Journal of the Korean Society of Food Science and Nutrition (한국식품영양과학회지)

The Korean Society of Food Science and Nutrition (한국식품영양과학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of YK-209 Mulberry Leaves on HMG-CoA Reductase and Lipid Composition of Liver in Streptozotocin-Induced Diabetic Rats

YK-209 뽕잎이 Streptozotocin 유발 당뇨쥐 간조직에서의 HMG-Coa Reductase 활성과 지질조성에 미치는 영향

  • 홍정희 (대구가톨릭대학교 식품영양학과) ;
  • 이순재 (대구가톨릭대학교 식품영양학과) ;
  • 박모라 (상주대학교 식품영양학과)
  • Published : 2002.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

This study was conducted to investigate the effects of YK-209 mulberry leaves on HMG-CoA reductase activity and lipid composition of liver in streptozotocin-induced diabetic rats. Sprague-Dawley male rats weighing 100 $\pm$ 10 B were randomly assigned as a normal group and four STZ-induced diabetic groups according to the level of dietary mulberry leaves supplement. The experimental diets were fed ad libidum, so that diabetes was experimentally induced by intravenous injection of STZ 55 mg/kg of body weight after feeding for 3 weeks. Animals were sacrificed on the 9th day of diabetic states. The levels of serum triglyceride, total-cholesterol and LDL-cholesterol in DM group were higher than mulberry leaves supplemented groups and normal group, but those of the mulberry leaves supplemented groups were significantly decreased to normal level. In contrast, the leavels of serum HDL-cholesterol in DM group was significantly reduced than that of normal group, but mulberry leaves supplemented groups were increased to normal level. Atherogenic index in DM group was higher about 3 fold than the normal group but the DM-0.1Y and DM-0.2Y groups were maintained the normal level. Contents of total lipid and triglyceride of liver in DM group were significantly lower than that of normal group, but the mulberry Leaves supplemented groups increased than that of DM group. The contents of hepatic cholesterol in DM group was 160% higher than that of normal group, but the mulberry leaves supplementation groups maintained the normal level. The activity of hepatic 3-hydroxy -3-methylglutaryl Coenzyme A (HMG-CoA) reductase in DM group was 43% lower than that of normal group, but had no significant difference between DM-0.1Y, DM-0.2Y and normal groups. In conclusion, YK-209 mulberry loaves has improving effect of the lipid metabolism in STZ-induced diabetic rats through hepatic HMG-CoA reductase activity, and the change of lipids contents in serum and liver.

본 연구는 YK-209뽕잎이 STZ유발 당뇨 간조직 중의 콜레스테롤대사에 미치는 영향을 규명하기 위해 수행되었다. 실험동물은 100$\pm$10 우의 Sprague-Dawley종 수컷을 정상군(nor-mal group)과 당뇨군으로 나누고 당뇨군은 다시 식이내 YK-209뽕잎 함량에 따라 각각 YK-209뽕잎을 공급하지 않은 당뇨군(DM group), 0.1% YK-209 뽕잎 식이군(DM-0.1Y group),0.2% YK-209 뽕잎 식이군(DM-0.2Y group) 및 0.4% YK-209 뽕잎 식이군(DM-0.4Y group)으로 나누어 자유섭식 시켰다. 3주 후 STZ으로 당뇨를 유발한 후 9일째에 희생하여 혈액 및 간장에서의 콜레스테롤대사 개선능에 대해 관찰하였다 YK-209 뽕잎중의 flavonoid 함량을 조사한 결과 rutin은 4.19 mg/g, iso-quercitrin은 2.01 mg/g, kaempferol-3-O-ru-tinose은 1.64 mg/B, 및 astragalin은 0.36 mg/g이었으며 총 flavonoid 함량은 8.19 mg/g 으로 청일 뽕잎보다 그 함량들이 높았다. 혈청중의 중성지방 함량은 정상군에 비해 DM군이 105% 높았으나 YK-209 뽕잎 공급군은 정상군 수준이었다. 총 콜레스테롤 함량과 LDL-cholesterol함량은 정 상군에 비해 DM군은 증가되었으며, YK-209뽕잎 공급군은 DM군에 비해 유의적으로 감소되었다. 반면 HDL-cholesterol 함량은 정상 군에 비해 DM군에서 감소되었으나 YK-209뽕잎 공급군은 정상군 수준이었다 동맥경화 지수(AI)는 DM군은 정상군에 비해 약 3배 정도 높았으나 UM-0.1Y군과 DM-0.2Y군은 정상군 수준이었다. 간조직 중의 총지질 함량과 중성지방함량은 정상군에 비해 DM군에서 감소되었으며 YK-209 뽕잎을 공급한 군에서 DM군에 비해 증가되었다. 간조직의 콜레스테롤 함량은 DM군에서 정상군에 비해 160%증가되었으나YK-209 뽕잎 공급군은 정상군 수준이었다. 간조직 중의 HMG-CoA reductase 활성은 정 상군에 비 해 DM군이 43% 감소되었으나 DM-0.1Y군과 DM-0.2Y군은 정상군 수준이었다. 결론적으로 YK-209 뽕잎은 STZ유발 당뇨쥐의 간조직의 HMG-CoA reductase활성의 조절 및 혈액과 간조직의 콜레스테롤 농도를 감소시키는 효과가 있음이 규명되었다.

Keywords

References

  1. Ganda OP. 1985. Pathogenesis of macrovascular disease including in the influence of lipid. In Joslins' Diabetes Mellitus. 12th ed. Lea and Febiger, Philadelphia. p 217.
  2. Sheng J, Yuji M, Kenji M, Shinji K, Tadashi N, Katsuto T, Masharu K, Seiichiro T. 1988. Increased activity of intestinal Acyl-Co A : cholesterol acyltransferase in rats with streptozotocin- induced diabetes and restoration by insulin supplement. Diabetes 37: 342-346. https://doi.org/10.2337/diabetes.37.3.342
  3. Feingold KR, Arthur M, Saleh A, Mounzer S, Carl G. 1990. Small intestinal fatty acid synthesis is increased in diabetic rats. Endocrinology 127: 2247-2252. https://doi.org/10.1210/endo-127-5-2247
  4. Francois B. 1996. Non-insulin dependent diabetes and reverse cholesterol transport. Athersclerosis 124: 39S-42S. https://doi.org/10.1016/0021-9150(96)05855-8
  5. Kim SY, Lee WC, Kim HB, Kim AJ, Kim SK. 1998. Antihyperlipidemic effects of methanol extracts from mulberry leaves in cholesterol induced hyperlipidemia in rats. J Kor Soc Food Sci Nutr 27: 1217-1222.
  6. Cha JY, Kim DJ, Cho YS. 2001. Effect of stem bark extract from cudrania tricuspidata on the concentrations of lipid and lipid peroxidation in rats fed a cholesterol diet. Kor J Life Sci 11: 328-334.
  7. Cho MR, Choue RW, Chung SH, Ryu JW. 1998. Effects of silkworm powder on blood glucose and lipid levels in NIDDM (Type II) patients. Kor J Nutr 31: 1139-1150.
  8. Li SZ. 1978. Compendium of materia medica. People's Medical Publishing House, Beijing. p 2067.
  9. Tang W, Eisenbrand G. 1992. Chinese drugs of plant origin. Springer-Verlag, Beijing. p 669-696.
  10. Courtiere A, Molard F, Reyband J. 1995. Differential effects of in vitro peroxidation on peripheral- and central-type benzodiazepine receptors. Protection by diverse antioxidants. Biochem Pharmacol 50: 1815-1822. https://doi.org/10.1016/0006-2952(95)02058-6
  11. Purusotam B, Shigetoshi K, Satoshi T, Mineo S, Tsuneo N. 1993. Two new 2-arylbenzofuran derivatives from hypoglycemic activity-bearing fractions of morus insignis. Chem Pharm Bull 41: 1238-1243. https://doi.org/10.1248/cpb.41.1238
  12. Massayasu K, Fu-jun Chen, Noboru N, Ikuho K, Naoki A, Sakuji K. 1995. Anti hyperglycemic effect of N-containing sugars delived from mulberry leaves in streptozotocin-induced diabetic mice. J Traditional Medicine 12: 214-219.
  13. Lee HS, Chung KS, Kim SY, Ryu KS, Lee WC. 1998. Effect of severa sericultural products on blood glucose lowering for alloxan-induced hyperglycemic mice. Korean J Seric Sci 40: 38-42.
  14. Sung GB. 1998. Recent mulberry research trend and direction for the improvement. Korean J Seric Sci 40: 180-184.
  15. Shin DH. 1998. Antioxidative substances in mulberry leaves. J Korean Oil Chemists Soc 16(3): 27-31.
  16. Yun SJ, Lee WC. 1994. Characteristics of superoxide dismutase of mulberry leaf. Korean J Breed 26: 389-393
  17. Yen GC, Wu SC, Duh PD. 1996. Extraction and identification of anti-oxidant components from the leaves of mulberry (Morus alba L.). J Biol Chem 261: 12879-12882.
  18. Fujimoto T, Nomura T. 1985. Components of root bark of cudrania tricuspidata 3. Isolation and structure studies on the flavonoids. Planta Med 51: 190-196. https://doi.org/10.1055/s-2007-969453
  19. Kim SH, Kim NJ, Choi JS, Park JC. 1993. Determination of flavonoids by HPLC and biological activities from the leaves of cudrania tricuspidata bureau. J Kor Soc Food Sci Nutr 22: 68-72.
  20. Chen F, Nakashima N, Kimura I, Kimura M, Asano N, Koya S. 1995. Potentiating effects on pilocarpine-induced saliva secretion by extracts and N-containing sugars derived from mulberry leaves in streptozotocin-diabetic mice. Bio Pharm Bull 18: 1676-1680. https://doi.org/10.1248/bpb.18.1676
  21. Yun SJ, Lee WC. 1995. Studies on the utilization of phamacologically active constituents in mulberry: 1. varietal and seasonal variations of flavonol glycoside content in leaves. RDA J Arig Sci 37: 201-205.
  22. Friedwald WT, Levy RI, Fedreicson DS. 1972. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without was of the preparative Ultracentrifuge. Clin Chem 18: 499-506.
  23. Fiordaliso M, Kok N, Desager JP, Goethals F, Deboyser D. Roberfoid M, Delzenne N. 1977. Dietary oligofructose lowers triglycerides, phospholipids and cholesterol in serum and very low density lipoproteins of rats. Lipids 30: 163-167. https://doi.org/10.1007/BF02538270
  24. Folch JM, Lees M, Stanley GHS. 1957. A simple method for the isolation and purification of total lipids from animal tissue. J Biol Chem 26: 497-509.
  25. Sale FD, Marchesini S, Fishman PH, Berra B. 1984. A sensitive enzymatic assay for determination of cholesterol in lipid extracts. Academic Press Inc., New York. p 347-350.
  26. Hulcher FH, Oleson WH. 1973. Simplified spectrophotometric assay for microsomal 3-hydroxy-3-methylglutaryl CoA reductase by measurement of coenzyme A. J Lipid Res 14: 625-631.
  27. Yun SJ, Lee WC. 1995. Studies on the utilization of pharmacologically active constituents in mulberry 1. Verietal and seasonal variations of flavonol glycoside content in leaves. RDA J Agri Sci 37: 201-205.
  28. Markham KR. 1989. Flavones, flavonols and their glycosides. Methods in Plant Biochemistry 1: 197-235. https://doi.org/10.1016/B978-0-12-461011-8.50012-3
  29. Kim YS, Chung SH, Suh HJ, Chung ST, Cho JS. 1994. Rutin and mineral contents on improved kinds of Korean buckwheat at growing stage. Korean J Food Sci Technol 26: 759-763.
  30. Forman S, Estilow ML, Vailenko P. 1996. STZ diabetes alters immunoreactive $\beta$-endorphin levels and pain perception after 8 wk in female rats. Diabetes 35: 1309-1313 https://doi.org/10.2337/diabetes.35.12.1309
  31. Pain VM, Garlick P. 1974. Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in tissues of the rat in vivo. J Biol Chem 249: 4510-4
  32. Sexton WS. 1994. Skeletal muscle vascular transport capacity diabetic rats. Diabetes 43: 225-231 https://doi.org/10.2337/diabetes.43.2.225
  33. Lau AL, Failla ML. 1984. Urinary excretion of zinc, copper and iron in the streptozotocin-diabetic rat. J Nutr 114: 224-223
  34. Lee JS, Son HS, Maeng YS, Chang YK, Ju JS. 1994. Effects of buckwheat on organ weight, glucose and lipid metabolism in streptozotocin induced diabetic rats. J Kor Nutr 27: 819-827.
  35. Steiner G, Chow A, Little JA. 1978. Hypertriglyceridemia associated with deficiency of apolipoprotein C-II. N Eng G Med 298: 1256-1273.
  36. Kim SY, Lee WC, Kim HB, Kim AJ, Kim SK. 1998. Antihyperlipidemic effects of methanol extracts from mulberry leaves in cholesterol induced hyperlipidemia in rats. J Kor Soc Food Sci Nutr 27: 1217-1222.
  37. Goldstein JL, Brown MS. 1997. The low-density lipoprotein pathway and its relation to atherosclerosis. Annu Rev Biochem 46: 897-930. https://doi.org/10.1146/annurev.bi.46.070177.004341
  38. Kim MH, Kim HY, Kim WK, Kim JY, Kim SH. 2001. Effects of soy oligosaccharides on blood glucose and lipid metabolism in streptozotocin-induced diabetic rats. Kor J Nutr 34: 3-13.
  39. Lim SJ, Kim YS. 1998. The effect of butanol fraction of polygonatum odoratum with vitamin E on blood glucose levels and lipid peroxidations in streptozotocin-induced diabetic rats. Kore J Nutr 31: 1385-1393.
  40. Choi JW, Sohn KH, Kim SH. 1991. The effects of nicotinamide on the serum lipid composition in streptozotocin-induced diabetic rats. J Korean Soc Food Nutr 20: 306-311
  41. O'Meara NMG, Devery RAM, Owens D, Collins PB, Johnson AH, Tomkin GH. 1990. Cholesterol metabolism in alloxaninduced diabetic rabbits. Diabetes 39: 626-633. https://doi.org/10.2337/diabetes.39.5.626
  42. Lakshmanan MR, Nepokroeff CM, Ness GC, Dugan RE, Potter JW. 1973. Stimulation of insulin of rat liver hydroxymethylglutaryl CoA reductase and cholesterol synthesizing activities. Biochem Biophys Res Commun 50: 704-10. https://doi.org/10.1016/0006-291X(73)91301-6
  43. Huber J, Guder W, Latzin S, Hamprecht B. 1973. The influence of insulin and glucagon on HMG CoA reductase activity in rat liver. Hoppe-Seylers Z Physiol Chem 354: 795-798.
  44. Bhathena SJ, Avigan J, Schreiner ME. 1974. Effect of insulin on sterol and fatty acid synthesis and hydroxy-methylglutaryl CoA reductase activity in mammalian cells grown in culture. USA Proc Natl Acad Sci 71: 2174-2178. https://doi.org/10.1073/pnas.71.6.2174
  45. Nakayama H, Nakagawa S. 1977. Influence of streptozotocin diabetes on intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in the rat. Diabetes 26: 439-444. https://doi.org/10.2337/diabetes.26.5.439
  46. Edwards PA, Lan SF, Fogelman AM. 1984. High density lipoproteins and lecithin dispersions increase the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase by increasing the rate of synthesis and decreasing the rate of degradation of the enzyme. J Biol Chem 259: 8190-8194.
  47. Choi YS, Lee SY. 1992. Serum cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A reductase. J Korean Soc Food Nutr 21: 580-593.

Cited by

  1. The Positive Effect of LuoHanGuo as  Sugar Substitute on Blood Glucose and Metabolism in Streptozotocin-Induced Diabetic Mice vol.46, pp.3, 2016, https://doi.org/10.9729/AM.2016.46.3.140
  2. Studies on a New Alimentotherapy for Diabetic Patients vol.32, pp.4, 2003, https://doi.org/10.3746/jkfn.2003.32.4.614
  3. Hepatoprotective Activity of Scutellariae Radix Extract in Mice Fed a High Fat Diet with Chronic Alcohol Exposure 2011, https://doi.org/10.1002/ptr.3370
  4. Effects of Jerusalem Artichoke (Helianthus tuberosus L.) Extracts on Blood Glucose and Lipid Metabolism in STZ-induced Diabetic Rats vol.47, pp.4, 2015, https://doi.org/10.15324/kjcls.2015.47.4.203
  5. Effects of the C3G/D3G anthocyanins-rich black soybean testa extracts on improvement of lipid profiles in STZ-induced diabetic rats vol.48, pp.4, 2015, https://doi.org/10.4163/jnh.2015.48.4.299
  6. Effects of Silkworm Extract on Disaccharidase Activities of Small Intestine and Blood Glucose-Lowering in C57BL/6J Mice vol.10, pp.1, 2002, https://doi.org/10.3746/jfn.2005.10.1.034
  7. Effects of Water Extracts from Mulberry Leaves on Hepatic HMG-CoA Reductase and Acyl-CoA-Cholesterol Acyl Transferase Activity in Rats Fed High Cholesterol Diets vol.11, pp.1, 2002, https://doi.org/10.3746/jfn.2006.11.1.042
  8. 청국장 점질성 중합체의 첨가 식이가 Streptozotocin 유발 당뇨쥐의 혈당 및 혈청지질 감소에 미치는 영향 vol.37, pp.1, 2002, https://doi.org/10.3746/jkfn.2008.37.1.35