황금탕이 Streptozotocin으로 유발된 당뇨병 백서의 혈당 및 당뇨병합병증에 미치는 영향

Effects of Hwanggeum-tang Aqueous Extracts on Streptozotocin-induced Rat's Diabetes and Related Complications

  • 최병현 (대구한의대학교 한의과대학 신계내과학교실) ;
  • 윤경민 (대구한의대학교 한의과대학 신계내과학교실) ;
  • 강석봉 (대구한의대학교 한의과대학 신계내과학교실)
  • Choi, Byeong-Heon (Department of Oriental Internal Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Yoon, Gyeong-Min (Department of Oriental Internal Medicine, College of Oriental Medicine, Daegu Haany University) ;
  • Kang, Seok-Bong (Department of Oriental Internal Medicine, College of Oriental Medicine, Daegu Haany University)
  • 투고 : 2011.05.18
  • 심사 : 2011.07.18
  • 발행 : 2011.08.25

초록

The object of this study was to observe the effects of Hwanggeum-tang (HGT) aqueous extracts on Streptozotocin-induced rat's diabetes and related complications. Three different dosages of HGT extracts were orally administered oncea day for 28 days from 3 weeks after Streptozotocin treatment (60 mg/kg, single intraperitoneally administered). All the rats were checked at 3 weeks after Streptozotocin treatment as follows. Changes on the body weight, blood glucose level, kidney weight, serum BUN and creatinine level, liver weight, serum AST and ALT level, serum LDL, HDL, triglyceride and total cholesterol level were observed with changes on the pancreatic MDA content and GSH content. The results were compared with a potent antioxidant silymarin 100 mg/kg in which the effects on Streptozotocin-induced diabetes and related complications were already confirmed. As results of Streptozotocin-injected diabetes and related complications, dramatical decreases on the body weight, increase of the kidney and liver weight, increase of serum BUN, creatinine, AST, ALT, LDL, triglyceride, total cholesterol level and decreases of serum HDL level were detected in streptozotocin control as compared with intact control. In addition, marked increases of pancreatic MDA content and decreases of GSH content were also detected in streptozotocin control as compared with intact control. However, these diabetes and related complications, and inhibition of antioxidant effects induced by Streptozotocin were inhibited by 28 days continuous treatment of 50, 100 and 200 mg/kg of HGT extracts in the present study. HGT have favorable effects on the diabetes and various diabetic complications. Therefore, more detail mechanism studies should be conducedin future with the efficacy tests of individual herbal composition of HGT and the screening of the biological active compounds in herbs.

키워드

참고문헌

  1. 서울대학교의과대학. 내분비학. 서울, 서울대학교출판부, pp 203-204, 2005.
  2. 대한당뇨병학회. 당뇨병학(제 3판). 서울, 고려의학, pp 1-5, 2005.
  3. Marx, J. Unravelling the causes of diabetes. Science. 296: 686-689, 2002. https://doi.org/10.1126/science.296.5568.686
  4. Tiwari, A.K., Madhusudana Rao, J. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: present status and future prospects. Current Science. 83: 30-38, 2002.
  5. Ojewole, J.A., Adewunmi, C.O. Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice. Methods Find Exp Clin Pharmacol. 25: 453-456, 2003. https://doi.org/10.1358/mf.2003.25.6.769651
  6. Latha, M., Pari, L. Effect of an aqueous extract of Scoparia dulcis on blood glucose, plasma insulin and some polyol pathway enzymes in experimental rat diabetes. Braz J Med Biol Res. 37: 577-586, 2004. https://doi.org/10.1590/S0100-879X2004000400015
  7. Ivorra, M.D., Paya, M., Villar, A. A review of natural products and plants as potential antidiabetic drugs. J Ethnopharmacol. 27: 243-275, 1989. https://doi.org/10.1016/0378-8741(89)90001-9
  8. 龔 靂. (對譯)萬病回春. 서울, 法仁文化社, p 32, 2007.
  9. 許 浚. (對譯)東醫寶鑑. 서울, 法仁文化社, p 1332, 1999.
  10. 杜鎬京. 東醫腎系學. 서울, 성보사, pp 1139-1140, 2003.
  11. nstitute of Laboratory Animal Resources(Commission on Life Sciences, National Research Council, USA). : Guide for the care and use of laboratory animals. Washington, D.C. : National Academic press. pp 1-118, 1996.
  12. Kavutcu, M., Canbolat, O., Oztürk, S., Olcay, E., Ulutepe, S., Ekinci, C., GOkhun, I.H., Durak, I. Reduced enzymatic antioxidant defense mechanism in kidney tissues from gentamicin-treated guinea pigs: effects of vitamins E and C. Nephron. 72: 269-274, 1996. https://doi.org/10.1159/000188853
  13. Lowry, O.H., Rosenbrough, N.J., Farr, A.L., Randall, R.J. Protein measurement with the Folin phenol reagent. J Biol Chem. 193: 265-275, 1951.
  14. Draper, H.H., Hadley, M. Methods in Enzymology. New York: Academic Press. p 421, 1990.
  15. Eyer, P., Podhradský, D. Evaluation of the micromethod for determination of glutathione using enzymatic cycling and Ellman's reagent. Anal Biochem. 153: 57-66, 1986. https://doi.org/10.1016/0003-2697(86)90061-8
  16. Sathishsekar, D., Subramanian, S. Beneficial effects of Momordica charantia seeds in the treatment of streptozotocin-induced diabetes in experimental rats. Biol Pharm Bull. 28: 978-983, 2005. https://doi.org/10.1248/bpb.28.978
  17. Quine, S.D., Raghu, P.S. Effects of (-)-epicatechin, a flavonoid on lipid peroxidation and antioxidants in streptozotocin-induced diabetic liver, kidney and heart. Pharmacol Rep. 57: 610-615, 2005.
  18. Wellington, K., Jarvis, B. Silymarin: a review of its clinical properties in the management of hepatic disorders. Bio Drugs. 15: 465-489, 2001.
  19. Lorenz, D., Mennicke, W.H. Elimination of drugs in cholecystectomized patients. Studies with silymarin in patients with extrahepatic complications. Methods Find Exp Clin Pharmacol. 3: 103-106, 1981.
  20. Velussi, M., Cernigoi, A.M., De Monte, A., Dapas, F., Caffau, C., Zilli, M. Long-term (12 months) treatment with an anti-oxidant drug (silymarin) is effective on hyperinsulinemia, exogenous insulin need and malondialdehyde levels in cirrhotic diabetic patients. J Hepatol. 26: 871-879, 1997. https://doi.org/10.1016/S0168-8278(97)80255-3
  21. Saller, R., Meier, R., Brignoli, R. The use of silymarin in the treatment of liver diseases. Drugs. 61: 2035-2063, 2001. https://doi.org/10.2165/00003495-200161140-00003
  22. Lirussi, F., Beccarello, A., Zanette, G., De Monte, A., Donadon, V., Velussi, M., Crepaldi, G. Silybin-beta-cyclodextrin in the treatment of patients with diabetes mellitus and alcoholic liver disease. Efficacy study of a new preparation of an anti-oxidant agent. Diabetes Nutr Metab. 15: 222-231, 2002.
  23. Huseini, H.F., Larijani, B., Heshmat, R., Fakhrzadeh, H., Radjabipour, B., Toliat, T., Raza, M. The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trial. Phytother Res. 20: 1036-1039, 2006. https://doi.org/10.1002/ptr.1988
  24. 鞠潤範, 金相贊, 朴宣東, 朴性奎, 徐富一, 徐榮培, 申舜植, 李尙仁, 李長泉, 李棣, 鄭宗佶, 朱榮丞, 崔湖榮. 方劑學. 서울, 圖書出版 永林社, pp 205-206, 2008.
  25. Guerrero-Analco, J.A., Hersch-Martinez, P., Pedraza-Chaverri, J., Navarrete, A., Mata, R. Antihyperglycemic effect of constituents from Hintonia standleyana in streptozotocin-induced diabetic rats. Planta Med. 71: 1099-1105, 2005. https://doi.org/10.1055/s-2005-873137
  26. Pinzone Fox, M.L., Sastry, M.K., Parenti, D.M., Simon, G.L. : Plasma leptin concentration increases early during highly active antiretroviral therapy for acquired immunodeficiency syndrome, independent of body weight. J Endocrinol Invest. 28: 1-3, 2005. https://doi.org/10.1007/BF03345520
  27. Cohen, M.P., Clements, R.S., Cohen, J.A., Shearman, C.W. Prevention of decline in renal function in the diabetic db/db mouse. Diabetologia. 39: 270-274, 1996. https://doi.org/10.1007/BF00418341
  28. Trachtman, H., Futterweit, S., Pine, E., Mann, J., Valderrama, E. Chronic diabetic nephropathy: role of inducible nitric oxide synthase. Pediatr Nephrol. 17: 20-29, 2002. https://doi.org/10.1007/s004670200004
  29. Montilla, P., Barcos, M., Munoz, M.C., Bujalance, I., Munoz-Castaneda, J.R., Tunez, I. Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats. J Biochem Mol Biol. 38: 539-544, 2005. https://doi.org/10.5483/BMBRep.2005.38.5.539
  30. Sato, S., Yamate, J., Hori, Y., Hatai, A., Nozawa, M., Sagai, M. Protective effect of polyphenol-containing azuki bean (Vigna angularis) seed coats on the renal cortex in streptozotocin-induced diabetic rats. J Nutr Biochem. 16: 547-553, 2005. https://doi.org/10.1016/j.jnutbio.2005.02.003
  31. Sodikoff, C.H. Laboratory profiles of small animal diseases. : A guide to laboratory diagnosis. 2nd ed., St. Louise: Mosby. pp 1-36, 1995.
  32. Imaeda, A., Kaneko, T., Aoki, T., Kondo, Y., Nakamura, N., Nagase, H., Yoshikawa, T. Antioxidative effects of fluvastatin and its metabolites against DNA damage in streptozotocin-treated mice. Food Chem Toxicol. 40: 1415-1422, 2002. https://doi.org/10.1016/S0278-6915(02)00111-4
  33. Clark, T.A., Heyliger, C.E., Edel, A.L., Goel, D.P., Pierce, G.N. Codelivery of a tea extract prevents morbidity and mortality associated with oral vanadate therapy in streptozotocin-induced diabetic rats. Metabolism. 53: 1145-1151, 2004. https://doi.org/10.1016/j.metabol.2004.03.017
  34. Yanardag, R., Ozsoy-Sacan, O., Bolkent, S., Orak, H., Karabulut-Bulan, O. Protective effects of metformin treatment on the liver injury of streptozotocin-diabetic rats. Hum Exp Toxicol. 24: 129-135, 2005. https://doi.org/10.1191/0960327104ht507oa
  35. Ducobu, J. Dyslipidaemia and diabetes mellitus. Rev Med Liege. 60: 578-585, 2005.
  36. Bhandari, U., Kanojia, R., Pillai, K.K. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol. 97: 227-230, 2005. https://doi.org/10.1016/j.jep.2004.11.011
  37. Garg, M.C., Singh, K.P., Bansal, D.D.. Effect of vitamin C supplementation on oxidative stress in experimental diabetes. Indian J Exp Biol. 35: 264-266, 1997.
  38. Collier, A., Wilson, R., Bradley, H., Thomson, J.A., Small, M. Free radical activity in type 2 diabetes. Diabet Med. 7: 27-30, 1990. https://doi.org/10.1111/j.1464-5491.1990.tb01302.x
  39. Ceriello, A., Quatraro, A., Giugliano, D. New insights on non-enzymatic glycosylation may lead to therapeutic approaches for the prevention of diabetic complications. Diabet Med. 9: 297-299, 1992. https://doi.org/10.1111/j.1464-5491.1992.tb01783.x
  40. Giugliano, D., Ceriello, A., Paolisso, G. Oxidative stress and diabetic vascular complications. Diabetes Care. 19: 257-267, 1996. https://doi.org/10.2337/diacare.19.3.257