://doi.org/10.1046/j.1463-1326.1999.00021.x
  29. The Diabetes Control and Complications Trial (DCCT) Research Group (1993). The effect of intensive treatment of diabetes on the development and progression of long-term complications in the diabetes control in insulin-dependent diabetes mellitus. N Engl J Med 329:977-986 https://doi.org/10.1056/NEJM199309303291401
  30. UK Prospective Diabetes Study (UKPDS) Group (1998). Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ 317:703-713 https://doi.org/10.1136/bmj.317.7160.703
  31. Watanabe J, Kawabata J, Kurihara H & Niki R (1997). Isolation and identification of ${\alpha}-glucosidase$ inhibitors from Tochu-cha (Encommia ulmoides). Biosci Biotechnol Biochem 61:177-178 https://doi.org/10.1271/bbb.61.177
  32. Youn JY, Park HY & Cho KH (2004). Anti-hyperglycemic activity of Commelina communis L.: inhibition of ${\alpha}-glucosidase$. Diabetes Res Clin Pract 66S:S149-155