Effects of Herbal Complex on Blood Glucose in Streptozotocin-induced Diabetic Rats and in Mice Model of Metabolic Syndrome

생약복합제의 Streptozotocin 유발 당뇨 및 대사성증후군 모델 동물에서의 혈당에 미치는 효과

  • Published : 2009.09.30

Abstract

This study was carried out to investigate the in vivo and in vitro inhibitory effect of a traditional herbal complex (HC) extract prepared from a mixture of four oriental herbs (Dioscorea Rhizoma, Glycine soja Sieb. et Zucc, Bombycis corpus, Fermented Glycine soja) that have been widely used for the treatment and prevention of diabetes mellitus on hyperglycemia. The water extract of HC showed potent inhibitory effect on $\alpha$-glucosidase with $IC_{50}$ value of 1.24 mg/mL. Additionally, the ethanol extract of HC was also found to exhibit significant inhibitory effect against protein tyrosine phosphatase $1{\beta}$ ($PTP1{\beta}$), which is known as a major regulator of both insulin and leptin signaling. In the $PTP1{\beta}$ inhibitory assay, the most active n-hexane fraction obtained from the ethanol extract of HC, was identified as a mixture of fatty acid derivatives by gas chromatography-mass spectrometry (GC-MS). In high-fat diet-low dose streptozotocin (STZ)-induced diabetic rat, the water extract of HC improved the oral glucose intolerance as compared with rosiglitazone. HC also caused a marked decrease of body weight and fasting blood glucose and a significant improvement on glucose tolerance in metabolic syndrome mice model. These findings support that this traditional HC may be useful in the control of blood glucose in diabetes mellitus and metabolic syndrome.

당뇨병 치료 및 예방에 전통적으로 사용되어온 생약 및 식품 소재로 구성된 생약복합제인 백강잠, 산약, 쥐눈이콩, 청국장가루의 복합물을 대상으로 실험관 및 동물실험을 통하여 혈당강하 효과를 확인하였다. 생약복합제 $H_2O$추출물은 당흡수에 관여하는 $\alpha$-glucosidase효소를 비교약물인 acarbose ($IC_{50}$=0.39 mg/mL)과 비교하여 1/3배 정도의 활성을 보였으며 ($IC_{50}$=1.24 mg/mL), ethanol추출물은 인슐린 내성에 관여하는 $PTP1{\beta}$ 효소작용을 ($IC_{50}=498.46{\mu}g$/mL) 효과적으로 억제하였다. $PTP1{\beta}$ 효소를 억제하는 n-hexane 분획을 대상으로 하여 GC-MS로 성분 분석한 결과 지방산유도체인 것으로 나타났다. 고지방식이와 저용량 STZ (35 mg/kg)으로 유발시킨 당뇨모델에서 OGTT 실험결과 비교약물인 rosiglitazone(당부하 30분 후 평균 60 mg/dL 의 감소)과 생약복합제 투여군의 경구 당부하능 개선효과를(당부하 30분 후 평균 30 mg/dL의 감소) 확인하였다. 또한, 대사성 증후군 모델에서는 체중증가의 감소 효과와 공복혈당의 증가를 현저히 억제함을 확인하였으며, OGTT에서도 후반부에 현저한 경구당부하능 개선 효과를 관찰 할 수 있었다. 이 결과를 바탕으로 산약, 백강잠, 쥐눈이콩, 청국장으로 조제한 생약복합제는 당뇨 및 대사성 증후군의 혈당을 조절하는 데 도움을 줄 수 있을 것이라 판단된다.

Keywords

References

  1. 통계청 (2008) 2007년 사망 및 사망원인통계결과. 8-9
  2. American Diabetes Association. (2001) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 26: s5-s20
  3. Cavaghan, M. K., Ehrmann, D. A. and Polonsky, K. S. (2000) Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J. Clin. Invest. 106: 329-333 https://doi.org/10.1172/JCI10761
  4. Inzucchi, S. E. (2002) Oral hypoglycemic therapy for type 2 diabetes. J. Am. Med. Assoc. 287: 360-372 https://doi.org/10.1001/jama.287.3.360
  5. 박종희, 이정규. (2000) 상용약용식물도감, 신일상사, 106
  6. Choi, E. M., Koo, S. J. and Hwang, J. K. (2004) Immune cell stimulating activity of mucopolysaccharide isolated from yam (Discorea batatas). J. Ethnopharmacol. 91: 1-6 https://doi.org/10.1016/j.jep.2003.11.006
  7. Kim, M. J., Kim, H. N., Kang, K. S., Baek, N. I., Kim, D. K., Kim, Y, S., Kim, S. H. and Jean, B. J. (2004) Methanol extract of Dioscorea Rhizoma inhibits pro-inflammatory cytokines and mediators in the synoviocytes of rheumatoid arthritis. Intern. Immunopharmacol. 4: 1489-1497 https://doi.org/10.1016/j.intimp.2004.07.001
  8. Hu, K. and Yao, X. (2003) The cytotoxicity of methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787), two steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca, against human cancer cells in vitro. Phytother. Res. 17: 620-626 https://doi.org/10.1002/ptr.1211
  9. Hou, W. C., Lee, M. H., Chen, H. J., Liang, W. L., Han, C. H., Liu, Y. W. and Lin, Y. H. (2001) Antioxidant activities of dioscorins, the storage protein of yam (Dioscorea batatas Decne). J. Agric. Food. Chem. 49: 4956-4960 https://doi.org/10.1021/jf010606m
  10. McAnuff, M. A., Harding, W. W., Omoruyi, F. O., Jacobs, H., Morrison, E. Y. and Asemota, H. N. (2005) Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem. Toxicol. 43:1667-1672 https://doi.org/10.1016/j.fct.2005.05.008
  11. Kwon, C. S., Sohn, H. Y., Kim, S. H., Kim, J. H., Son, K. H., Lee, J. S., Lim, J. K. and Kim, J. S. (2003) Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Biosci. Biotechnol. Biochem. 67: 1451-1456 https://doi.org/10.1271/bbb.67.1451
  12. Chen, H. L., Wang, C. H., Chang, C. T. and Wang, T. C. (2003) Effects of Taiwanese yam (Dioscorea japonica Thunb va. Pseudojaponica Yamamoto) on upper gut function and lipid metabolism in Balb/c mice. Nutrition. 19: 646-651 https://doi.org/10.1016/S0899-9007(03)00058-3
  13. Pharmacopoeia Commission of the Ministry of Public Health, P.R. China. (1995) A coloured atlas of the Chinese material medica specified in pharmacopoeia of the people's republic of China. Guangdong science & technology press. 482
  14. Abrams, J. J., Ginberg, H. and Grundy, S. M. (1982) Metabolism of cholesterol and plasma triglycerides in non-ketotic diabetes mellitus. Diabetes. 31: 903-910 https://doi.org/10.2337/diabetes.31.10.903
  15. Sa, J. H., Shin, I. C., Jeong, K. J. and Shin T. H. (2003) Antioxidative activity and chemical characteristics from different organs of small black soybean (Yak-Kong) grown in the area of Jungsun. Korean J. food Sci. Technol. 35: 309-315
  16. Yoon, K. D., Kwon, D. J., Hong, S. S., Kim, S. I. and Chung, K. S. (1996) Inhibitory effect of soybean and fermented soybean products on the chemically induced mutagenesis. J. Microbiol. Biotechnol. 24: 525-528
  17. Chung, K. S., Yoon, K. D., Dwon, D. J., Hong S. S. and Choi, S. Y. (1997) Cytotoxicity testing of fermented soybean products with various tumour cells using MTT Assay. J. Microbiol. Biotechnol. 25: 477-482
  18. Kil, J. O., Kim, G. N. and Park, I. S. (1998) Production and characterization of fibrinolytic enzyme: Optimal condition for production of the enzyme from Bacillus sp. KP - 6408 isolated from Chungkook - jang. J. Korean Soc. Food Sci. Nutr. 27: 51-56
  19. Im, C. M., Kwon, S. H., Bae, M. S., Jung, K. O., Moon, S. H. and Park, K. Y. (2006) Characteristics and increased antimutagenic effect of black soybean (Var. Seoritae) chungkukjang. Cancer Prev. Res. 11: 218-224
  20. Kim, Y. M., Jeong, Y. K., Wang,, M. H., Lee, W. Y. and Rhee, H. I. (2005) Inhibitory effect of pine extract on α-glucosidase activity and postprandial hyperglycemia. Nutrition. 21: 756-761 https://doi.org/10.1016/j.nut.2004.10.014
  21. Godbout, A. and Chiasson, J. L. (2007) Who should benefit from the use of alpha-glucosidase inhibitors? Curr. Diab. Rep. 7: 333-339 https://doi.org/10.1007/s11892-007-0055-x
  22. Matsui, T., Ogunwande, I. A., Abesundara, K. J. and Matsumoto, K. (2006) Anti-hyperglycemic Potential of natural products. Mini. Rev. Med. Chem. 6: 349-356 https://doi.org/10.2174/138955706776073484
  23. Pain, V. M. and Garlick, P. J. (1974) Effect of streptozotocin diabetes and insulin treatment on the rate of protein synthesis in issues of the rat in vivo. J. Biol. Chem. 249: 4510-4514
  24. Miyazaki, Y. l., Glass L., Triplitt, C., Matsuda, M., Cusi, K., Mahankali, A., Mahankali, S., Mandarino, L. J. and DeFronzo, R. A. (2001) Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia. 44: 2210-2219 https://doi.org/10.1007/s001250100031
  25. Defronzo, R. A. (1981) The effect of insulin on renal sodium metabolism. Diabetologia. 21: 165-171
  26. Young, I. R. and Stout, R. W. (1987) Effects of insulin and glucose on the cells of the arterial wall: Interaction of insulin with dibutyryl cyclic AMP and low density lipoprotein in arterial cells. Diabetes Metab. 13: 301-306