YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Anti-diabetic Mechannism Study of Korean Red Ginseng by Transcriptomics

전사체 프로파일을 이용한 고려 홍삼의 항당뇨 기전 연구

  • Yuan, Hai-Dan (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University) ;
  • Shin, En-Jung (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University) ;
  • Chung, Sung-Hyun (Pharmacology and Clinical Pharmacy Lab., College of Pharmacy, Kyung Hee University)
  • 원해단 (경희대학교 약학대학 약물학 임상약학교실) ;
  • 신은정 (경희대학교 약학대학 약물학 임상약학교실) ;
  • 정성현 (경희대학교 약학대학 약물학 임상약학교실)
  • Published : 2008.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.

Keywords

References

  1. Ugochukwu, N. H. and Figgers, C. L. : Modulation of the flux patterns in carbohydrate metabolism in the livers of streptozoticin-induced diabetic rats by dietary caloric restriction. Pharmacol. Res. 54, 172 (2006) https://doi.org/10.1016/j.phrs.2006.04.004
  2. Cho, W. C., Chung, W. S., Lee, S. K., Leung, A. W., Cheng, C. H. and Yue, K. K. : Ginsenoside Re of Panax ginseng possesses significant antioxidant and antihyperlipidemic efficacies in streptozotocin-induced diabetic rats. Eur. J. Pharmacol. 550, 173 (2006) https://doi.org/10.1016/j.ejphar.2006.08.056
  3. 2005 당뇨병기초 통계연구 TFT (대한 당뇨병 학회, 건강보험심사평가원) 자료
  4. Kim, Y. M., Cha, B. S., Kim, D. J., Choi, S. H., Kim, S. K., Ahn, C. W., Lim, S. K., Kim, K. R., Huh, K. B. and Lee, H. C. : Predictive clinical parameters for therapeutic efficacy of rosiglitazone in Korean type 2 diabetes mellitus. Diabetes. Res. Clin. Pract. 67, 43 (2005) https://doi.org/10.1016/j.diabres.2004.05.001
  5. Zhang, B. B. and Moller, D. E. : New approaches in the treatment of type 2 diabetes. Curr. Opin. Chem. Biol. 4, 461 (2000) https://doi.org/10.1016/S1367-5931(00)00103-4
  6. Bailey, C. J. : Insulin resistance and antidiabetic drugs. Biochem. Pharmacol. 58, 1511 (1999) https://doi.org/10.1016/S0006-2952(99)00191-4
  7. Scheen, A. J. : Thiazolidinediones and liver toxicity Diabetes. Metab. 27, 305 (2001)
  8. Belcher, G., Lambert, C., Edwards, G., Urquhart, R. and Matthews, D. R. : Safety and tolerability of pioglitazone, metformin, and gliclazide in the treatment of type 2 diabetes. Diabetes Res. Clin. Pract. 70, 53 (2005) https://doi.org/10.1016/j.diabres.2005.02.011
  9. Stades, A. M., Heikens, J. T., Erkelens, D. W., Holleman, F. and Hoekstra, J. B. : Metformin and lactic acidosis: cause or coincidence? A review of case reports. J. Intern. Med. 255, 179 (2004) https://doi.org/10.1046/j.1365-2796.2003.01271.x
  10. Kobayashi, M., Iwata, M. and Haruta, T. : Clinical evaluation of pioglitazone. Nippon. Rinsho. 58, 395 (2000)
  11. Coleman, C. I., Hebert, J. H. and Reddy, P. : The effects of Panax ginseng on quality of life. J. Clin. Pharm. Ther. 28, 5 (2003) https://doi.org/10.1046/j.1365-2710.2003.00467.x
  12. Bucci, L. R. : Selected herbals and human exercise performance. Am. J. Clin. Nutr. 72, 624S (2000) https://doi.org/10.1093/ajcn/72.2.624S
  13. Tokuyama, S. and Takahashi, M. : Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants. Nippon Yakurigaku Zasshi. 117, 195 (2001) https://doi.org/10.1254/fpj.117.195
  14. Ryu, J. K., Lee, T., Kim, D. J., Park, I. S., Yoon, S. M., Lee, H. S., Song, S. U. and Suh, J. K. : Free radical-scavenging activity of Korean red ginseng for erectile dysfunction in noninsulin- dependent diabetes mellitus rats. Urology, 65, 611 (2003) https://doi.org/10.1016/j.urology.2004.10.038
  15. Shin, H. J., Kim, Y. S., Kwak, Y. S., Song, Y. B., Kim, Y. S. and Park, J. D. : Enhancement of antitumor effects of paclitaxel (taxol) in combination with red ginseng acidic polysaccharide (RGAP). Planta. Med. 70, 1033 (2004) https://doi.org/10.1055/s-2004-832643
  16. Wargovich, M. J. : Colon cancer chemoprevention with ginseng and other botanicals. J. Korean Med. Sci., 16, S81 (2001) https://doi.org/10.3346/jkms.2001.16.S.S81
  17. Sung, J., Han, K. H., Zo, J. H., Park, H. J., Kim, C. H. and Oh, B. H. : Effects of red ginseng upon vascular endothelial function in patients with essential hypertension. Am. J. Chin. Med. 28, 205 (2000) https://doi.org/10.1142/S0192415X00000258
  18. Vuksan, V., Sung, M. K., Sievenpiper, J. L., Stavro, P. M., Jenkins, A. L., Di Buono, M., Lee, K. S., Leiter, L. A., Nam, K. Y., Arnason, J. T., Choi, M. and Naeem, A. : Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr. Metab. Cardiovasc. Dis. 18, 46 (2008) https://doi.org/10.1016/j.numecd.2006.04.003
  19. Han, G. C., Ko, S. K., Sung, J. H. and Chung, S. H. : Compound K enhances insulin secretion with beneficial metabolic effects in db/db mice. J. Agric. Food. Chem. 55, 1064 (2007)
  20. Chomczynski, P. and Sacchi, N. : Single-step method of RNA isolation by acid guanidium thiocyanate-phenol chloroform extraction. Anal. Biochem. 162, 156 (1987)
  21. Stich, V. and Berlan, M. : Physiological regulation of NEFA availability: lipolysis pathway. Proc. Nutr. Soc. 63, 369 (2004)
  22. Raz, I., Eldor, R., Cernea, S. and Shafrir, E. : Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage. Diabetes Metab. Res. Rev. 21, 3 (2005) https://doi.org/10.1002/dmrr.493
  23. Wang, Y., Lam, K. S., Yau, M. H. and Xu, A. : Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem. J. 409, 623 (2008) https://doi.org/10.1042/BJ20071492
  24. Whitehead, J. P., Richards, A. A., Hickman, I. J., Macdonald, G. A. and Prins, J. B. : Adiponectin--a key adipokine in the metabolic syndrome. Diabetes. Obes. Metab. 8, 264 (2006) https://doi.org/10.1111/j.1463-1326.2005.00510.x
  25. Aguilera, C. M., Gil-Campos, M., Canete, R. and Gil, A. : Alterations in plasma and tissue lipids associated with obesity and metabolic syndrome. Clin. Sci. (Lond) 114, 183 (2008) https://doi.org/10.1042/CS20070115
  26. Scott, D. K., O'Doherty, R. M., Stafford, J. M., Newgard, C. B. and Granner, D. K. : The repression of hormone-activated PEPCK gene expression by glucose is insulin-independent but requires glucose metabolism. J. Biol. Chem. 273, 24145 (1998) https://doi.org/10.1074/jbc.273.37.24145
  27. Lochhead, P. A., Salt, I. P., Walker, K. S., Hardie, D. G. and Sutherland, C. : 5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes. 49, 896 (2000) https://doi.org/10.2337/diabetes.49.6.896
  28. Ho, H. Y., Cheng, M. L. and Chiu, D. : T.Glucose-6-phosphate dehydrogenase--from oxidative stress to cellular functions and degenerative diseases. Redox. Rep. 12, 109 (2007) https://doi.org/10.1179/135100007X200209
  29. Aoyama, H., Daitoku, H. and Fukamizu, A. : Nutrient control of phosphorylation and translocation of Foxo1 in C57BL/6 and db/ db mice. Int. J. Mol. Med. 18, 433 (2006)
  30. Ugochukwu, N. H. and Babady, N. E. : Antihyperglycemic effect of aqueous and ethanolic extracts of Gongronema latifolium leaves on glucose and glycogen metabolism in livers of normal and streptozotocin-induced diabetic rats. Life. Sci. 73, 1925 (2003) https://doi.org/10.1016/S0024-3205(03)00543-5
  31. Velasco, G., Geelen, M. J. and Guzman, M. : Control of hepatic fatty acid oxidation by 5'-AMP-activated protein kinase involves a malonyl-CoA-dependent and a malonyl-CoAindependent mechanism. Arch. Biochem. Biophys. 337, 169 (1997) https://doi.org/10.1006/abbi.1996.9784