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The Hypoglycemic Effect of Complex of Chinese Traditional Herbs (CTH) and Macelignan in Type 2 Diabetic Animal Model

레이저 제2형 당뇨동물모델에서 macelignan과 한약제 열수 추출물의 병용효과

  • Yeo, Ji-Young (School of Korean Medicine, Pusan National University) ;
  • Cho, Soo-In (School of Korean Medicine, Pusan National University) ;
  • Jung, Myeong-Ho (School of Korean Medicine, Pusan National University)
  • 여지영 (부산대학교 한의학전문대학원) ;
  • 조수인 (부산대학교 한의학전문대학원) ;
  • 정명호 (부산대학교 한의학전문대학원)
  • Received : 2010.04.29
  • Accepted : 2010.06.21
  • Published : 2010.07.30

Abstract

This study investigated the efficacy of macelignan and hot water with Chinese traditional herb (CTH) extract on altering severe diabetic conditions in C57BL/KsJ-db/db mice. Previously, the anti-diabetic effects of macelignan were partly reported as a PPAR $\alpha/\gamma$-dual agonist. Here, we futher studied whether a combination of macelignan and CTH had more beneficial effects or not. The macelignan and CTH compound significantly decreased fasting blood glucose and HbA1c compared to macelignan-treated mice, and also significantly improved postprandial glucose, insulin sensitivity, and plasma lipid profiles (FFA, and TG). On the other hand, insulin levels were not significantly changed compared to the diabetic control group. There were no significant changes in the concentrations of total cholesterol and HDL-cholesterol, but there were changes in HTR and AI. These results suggest that the macelignan and CTH compound ameliorates hyperglycemia and efficiently improves postprandial glucose, insulin sensitivity, and hyperlipidemia compared with macelignan in db/db mice. Moreover, the macelignan and CTH compound seems to be more potent in affecting diabetic complications than macelignan.

본 연구는 macelignan과 CTH를 제2형 당뇨병동물모델에 3주간 병용 투여하여 macelignan을 단독으로 투여했을 때보다 더 나은 효과가 있는지를 살펴 보았다. Macelignan과 CTH의 병용 투여는 공복혈당과 내당능을 비롯하여 혈중 free fatty acids, HTR, 그리고 AI에서는 macelignan 단독 투여군과 비교하여 유의적으로 나타나는 큰 차이를 발견할 수는 없었다. 그러나, HbA1c, insulin 민감도, 그리고 혈중 triglyceride 함량에서는 유의적인 변화를 보이며 효과가 있는 것으로 나타났다. 따라서, macelignan의 단독 투여보다 CTH를 병용 투여하는 것이 당뇨병 합병증을 예방하거나 개선시킬 수 있는 잠재력이 있을 것으로 판단된다. 이에 보다 명확하게 검증하기 위해 혈당 및 대사조절 기전연구를 위한 further study가 진행되어야 할 것으로 사료된다.

Keywords

References

  1. American Institute of Nutrition: Report of Ad Hoc Committee on Standards for Nutritional Studies. 1980. J. Nutr. 110, 1717-1726.
  2. American Institute of Nutrition: Report of the American Institute of Nutrition ad hoc Committee on Standards for Nutritional Studies. 1977. J. Nutr. 107, 1340-1348.
  3. Coleman1, D. L. 1978. Obese and diabetes: Two mutant genes causing diabetes-obesity syndromes in mice. Diabetologia 14, 141-147 https://doi.org/10.1007/BF00429772
  4. Crapo, P. A., G. Reaven, and J. Olefsky. 1977. Postprandial plasma-glucose and -insulin responses to different complex carbohydrates. Diabetes 26, 1178-1183. https://doi.org/10.2337/diabetes.26.12.1178
  5. Doda, R. F. 1996. Diabetes mellitus in clinical chemistry, pp. 613-641, In Kaplan, L. A., J. P. Amadeo (eds.), Mosby-Year Book. St Louis, Mo.
  6. Duarte, N. L., S. Colagiuri, T. Palu, X. L. Wang, D. E. Wilcken. 2003. Obesity, Type II diabetes and the Ala54Thr polymorphism of fatty acid binding protein 2 in the Tongan population. Mol. Genet. Metab. 79, 183-188. https://doi.org/10.1016/S1096-7192(03)00088-X
  7. Faraj, M., G. Beauregard, A. Tardif, E. Loizon, A. Godbout, K. Cianflone, H. Vidal, and R. Rabasa-Lhoret. 2008. Regulation of leptin, adiponectin and acylation-stimulating protein by hyperinsulinaemia and hyperglycaemia in vivo in healthy lean young men. Diabetes Metab. 34, 334-342. https://doi.org/10.1016/j.diabet.2008.01.014
  8. Fasshauer, M. and R. Paschke. 2003. Regulation of adipocytokines and insulin resistance. Diabetologia 46, 1594-1603. https://doi.org/10.1007/s00125-003-1228-z
  9. Flyvbjerg, A., L. Denner, B. F. Schrijvers, R. G. Tilton, T. H. Mogensen, S. R. Paludan, and R. Rasch. 2004. Long-term renal effects of a neutralizing RAGE antibody in obese type 2 diabetic mice. Diabetes 53, 166-172. https://doi.org/10.2337/diabetes.53.2007.S166
  10. Friedman, J. E., Y. Sun, T. Ishizuka, C. J. Farrell, S. E. McCormack, L. M., Herron, P. Hakimi, P. Lechner, and J. S. Yun. 1997. Phosphoenolpyruvate carboxykinase (GTP) gene transcription and hyperglycemia are regulated by glucocorticoids in genetically obese db/db transgenic mice. J. Biol. Chem. 272, 31475-31481. https://doi.org/10.1074/jbc.272.50.31475
  11. Han, K. L., J. S. Choi, J. Y. Lee., J. Song, M. K. Joe., M. H. Jung, and J. K. Hwang. 2008. Therapeutic potential of peroxisome proliferators-activated receptor-alpha/gamma dual agonist with alleviation of endoplasmic reticulum stress for the treatment of diabetes. Diabetes 57, 737-745. https://doi.org/10.2337/db07-0972
  12. International Diabetes Federation. 2003. International Diabetes Federation: Diabetes Atla. pp. 17-71, 2nd eds., Belgium.
  13. Jeong, H. J., H. Y. Kwon, J. T. Han, Y. J. Kim, and A. K. Lee. 2008. Cost-effectiveness analysis of type 2 DM screening program of national health insurance corporation. Kor. J. Health Economics and Policy 14, 29-50.
  14. Jin, D. Q., C. S. Lim, J. K. Hwang, I. Ha, and J. S. Han. 2005. Anti-oxidant and anti-inflammatory activities of macelignan in murine hippocampal cell line and primary culture of rat microglial cells. Biochem. Biophys. Res. Commun. 331, 1264-1269. https://doi.org/10.1016/j.bbrc.2005.04.036
  15. Khan, B., M. S. Arayne, S. Naz, and N. Mukhtar. 2005. Hypogylcemic activity of aqueous extract of some indigenous plants. Pak. J. Pharm. Sci. 18, 62-64.
  16. Kim, K. J. and Y. N. Han. 2002. Lignans from Myristica fragrans. Yakhak Hoeji 46, 98-101.
  17. Kim, S. H., E. J. Shin, and C. K. Hyun. 2005. Enhancing effect of extracts of phellodendri cortex on glucose uptake in normal and insulin-resistant 3T3-L1 adipocytes. Kor. J. Pharmacogn. 36, 291-298.
  18. Kim, S. H., D. H. Lee, S. H. Kwon, B. H. Lim, S. H. Lee, and B. C. Min. 2007. Isolation and quantitative determination method validation of myristicin from Myristica fragrans Houttuyn. Kor. J. Pharmacogn. 38, 19-21.
  19. Klein, R., B. E. Klein, S. E. Moss, M. D. Davis, and D. L. DeMets.1988. Glycosylated hemoglobin predicts the incidence and progression of diabetic retinopathy. JAMA 260, 2864-2871. https://doi.org/10.1001/jama.260.19.2864
  20. Korea Pharmaceutical Traders Association. 2000. Korea Drug Test Laboratory Chinese medicine (herb) REGULATION. 370.
  21. Korean Diabetes Association, Health Insurance Review & Assessment Service. 2008. Report of Task Force Team for Basic Statistical Study of Korean Diabetes Mellitus: Diabetes in Korea 2007. 1st ed., Goldfishery, Seoul. Korea.
  22. Lee, J. Y., Y. B. Han, W. S. Woo, and K. H. Shin. 1990. Antioxidant activity of diarylbutanes. Kor. J. Pharmacogn. 21, 270-273.
  23. Lee, Y. M., D. K. Kim, S. H. Kim, T. Y. Shin, and H. M. Kim. 1996. Antianaphylactic activity of Poncirus trifoliata fruit extract. J. Ethnopharmacol. 54, 77-84. https://doi.org/10.1016/S0378-8741(96)01451-1
  24. Lim, J. I. 2003. Recent research trends of diabetes drug. Health Industry and Technology Trends Spring. 28-38.
  25. Medical Economics Company. 2000. PDR for herbal medicine. 984.
  26. Ministry of Health, 2009. Welfare and Family Affairs; Korea Centers for Disease Control and Prevention: The 4th national health and nutrition examination survey. Seoul, Korea Centers for Disease Control and Prevention.
  27. Moon, E. J., Y. E. Jo, T. C. Park, Y. K. Kim, S. H. Jung, H. J. Kim, D. J. Kim, Y. S. Chung, and K. W. Lee. 2008. Clinical characteristics and direct medical costs of type 2 diabetic patients. Korean Diabetes J. 32. 358-365. https://doi.org/10.4093/kdj.2008.32.4.358
  28. Park, I. B. and S. H. Baik. 2009. Epidemiologic characteristics of diabetes mellitus in Korea: current status of diabetic patients using Korean health insurance database. Korean Diabetes J. 33. 357-362. https://doi.org/10.4093/kdj.2009.33.5.357
  29. Park, S. K., M. K. Park, J. H. Suk, M. K. Kim, Y. K. Kim, I. J. Kim, Y. H. Kang, K. J, Lee, H. S. Lee, C. W. Lee, B. H. Kim, K. I. Lee, M. K. Kim, and D. K. Kim. 2009. Cause-of-Death trends for diabetes mellitus over 10 years. Korean Diabetes J. 33. 65-72. https://doi.org/10.4093/kdj.2009.33.1.65
  30. Rai, P. K., D. Jaiswal, S. Mehta, and G. Watal. 2009. Anti-hyperglycaemic potential of Psidium guajava raw fruit peel. Indian J. Med. Res. 2009. 129, 561-565.
  31. Scott, D. K., R. M. O'Doherty., J. M. Stafford., C. B. Newgard, and D. K. Granner. 1998. The repression of hormone-activated PEPCK gene expression by glucose is insulin-independent but requires glucose metabolism. J. Biol. Chem. 273, 24145-24151. https://doi.org/10.1074/jbc.273.37.24145
  32. Shafrir, E. 1992. Animal models of non-insulin-dependent diabetes. Diabetes Metab. Rev. 8, 179-208. https://doi.org/10.1002/dmr.5610080302
  33. Shokuhin, K. H. 2000. Market trend of health foods and health ingredients. Shokhin to Kaihatsu 35, 18-34.
  34. Steinmetz, A. 2003. Treatment of diabetic dyslipoproteinemia. Exp Clin Endocrinol Diabetes. 111, 239-245. https://doi.org/10.1055/s-2003-41748
  35. Stumvoll, M., B. J. Goldstein, and T. W. van Haeften. 2005. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365, 1333-1346. https://doi.org/10.1016/S0140-6736(05)61032-X
  36. Suneetha, W. J. and T. P. Krishnakantha. 2005. Cardamom extract as inhibitor of human platelet aggregation. Phytotherapy Research 19, 437-440. https://doi.org/10.1002/ptr.1681
  37. Thorens, B. Glucose sensing and the pathogenesis of obesity and type 2 diabetes. 2008. Int. J. Obes. (Lond) 32, S62-S71.
  38. Tominaga, M., H. Eguchi, H. Manaka, K. Igarashi, T. Kato, and A. Sekikawa. 1999. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetic Care 22, 920-946. https://doi.org/10.2337/diacare.22.6.920
  39. Turner, R. C., C. A. Cull, V. Frighi, and R. R. Holman. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. 1999. JAMA 281, 2005-2012. https://doi.org/10.1001/jama.281.21.2005
  40. Wagner, A. M., A. Perez, J. L. Sanchez-Quesada, J. Ordonez-Llanos. 2005. Triglyceride-to-HDL cholesterol ratio in the dyslipidemic classification of type 2 diabetes. Diabetes Care 28, 1798-1800. https://doi.org/10.2337/diacare.28.7.1798
  41. Waisundara, V. Y., M. Huang, A. Hsu, D. Huang, and B. K. Tan. 2008. Characterization of the anti-diabetic and antioxidant effects of rehmannia glutinosa in streptozotocin-induced diabetic wistar rats. Am. J. Chin. Med. 36, 1083-1104. https://doi.org/10.1142/S0192415X08006594
  42. Wild, S. and C. D. Byrne. 2004. The role of treatment to increase HDL-cholesterol and decrease triglyceride concentrations in prevention of coronary heart disease in Type 2 diabetes. Diabet Med. 21, 8-11.
  43. Woo, W. S., K. H. Shin, H. Wangner, and H. Lotter. 1987. The structure of macelignan from Myristica fragrans. Phytochemistry 26, 1542. https://doi.org/10.1016/S0031-9422(00)81858-0
  44. Yamahara, J., T. Yamada, T. Kitani, Y. Naitoh, and H. Fujimura. 1989. Antianoxic action and active constituents of evodiae fructus. Chem. Pharm. Bull. (Tokyo) 37, 1820-1822. https://doi.org/10.1248/cpb.37.1820
  45. Yamauchi, T., J. Kamon, H. Waki, Y. Terauchi, N. Kubota, K. Hara, Y. Mori, T. Ide, K. Murakami, N. Tsuboyama-Kasaoka, O. Ezaki, Y. Akanuma, O. Gavrilova, C. Vinson, M. L. Reitman, H. Kagechika, K. Shudo, M. Yoda, Y. Nakano, K. Tobe, R. Nagai, S. Kimura, M. Tomita, P. Froguel, and T. Kadowaki. 2001. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 7, 941-916. https://doi.org/10.1038/90984