Amelioration of Plasma Glucose and Cholesterol levels in Db/db Mice by a Mixture of Chinese Herbs

Db/db 마우스 모델에 있어서 한약재조성물의 혈당 및 혈장 콜레스테롤 개선효과

  • Lee, Jai-Heon (Dept. of Genetic Engineering, Dong-A University) ;
  • Cho, Chang-Woo (Dept. of Genetic Engineering, Dong-A University) ;
  • Han, Xiang-Fu (Dept. of Genetic Engineering, Dong-A University) ;
  • Hwang, Ji-Yeon (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University) ;
  • Kang, Min-Jung (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University) ;
  • Joo, Hee-Jeong (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University) ;
  • Kim, Mi-Eun (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University) ;
  • Seo, Yeong-Ju (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University) ;
  • Kim, Jung-In (Biohealth Product Research Center, School of Food and Life Science, Institute for Food Sciences, Inje University)
  • 이재헌 (동아대학교 생명자원과학대학 유전공학과) ;
  • 조창우 (동아대학교 생명자원과학대학 유전공학과) ;
  • 한상복 (동아대학교 생명자원과학대학 유전공학과) ;
  • 황지연 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터) ;
  • 강민정 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터) ;
  • 주희정 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터) ;
  • 김미은 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터) ;
  • 서영주 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터) ;
  • 김정인 (인제대학교 식품생명과학부, 식품과학연구소, 바이오헬스소재 연구센터)
  • Published : 2008.08.30

Abstract

Diabetes mellitus is the fifth leading cause of death among Koreans. Control of hyperglycemia and dyslipidemia is strongly correlated with decrease in risks for cardiovascular diseases, the most common and fatal diabetic complication. The effects of chronic feeding of a mixture of Chinese herbs on blood lipid profile were measured in an animal model of type 2 diabetes mellitus, db/db mice (C57BL/Ks). The Chinese herb mixture was composed of Panax ginseng C. A. Meyer,Astragalus membranaceus, Glycyrrhiza uralensis, Lycium chinense, Morus, Pueraria thunbergiana, Prunella vulgaris var. lilacina, Acanthopanax sessiliflorus, Schizandra chinensis, Scutellaria baicalensis, Dioscorea batatas, Polygonatum doratumvar. pluriflorum, Paeonia lactiflora, and Rehmannia glutinosa in a ratio of 1 : 0.7 : 0.4 : 0.7 :0.4 : 0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 :0.7 : 0.9 : 0.9. Methanol extract of the Chinese herb mixture was tested for the inhibitory activity against yeast ${\alpha}$-glucosidase in vitro. The Chinese herb mixture extract inhibited ${\alpha}$-glucosidase by 25.2% at the concentration of 0.5mg/mL. Four weekold male db/db mice (n = 14) were fed AIN-93G semipurified diet or diet containing 10% powder of the Chinese herb mixture for 6 weeks after 1 week of adaptation period. Body weight (39.5 ${\pm}$ 1.6 g) and food intake (4.3 ${\pm}$ 0.6 g/day) of the Chinese herb group were not significantly different from those of the control group (40.4 ${\pm}$ 2.6 g and 4.5 ${\pm}$ 0.6 g/day). Consumption of Chinese herb mixture significantly decreased plasma glucose level (442.5 ${\pm}$ 36.0mg/dL) compared with the control group (489.8 ${\pm}$ 34.6 mg/dL, p < 0.05). Plasma cholesterol level (159.2 ${\pm}$ 18.4 mg/dL) of the Chinese herb group was significantly lower than that of the control group (185.4 ${\pm}$ 13.7 mg/dL, p < 0.05). Blood glycated hemoglobin (6.3 ${\pm}$ 0.8%) and plasma triglyceride levels (99.4 ${\pm}$ 15.0mg/dL) of the Chinese herb group were not significantly different from those of the control group (6.7 ${\pm}$ 0.7% and 108.8 ${\pm}$ 11.0mg/dL). Thus, the Chinese herb mixture could be useful in the treatment of diabetes and cardiovascular complications of diabetes.

흰양삼, 황기, 감초, 구기자, 뽕나무잎, 갈근, 하고초, 오갈피,오미자, 황금, 산약, 황정, 작약, 생지를 1 : 0.7 : 0.4 : 0.7 : 0.4 :0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 : 0.7 : 0.9 : 0.9의 비율로 함유한 한약재 조성물의 혈당 및 지질대사 개선효과를 제2형 당뇨동물 모델인 db/db 마우스에 있어서 조사하였다. In vitro에서 한약 재조성물 메탄올 추출물의 ${\alpha}$-glucosidase 저해활성을 측정한 결과, 경구 혈당강하제로 사용중인 아카보스 (20.7%)에 비해 높은 저해활성 (25.2%)을 나타내었다. 4주령의 수컷 db/db 마우스 (C57BL/KsJ, n = 14)를 1주간의 적응기간이 지난 후 2군으로 나누어 대조군에게는 AIN-93G diet를 기본으로 한 basal diet를, 실험군에게는 동결건조된 한약재조성물 가루를 식이의 10% 수준으로 함유한 식이를 6주간 제공하였다. 한약 재조성물의 섭취는 실험동물의 체중 및 식이 섭취량에 유의적인 영향을 주지 않았으나 공복 혈당 (442.5 ${\pm}$ 36.0mg/dL)을 대조군 (489.8 ${\pm}$ 34.6mg/dL)에 비해 유의적으로 감소시켰다 (p < 0.05). 또한 한약재조성물 섭취군의 혈장 콜레스테롤 (159.2 ${\pm}$ 18.4mg/dL) 농도는 대조군 (185.4 ${\pm}$ 13.7mg/dL)에 비해 유의적으로 감소하였으며 (p < 0.05), 혈장 중성지방 농도는 한약재 조성물 섭취군 (99.4 ${\pm}$ 15.0mg/dL)이 대조군 (108.8 ${\pm}$11.0mg/dL)에 비해 낮아지는 경향을 나타내었다. 따라서 한약 재조성물의 섭취는 당뇨동물모델에 있어서 혈당 및 혈장 콜레스테롤 농도를 감소시켜, 당뇨병 개선 및 당뇨합병증 예방에 기여할 것으로 사료된다.

Keywords

References

  1. A.O.A.C. (1995) Official methods of analysis. 14th ed. Association of official analytical chemists. Washington DC, USA
  2. Centers for disease control and prevention (1999) Diabetes surveillance report. GA: US Department of Health and Human Services. Atlanta
  3. 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
  4. Fujita H, Yamagami T (2001) Fermented soybean-derived touchiextract with anti-diabetic effect via alpha-glucosidase inhibitory action in a long-term administration study with KKAy mice. Life Sci. 70:219-227 https://doi.org/10.1016/S0024-3205(01)01381-9
  5. Gonuth SM (1973) Plasma insulin and glucose profiles in normal, obese and diabetic persons. Ann. Intern. Med. 79:812-822 https://doi.org/10.7326/0003-4819-79-6-812
  6. Hanefeld M (1998) The role of acarbose in the treatment of noninsulin- dependent diabetes mellitus. J. Diabetes Complicat. 12:228-237 https://doi.org/10.1016/S1056-8727(97)00123-2
  7. Hermansen K (2001) Beneficial effects of a soy-based dietary supplement on lipid levels and cardiovascular risk markers in type 2 diabetic subjects. Diabetes Care. 24:228-233 https://doi.org/10.2337/diacare.24.2.228
  8. Hillebrand I, Boehme K, Frank G (1979) The effects of the alpha-glucosidase inhibitor BAYg5421(Acarbose) on mealstimulated elevations of circulating glucose, insulin and triglyceride levels in man. Res. Exp. Med. 175:81-86 https://doi.org/10.1007/BF01851236
  9. 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
  10. Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease. The framingum study. J.A.M.A. 241:2035-2038 https://doi.org/10.1001/jama.241.19.2035
  11. 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
  12. Koivisto VA (1993) Insulin therapy in type II diabetes. Dia-betes Care. 16:29-39 https://doi.org/10.2337/diacare.16.3.29
  13. Korea National Statistical Office (2005) The cause of death Statistics 2005. Annual report of on the cause of death statistics. Seoul, Korea
  14. Lebovitz HE (1998) $\alpha$-Glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Rev. 6:132-145
  15. Lim SJ, Kim KJ (1995) Hypoglycemic effect of Polygonatum Odoratum var. Pluriflorum Ohwi extract in streptozotocininduced diabetic rats. Korean J. Nutr. 28:727-736
  16. Lim SJ, Kim PJ (1997) Hypoglycemic and hypotensive effects of Polygonatum odoratum consumption in non-insulin dependent diabetics mellitus patients. Korean J. Soc. Food Sci. 13:47-55
  17. Meneilly GS, Ryan EA, Radziuk J (2000) Effect of acarbose on insulin sensitivity in elderly patients with diabetes. Diabetes Care. 23:1162-1167 https://doi.org/10.2337/diacare.23.8.1162
  18. Miettinen H (1998) Impact of diabetes on mortality after the first myocardial infarction. The FINMONICA myocardial infarction register study group. Diabetes Care. 21:69-75 https://doi.org/10.2337/diacare.21.1.69
  19. Mughal MA, Memon MY, Zardari MK, Tanwani RK, Ali M (2000) Effect of acarbose on glycemic control, serum lipids and lipoproteins in type 2 diabetes. J. Pak. Med. Assoc. 50:152-156
  20. Musabayane CT, Bwititi PT, Ojewole JA (2006) Effects of oral administration of some herbal extracts on food consumption and blood glucose levels in normal and streptozotocin-treated diabetic rats. Methods Find. Exp. Clin. Pharmacol. 28:223-228 https://doi.org/10.1358/mf.2006.28.4.990202
  21. Nishioka T, Kawabata J, Aoyama Y (1998) Baicalein, an alphaglucosidase inhibitor from Scutellaria baicalensis. J. Nat. Prod. 61:1413-1415 https://doi.org/10.1021/np980163p
  22. Oku T, Yamada M, Nakamura M, Sadamori N, Nakamura S (2006) Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity. Br. J. Nutr. 95:933-938 https://doi.org/10.1079/BJN20061746
  23. Park Y, Boo HO, Park YL, Cho DH, Lee HH (2007) Antioxidant activity of Momordica charantia L. extract. Korean J. Medicinal Crop Sci. 15:56-61
  24. Prosky L, Asp NG, Schweizer TF, DeVries JW, Furda I (1988) Determination of insoluble, soluble, and total dietary fiber in foods and food products: interlaboratory study. J. Assoc. Off. Anal. Chem. 71:1017-1023
  25. Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W (1995) Glucagon-like peptide 1 (7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scand. J. Gastroenterol. 30:892-896 https://doi.org/10.3109/00365529509101597
  26. Seifarth C, Bergmann J, Holst JJ, Ritzel R, Schmiegel W, Nauck MA (1998) Prolonged and enhanced secretion of glucagon-like peptide 1 (7-36 amide) after oral sucrose due to alpha-glucosidase inhibition (acarbose) in type 2 diabetic patients. Diabet. Med. 15:485-491 https://doi.org/10.1002/(SICI)1096-9136(199806)15:6<485::AID-DIA610>3.0.CO;2-Y
  27. Stamler J, Vaccaro O, Neaton JD, Wentworth D (1993) Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care. 16:434-444 https://doi.org/10.2337/diacare.16.2.434
  28. Stand E, Baumgartl HJ, Fchtenbusch 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 research group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N. Engl. J. Med. 329:977-986 https://doi.org/10.1056/NEJM199309303291401
  30. Toeller M (1994) Alpha-Glucosidase inhibitors in diabetes: efficacy in NIDDM subjects. Eur. J. Clin. Invest. 24(S). 3:31-35
  31. UK Prospective diabetes study (UKPDS) Group (1998) Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 352:837-853 https://doi.org/10.1016/S0140-6736(98)07019-6
  32. Wang BT, Cheng YH (2006) Xinbian meirong bencao. Military medicine science publishing co., China
  33. Watanabe J, Kawabata J, Kurihara H, Niki R (1997) Isolation and identification of $\alpha$-glucosidase inhibitors from Tochu-cha. Biosci. Biotechi. Biochem. 61:177-178 https://doi.org/10.1271/bbb.61.177
  34. Wright BE, Vasselli JR, Katovich MJ (1998) Positive effects of acarbose in the diabetic rat are not altered by feeding schedule. Phys. Behavior. 63:867-874 https://doi.org/10.1016/S0031-9384(98)00013-4
  35. Zavaroni I, Reaven GM (1981) Inhibition of carbohydrateinduced hypertriglyceridemia by a disaccharidase inhibitor. Metabolism. 30:417-420 https://doi.org/10.1016/0026-0495(81)90125-6