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Effect of Artemisia iwayomogi Ethanol Extract on Hypoglycemic and Antioxidant Activities in Diabetic Rats

더위지기 추출물이 당뇨 흰쥐의 혈당과 항산화 효소 활성도에 미치는 영향

  • Han, Hye Kyoung (Dept. of Food and Nutrition, College of Natural Science, Duksung Women's University)
  • 한혜경 (덕성여자대학교 자연과학대학 식품영양학과)
  • Received : 2012.08.31
  • Accepted : 2012.10.09
  • Published : 2012.12.31

Abstract

This study was undertaken to evaluate the antihyperglycemic, antilipid peroxidative, and antioxidant effects of the ethanol extracts of Artemisia iwayomogi (Ai) in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Sprague-Dawley rats with a single intravenous injection (45 mg/kg b.w.) of STZ. The diabetic rats were then randomized to the diabetic and Ai extract therapy groups which were treated with Ai extract at doses of 1, 2, and 3 g/kg b.w./day, respectively, for 14 days. Oral administration of Ai (2 g/kg b.w.) significantly decreased their intake of food. Dosage of 2 g/kg of the extract significantly decreased blood glucose levels in the glucose level in diabetic rats after 4 day, there was no significant difference observed at 1 and 3 g/kg. A dose of 2 or 3 g/kg of the Ai extract significantly reduced plasma glucose levels in STZ-induced hyperglycemic rats at 7 days. The hypoglycemic effect of Ai at a dose of 2 g/kg was significantly more effective than that of STZ-control. The effect was more pronounced in 2 g/kg than 1 g and 3 g/kg. A significant reduction in triglycerides (TG) and free fatty acids (FFA), and a significant increase in liver glycogen were observed in treated diabetic rats at doses of 2 g/kg after 14 days of treatment. Administration of Ai extracts to diabetic rats showed a significant decrease in liver malondialdehyde (MDA) levels. The activity of superoxide dismutase (SOD) was significantly increased in the 3 g extract-supplemented groups. The activities of glutathione peroxidase (GSH-px) and catalase (CAT) were significantly increased in the 1 g and 3 g extract-supplemented groups. Ai extract significantly increased glutathione-S transferase (GST) activity in a dose-dependent manner compared with treatment in STZ-control rats. Our result supports the fact that the administration of Ai extract is able to reduce hyperglycemia and hyperlipidemia risk, and also reduce the oxidative stress in diabetic rats.

더위지기 추출물이 STZ으로 유발된 당뇨쥐에서 혈당, 지질 및 항산화효소에 미치는 영향을 알아보고자 용량(1 g, 2 g 및 3 g/kg b.w.)을 달리하여 14일간 경구투여한 실험에서 다음과 같은 결과를 얻었다. 정상군을 비롯한 당뇨유발군, 당뇨유발에 더위지기를 투여시킨 군을 14일간 실험한 결과 STZ 투여로 식이섭취량은 증가된 반면 체중은 감소되었는데, 더위지기 추출물을 2 g 투여 시 체중증가량의 변화는 관찰되지 않은 반면 식이섭취량은 억제되었다. 장기의 상대적인 중량비교에서 신장의 경우 당뇨대조군에 비해 더위지기 추출물을 1 g 투여 시 비대가 유의적으로 억제되었다. 당뇨로 인하여 증가된 ALT 활성도는 더위지기 추출물을 2 g과 3 g 투여 시, AST 활성도는 1 g과 3 g 투여 시 당뇨대조군에 비해 유의적으로 감소되었다. 혈장 포도당 함량은 실험 4일째부터 실험 14일째까지 당뇨대조군에 비해 더위지기 추출물을 2 g 투여함으로써 혈당치가 저하됨을 관찰할 수가 있었으며, 간의 글리코겐 함량도 더위지기 추출물을 2 g 투여 시 유의적으로 증가하였다. 혈장의 중성지방과 유리지방산 함량은 더위지기 추출물 2 g 투여 시 당뇨대조군에 비해 유의적으로 감소하였다. 동맥경화지수는 더위지기 추출물을 투여한 모든 당뇨실험군에서 유의적으로 저하되는 것으로 나타났다. 간의 MDA 함량이 모든 Ai투여군에서 당뇨대조군보다 유의적으로 감소하였다. 간에서의 항산화 효소 중 SOD 활성도는 당뇨대조군에 비해 더위지기 추출물을 3 g 투여 시 유의적으로 증가하였다. CAT와 GSH-px 활성도는 당뇨대조군에 비해 더위지기 추출물을 1 g과 3 g 투여 시 유의적으로 증가하였다. GST 활성도는 당뇨대조군에 비해 모든 Ai투여군이 유의적으로 높았으며 용량의존적으로 차이를 보였다. 이상의 실험결과를 통해 더위지기 추출물은 당뇨로 인한 체중저하를 방지하고, STZ로 유도한 고혈당을 완화시키는 항당뇨작용과 더불어 항산화효소의 활성도를 증가시켜 산화스트레스 감소를 유도하여 고혈당에 의한 조직손상을 감소시켜 주는 것으로 사료된다.

Keywords

References

  1. Kim DJ. 2011. The epidemiology of diabetes in Korea. Diabetes Metab J 35: 303-308. https://doi.org/10.4093/kdj.2010.34.1.10
  2. Korean Diabetes Association. 2007. Diabetes in Korea 2007. Report of task force team for basic statistical study of Korean diabetes mellitus. Korean Diabetes Association, Seoul, Korea.
  3. Coppey LJ, Gellett JS, Davidson EP, Dunlap JA, Lund DD, Yorek MA. 2001. Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes 50: 1927-1937. https://doi.org/10.2337/diabetes.50.8.1927
  4. Yang JA, Kim SO, Choi JH, Kwag OG, Rhee SJ, Chang HW. 1998. Activities of phospholipase $A_2$ and cyclooxygenase, and syntheses of thromboxane and pyrostacyclin in streptozotocin induced diabetic rats. J Korean Soc Food Sci Nutr 27: 175-181.
  5. Satoh K. 1978. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 90: 37-43. https://doi.org/10.1016/0009-8981(78)90081-5
  6. Han HK, Yoon SJ, Kim GH. 2009. Effects of Compositae plants on plasma glucose and lipid level in streptozotocin induced diabetic rats. J Korean Soc Food Sci Nutr 38: 674-682. https://doi.org/10.3746/jkfn.2009.38.6.674
  7. Han HK, Je HS, Kim GH. 2010. Effects of Cirsium japonicum powder on plasma glucose and lipid level in streptozotocin induced diabetic rats. Korean J Food Sci Technol 42: 343-349.
  8. Park SK, Chung BH, Kim HS, Cho YG. 2005. Classification of Artemisia spp. collections based on morphological characters and RAPD analysis. Korean J Med Crop Sci 13: 278-286.
  9. Nam SM, Ham SS, Oh DH, Kang IJ, Lee SY, Chung CK. 1998. Effects of Artemisia iwayomogi Kitamura ethanol extract on lowering serum and liver lipids in rats. J Korean Soc Food Sci Nutr 27: 338-343.
  10. Park EJ, Nan JX, Kim JY, Kang HC, Choi JH, Lee SJ, Lee BH, Kim SJ, Lee JH, Kim YC, Sohn DH. 2000. The ethanolsoluble part of a hot-water extract from Artemisia iwayomogi inhibits liver fibrosis induced by carbon tetrachloride in rats. J Pharm Pharmacol 52: 875-881. https://doi.org/10.1211/0022357001774561
  11. Song YE, Ryu JS, Chung JR, Kwak JS, Kim DH, Kim BS, Rim CW. 2001. Study on the biological activity of Artemisia iwayomogi Kitamura. Korean J Med Crop Sci 9: 116-123.
  12. Lee JA, Sung HN, Jeon CH, Gill BC, Oh GS, Youn HJ, Park JH. 2008. A carbohydrate fraction, AIP1 from Artemisia iwayomogi suppresses pulmonary eosinophilia and Th2- type cytokine production in an ovalbumin-induced allergic asthma. Down-regulation of TNF-${\alpha}$ expression in the lung. Int Immunopharmacol 8: 117-125. https://doi.org/10.1016/j.intimp.2007.10.022
  13. Seo KS, Yun KW. 2008. Antioxidant activities of extracts from Artemisia capillaris Thunb. and Artemisia iwayomogi Kitam. used as Injin. Korean J Plant Res 21: 292-298.
  14. Hwang TE. 2009. Changes in antioxidant activity during growth of Artemisia iwayomogi. Korean J Med Crop Sci 17: 286-292.
  15. Ahn BY, Jung MY, Choi DS. 2009. Protective activities of fractions of water extract obtained from Artemisia iwayomogi Kitamura against oxidative stress-induced mutagenesity: correlation with their reactive oxygen scavenging activity. Food Sci Biotechnol 18: 849-854.
  16. Reeves PG. 1997. Component of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127: 838S-841S. https://doi.org/10.1093/jn/127.5.838S
  17. Lee SS, Kim JW. 1999. Pharmacological studies on the water extract of fractions of Lycium chinese Mill. Duksung Bull Pharm Sci 2: 29-41.
  18. Bauer JD. 1982. Clinical laboratory methods. 9th ed. Ladig D, ed. Mosby Co., St. Louis, MO, USA. p 188-189.
  19. Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 28: 56-63. https://doi.org/10.1093/ajcp/28.1.56
  20. Hassid WZ, Abraham X. 1957. Chemical procedures for analysis of polysaccharides. In Method in Enzymology. Academic press, New York, NY, USA. Vol 3, p 34-50.
  21. Mihara M, Uchiyama M. 1978. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 86: 271-278. https://doi.org/10.1016/0003-2697(78)90342-1
  22. Marklund S, Marklund G. 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47: 469-474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x
  23. Aebi H. 1984. Catalase in vitro. Methods Enzymol 105: 121-126. https://doi.org/10.1016/S0076-6879(84)05016-3
  24. Lawrence RA, Burk RF. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71: 952-958. https://doi.org/10.1016/0006-291X(76)90747-6
  25. Mavis RD, Stellwagen E. 1968. Purification and subunit structure of glutathione reductase from bakers' yeast. J Biol Chem 243: 809-814.
  26. Habig WH, Pabst MJ, Jakoby WB. 1974. Glutathione Stransferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249: 7130-7139.
  27. Bergmeyer HU, Gawehn K, Grassl M. 1974. Methods of Enzymatic Analysis. 2nd ed. Bergmeter HU, ed. Academic Press Inc., New York, NY, USA. Vol 1. p 521-522.
  28. Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ. 1951. Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265-275.
  29. Hakim ZS, Patel BK, Goyal RK. 1997. Effects of chronic ramipril treatment in streptozotocin-induced diabetic rats. Indian J Physiol Pharmacol 41: 353-360.
  30. Rajkumar L, Srinivasan N, Balasubramanian K, Govindarajulu P. 1991. Increased degradation of dermal collagen in diabetic rats. Indian J Exp Biol 29: 1081-1083.
  31. Malabu UH, Dryden S, McCarthy HD, Kilpatrick A, Williams G. 1994. Effects of chronic vanadate administration in the STZ-induced diabetic rats. The antihyperglycemic action of vanadate is attributable entirely to its suppression of feeding. Diabetes 43: 9-15. https://doi.org/10.2337/diabetes.43.1.9
  32. 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. Korean J Nutr 27: 819-827.
  33. Dai S, Thompson KH, McNeill JH. 1994. One-year treatment of streptozotocin-induced diabetic rats with vanadyl sulphate. Pharmacol Toxicol 74: 101-109. https://doi.org/10.1111/j.1600-0773.1994.tb01083.x
  34. Choi SH, Park JR. 2010. Lipid modulatory functions of cysteine compounds found in genus Allium plants in diabetic mice. Korean J Food & Nutr 23: 361-367.
  35. Seyer-Hansen K. 1977. Renal hypertrophy in experimental diabetes: relation to severity of diabetes. Diabetologia 13: 141-143. https://doi.org/10.1007/BF00745142
  36. Steer KA, Sochor M, McLean P. 1985. Renal hypertrophy in experimental diabetes. Changes in pentose phosphate pathway activity. Diabetes 34: 485-490. https://doi.org/10.2337/diabetes.34.5.485
  37. Kim HS, Seong JH, Lee YG, Xie CL, Shin JM, Yoon HD. 2010. Improvements caused by silk sericin extract derived from silkworm in blood glucose and lipid concentration in diabetic rats. Korean J Food & Nutr 23: 392-398.
  38. Harvey JN, Jaffa AA, Margolius HS, Mayfield RK. 1990. Renal kallikrein and hemodynamic abnormalities of diabetic kidney. Diabetes 39: 299-304. https://doi.org/10.2337/diabetes.39.3.299
  39. Matkovics B, Kotorman M, Varga IS, Hai DQ, Varga C. 1998. Oxidative stress in experimental diabetes induced by streptozotocin. Acta Physiol Hung 85: 29-38.
  40. Kahn CR. 1985. The molecular mechanism of insulin action. Annu Rev Med 36: 429-451. https://doi.org/10.1146/annurev.me.36.020185.002241
  41. Reddi AS, Bollineni JS. 2001. Selenium-deficient diet induces renal oxidative stress and injury via TGF-${\beta}1$ in normal and diabetic rats. Kidney Int 59: 1342-1353. https://doi.org/10.1046/j.1523-1755.2001.0590041342.x
  42. Golden S, Wals PA, Okajima F, Katz J. 1979. Glycogen synthesis by hepatocytes from diabetic rats. Biochem J 182: 727-734. https://doi.org/10.1042/bj1820727
  43. Grover JK, Vats V, Yadav S. 2002. Effect of feeding aqueous extract of Pterocarpus marsupium on glycogen content of tissues and the key enzymes of carbohydrate metabolism. Mol Cell Biochem 241: 53-59. https://doi.org/10.1023/A:1020870526014
  44. Pandit R, Phadke A, Jagtap A. 2010. Antidiabetic effect of Ficus religiosa extract in streptozotocin-induced diabetic rats. J Ethnopharmacol 128: 462-466. https://doi.org/10.1016/j.jep.2010.01.025
  45. O'Meara NM, Devery RA, Owens D, Collins PB, Johnson AH, Tomkin GH. 1990. Cholesterol metabolism in alloxaninduced diabetic rabbit. Diabetes 39: 626-633. https://doi.org/10.2337/diabetes.39.5.626
  46. Kim SH, Kang JS, Lee SJ, Chung YJ. 2008. Antidiabetic effect of Korean red ginseng by puffing process in streptozotocin- induced diabetic rats. J Korean Soc Food Sci Nutr 37: 701-707. https://doi.org/10.3746/jkfn.2008.37.6.701
  47. Siegel RD, Cupples A, Schaefer EJ, Wilson PW. 1996. Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham offspring study. Metabolism 45: 1267-1272. https://doi.org/10.1016/S0026-0495(96)90246-2
  48. Boden G. 1997. Role of fatty acids in pathogenesis of insulin resistance and NIDDM. Diabetes 46: 3-10. https://doi.org/10.2337/diabetes.46.1.3
  49. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95: 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  50. Kannel WB, McGee DL. 1979. Diabetes and cardiovascular disease. The Framingham study. JAMA 241: 2035-2038. https://doi.org/10.1001/jama.1979.03290450033020
  51. Memişoğullari R, Bakan E. 2004. Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. J Diabetes Complications 18: 193-197. https://doi.org/10.1016/S1056-8727(03)00032-1
  52. Arulselvan P, Subramanian SP. 2007. Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic ${\beta}$-cells in experimental diabetes in rats. Chem Biol Interact 165: 155-164. https://doi.org/10.1016/j.cbi.2006.10.014
  53. Chow CK. 1979. Nutritional influence on cellular antioxidant defense systems. Am J Clin Nutr 32: 1066-1081. https://doi.org/10.1093/ajcn/32.5.1066
  54. Halliwell B, Gutteridge MC. 1985. Free radicals in biology and medicine. Oxford University Press, Oxford, UK. p 166-170.
  55. Searle AJ, Wilson RL. 1980. Glutathione peroxidase: effect of superoxide, hydroxyl and bromine free radicals on enzyme activity. Int J Radiat Biol Relat Stud Phys Chem Med 37: 213-217. https://doi.org/10.1080/09553008014550261
  56. Yan H, Harding JJ. 1997. Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase. Biochem J 328: 599-605. https://doi.org/10.1042/bj3280599
  57. Kesavulu MM, Giri R, Kameswara Rao B, Apparao C. 2000. Lipid peroxidation and antioxidant enzyme levels in type 2 diabetics with microvascular complications. Diabetes Metab 26: 387-392.
  58. Saravanan G, Ponmurugan P. 2011. Ameliorative potential of S-allyl cysteine on oxidative stress in STZ induced diabetic rats. Chem Biol Interact 189: 100-106. https://doi.org/10.1016/j.cbi.2010.10.001
  59. Jakoby WB. 1978. The glutathione S-transferases: a group of multifunctional detoxification proteins. Adv Enzymol Relat Areas Mol Biol 46: 383-414.
  60. Ulusu NN, Sahilli M, Avci A, Canbolat O, Ozansoy G, Ari N, Bali M, Stefek M, Stolc S, Gajdosik A, Karasu C. 2003. Pentose phosphate pathway, glutathione-dependent enzymes and antioxidant defence during oxidative stress in diabetic rodent brain and peripheral organs: effects of stobadine and vitamin E. Neurochem Res 28: 815-823. https://doi.org/10.1023/A:1023202805255
  61. Singh K, Pushpa A. 2005. Alterations in some antioxidant enzymes in cardiac tissue upon monosodium glutamate (MSG) administration to adult male mice. Indian J Clin Biochem 20: 43-46.
  62. Urano S, Hoshi-Hashizume M, Tochigi N, Matsuo M, Shiraki M, Ito H. 1991. Vitamin E and the susceptibility of erythrocytes and reconstituted liposome to oxidative stress in aged diabetics. Lipids 26: 58-61. https://doi.org/10.1007/BF02544025

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