Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Increase in Insulin Secretion Induced by Panax ginseng Berry Extracts Contributes to the Amelioration of Hyperglycemia in Streptozotocin-induced Diabetic Mice

  • Park, Eun-Young (Laboratory of Beta Cell Biology and Autoimmunity, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Kim, Ha-Jung (Laboratory of Cell Metabolism and Gene Expression, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Kim, Yong-Kyoung (Division of Plant Science and Resources, Chungnam National University) ;
  • Park, Sang-Un (Division of Plant Science and Resources, Chungnam National University) ;
  • Choi, Jae-Eul (Division of Plant Science and Resources, Chungnam National University) ;
  • Cha, Ji-Young (Laboratory of Cell Metabolism and Gene Expression, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science) ;
  • Jun, Hee-Sook (Laboratory of Beta Cell Biology and Autoimmunity, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science)
  • Received : 2011.10.19
  • Accepted : 2012.01.17
  • Published : 2012.04.15
Download PDF
⟨ Previous Next ⟩

Abstract

Panax ginseng has long been used as a traditional herbal medicine. More recently, it has received attention for its anti-diabetic and anti-obesity effects in humans and in animal models of type 2 diabetes. In the present study, we tested the hypoglycemic effects of ginseng berry extract in beta-cell-deficient mice and investigated the mechanisms involved. Red (ripe) and green (unripe) berry extracts were prepared and administered orally (100 or 200 mg/kg body weight) to streptozotocin-induced diabetic mice daily for 10 wk. The body weight was measured daily, and the nonfasting blood glucose levels were measured after 5 and 10 wk after administration. Glucose tolerance tests were performed, and the serum insulin levels were measured. The proliferation of beta-cells was measured in vitro. The administration of red or green ginseng berry extract significantly reduced the blood glucose levels and improved the glucose tolerance in beta-cell deficient mice, with the higher doses resulting in better effects. Glucose-stimulated insulin secretion was significantly increased in berry extract-treated mice compared with streptozotocin-induced diabetic control mice. Treatment with ginseng berry extract increased beta-cell proliferation in vitro. Both red berry and green berry extracts improved glycemic control in streptozotocin-induced diabetic mice and increased insulin secretion, possibly due to increased beta-cell proliferation. These results suggest that ginseng berry extracts might have beneficial effects on beta-cell regeneration.

Keywords

References

  1. Ritzel RA. Therapeutic approaches based on beta-cell mass preservation and/or regeneration. Front Biosci 2009;14:1835-1850.
  2. Yoon JW, Jun HS. Autoimmune destruction of pancreatic beta cells. Am J Ther 2005;12:580-591. https://doi.org/10.1097/01.mjt.0000178767.67857.63
  3. Wajchenberg BL. Beta-cell failure in diabetes and preservation by clinical treatment. Endocr Rev 2007;28:187-218. https://doi.org/10.1210/10.1210/er.2006-0038
  4. Cheng Y, Shen LH, Zhang JT. Anti-amnestic and anti-aging effects of ginsenoside $Rg_1$ and $Rb_1$ and its mechanism of action. Acta Pharmacol Sin 2005;26:143-149. https://doi.org/10.1111/j.1745-7254.2005.00034.x
  5. Choo MK, Park EK, Han MJ, Kim DH. Antiallergic activity of ginseng and its ginsenosides. Planta Med 2003;69:518-522. https://doi.org/10.1055/s-2003-40653
  6. Jeong HJ, Koo HN, Myung NI, Shin MK, Kim JW, Kim DK, Kim KS, Kim HM, Lee YM. Inhibitory effects of mast cell-mediated allergic reactions by cell cultured Siberian ginseng. Immunopharmacol Immunotoxicol 2001;23:107-117. https://doi.org/10.1081/IPH-100102572
  7. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  8. Kimura M, Waki I, Chujo T, Kikuchi T, Hiyama C, Yamazaki K, Tanaka O. Effects of hypoglycemic components in ginseng radix on blood insulin level in alloxan diabetic mice and on insulin release from perfused rat pancreas. J Pharmacobiodyn 1981;4:410-417. https://doi.org/10.1248/bpb1978.4.410
  9. Xie JT, Mehendale SR, Wang A, Han AH, Wu JA, Osinski J, Yuan CS. American ginseng leaf: ginsenoside analysis and hypoglycemic activity. Pharmacol Res 2004;49:113-117. https://doi.org/10.1016/j.phrs.2003.07.015
  10. Xie JT, Mchendale S, Yuan CS. Ginseng and diabetes. Am J Chin Med 2005;33:397-404. https://doi.org/10.1142/S0192415X05003004
  11. Yun SN, Moon SJ, Ko SK, Im BO, Chung SH. Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice. Arch Pharm Res 2004;27:790-796. https://doi.org/10.1007/BF02980150
  12. Kimura I, Nakashima N, Sugihara Y, Fu-jun C, Kimura M. The antihyperglycaemic blend effect of traditional chinese medicine byakko-ka-ninjin-to on alloxan and diabetic KK-CA(y) mice. Phytother Res 1999;13:484-488. https://doi.org/10.1002/(SICI)1099-1573(199909)13:6<484::AID-PTR485>3.0.CO;2-X
  13. Chung SH, Choi CG, Park SH. Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice. Arch Pharm Res 2001;24:214-218. https://doi.org/10.1007/BF02978260
  14. Attele AS, Zhou YP, Xie JT, Wu JA, Zhang L, Dey L, Pugh W, Rue PA, Polonsky KS, Yuan CS. Antidiabetic effects of Panax ginseng berry extract and the identifi cation of an effective component. Diabetes 2002;51:1851-1858. https://doi.org/10.2337/diabetes.51.6.1851
  15. Xie JT, Zhou YP, Dey L, Attele AS, Wu JA, Gu M, Polonsky KS, Yuan CS. Ginseng berry reduces blood glucose and body weight in db/db mice. Phytomedicine 2002;9:254-258. https://doi.org/10.1078/0944-7113-00106
  16. Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean red ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci 2005;97:124-131. https://doi.org/10.1254/jphs.FP0040184
  17. Vuksan V, Stavro MP, Sievenpiper JL, Beljan-Zdravkovic U, Leiter LA, Josse RG, Xu Z. Similar postprandial glycemic reductions with escalation of dose and administration time of American ginseng in type 2 diabetes. Diabetes Care 2000;23:1221-1226. https://doi.org/10.2337/diacare.23.9.1221
  18. Vuksan V, Sievenpiper JL, Wong J, Xu Z, Beljan- Zdravkovic U, Arnason JT, Assinewe V, Stavro MP, Jenkins AL, Leiter LA et al. American ginseng (Panax quinquefolius L.) attenuates postprandial glycemia in a time-dependent but not dose-dependent manner in healthy individuals. Am J Clin Nutr 2001;73:753-758. https://doi.org/10.1093/ajcn/73.4.753
  19. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebocontrolled study of effi cacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  20. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS. Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine 2003;10:600-605. https://doi.org/10.1078/094471103322331908
  21. Kim YK, Yoo DS, Xu H, Park NI, Kim HH, Choi JE, Park SU. Ginsenoside content of berries and roots of three typical Korean ginseng (Panax ginseng) cultivars. Nat Prod Commun 2009;4:903-906.
  22. Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R et al. Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest 2003;112:1521-1532. https://doi.org/10.1172/JCI18581
  23. Mziaut H, Kersting S, Knoch KP, Fan WH, Trajkovski M, Erdmann K, Bergert H, Ehehalt F, Saeger HD, Solimena M. ICA512 signaling enhances pancreatic beta-cell proliferation by regulating cyclins D through STATs. Proc Natl Acad Sci U S A 2008;105:674-679. https://doi.org/10.1073/pnas.0710931105
  24. Flock G, Cao X, Drucker DJ. Pdx-1 is not suffi cient for repression of proglucagon gene transcription in islet or enteroendocrine cells. Endocrinology 2005;146:441-449. https://doi.org/10.1210/en.2004-0495
  25. Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan- Zdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009-1013. https://doi.org/10.1001/archinte.160.7.1009
  26. Sotaniemi EA, Haapakoski E, Rautio A. Ginseng therapy in non-insulin-dependent diabetic patients. Diabetes Care 1995;18:1373-1375. https://doi.org/10.2337/diacare.18.10.1373
  27. Xie JT, Wu JA, Mehendale S, Aung HH, Yuan CS. Antihyperglycemic effect of the polysaccharides fraction from American ginseng berry extract in ob/ob mice. Phytomedicine 2004;11:182-187. https://doi.org/10.1078/0944-7113-00325
  28. Dey L, Zhang L, Yuan CS. Anti-diabetic and anti-obese effects of ginseng berry extract: comparison between intraperitoneal and oral administrations. Am J Chin Med 2002;30:645-647. https://doi.org/10.1142/S0192415X02000648
  29. Buchanan TA. Pancreatic beta-cell loss and preservation in type 2 diabetes. Clin Ther 2003;25 Suppl B:B32-B46. https://doi.org/10.1016/S0149-2918(03)80241-2
  30. Hou JP. The chemical constituents of ginseng plants. Comp Med East West 1977;5:123-145. https://doi.org/10.1142/S0147291777000209
  31. Ji QC, Harkey MR, Henderson GL, Gershwin ME, Stern JS, Hackman RM. Quantitative determination of ginsenosides by high-performance liquid chromatography-tandem mass spectrometry. Phytochem Anal 2001;12:320-326. https://doi.org/10.1002/pca.593
  32. Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001;16 Suppl:S28-S37. https://doi.org/10.3346/jkms.2001.16.S.S28

Cited by

  1. ) Prevents Hyperglycemia and Associated Pancreatic Abnormalities in Diabetes vol.16, pp.7, 2013, https://doi.org/10.1089/jmf.2012.0192
  2. Ginseng Berry Extract Promotes Maturation of Mouse Dendritic Cells vol.10, pp.6, 2015, https://doi.org/10.1371/journal.pone.0130926
  3. Process Optimization of Ginseng Berry Extract Using Mixed Solvent and its Ginsenoside Analysis vol.16, pp.11, 2015, https://doi.org/10.5762/KAIS.2015.16.11.7794
  4. Diabetes Mellitus, Cognitive Impairment, and Traditional Chinese Medicine vol.2015, pp.1687-8345, 2015, https://doi.org/10.1155/2015/810439
  5. ) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement vol.2015, pp.1741-4288, 2015, https://doi.org/10.1155/2015/316527
  6. Effect of wild Korean ginseng (Panax ginseng) extract on blood glucose and serum lipid contents in rats with multiple low-dose streptozotocin-induced diabetes vol.24, pp.4, 2015, https://doi.org/10.1007/s10068-015-0194-9
  7. Ginseng Berry Extract Supplementation Improves Age-Related Decline of Insulin Signaling in Mice vol.7, pp.4, 2015, https://doi.org/10.3390/nu7043038
  8. Ginseng Berry Extract Attenuates Dextran Sodium Sulfate-Induced Acute and Chronic Colitis vol.8, pp.4, 2016, https://doi.org/10.3390/nu8040199
  9. Stereoselective and Simultaneous Analysis of Ginsenosides from Ginseng Berry Extract in Rat Plasma by UPLC-MS/MS: Application to a Pharmacokinetic Study of Ginseng Berry Extract vol.23, pp.7, 2018, https://doi.org/10.3390/molecules23071835
  10. 진생베리 열수 추출물의 다당체 분해 효소와 인슐린 신호전달 분자 PTP1B와 AKT1에 미치는 효과 vol.24, pp.9, 2012, https://doi.org/10.5352/jls.2014.24.9.1006
  11. A review on the medicinal potential of Panax ginseng saponins in diabetes mellitus vol.5, pp.59, 2012, https://doi.org/10.1039/c5ra05864c
  12. Plant-Derived Compounds Targeting Pancreatic Beta Cells for the Treatment of Diabetes vol.2015, pp.None, 2012, https://doi.org/10.1155/2015/629863
  13. 발효 김치로부터 분리한 Lactobacillus sp. Strain KYH를 이용한 진생베리 추출물 최적 발효 공정 확립 및 생성물의 특성 분석 vol.26, pp.1, 2012, https://doi.org/10.17495/easdl.2016.2.26.1.88
  14. Are berries useless by-products of ginseng? Recent research on the potential health benefits of ginseng berry vol.16, pp.None, 2012, https://doi.org/10.17179/excli2017-376
  15. Effect of ginseng therapy on diabetes and its chronic complications: lessons learned vol.14, pp.4, 2012, https://doi.org/10.1515/jcim-2016-0166
  16. Effect of ginseng therapy on diabetes and its chronic complications: lessons learned vol.14, pp.4, 2012, https://doi.org/10.1515/jcim-2016-0166
  17. Antihypertensive effects of Korean wild simulated ginseng (Sanyangsam) extracts in spontaneously hypertensive rats vol.28, pp.5, 2012, https://doi.org/10.1007/s10068-019-00617-5
  18. Review of Ginseng Anti-Diabetic Studies vol.24, pp.24, 2012, https://doi.org/10.3390/molecules24244501
  19. 고려인삼과 당뇨병: 세포와 동물 및 인체실험을 통한 고려인삼의 당뇨병에 대한 효능 vol.51, pp.1, 2012, https://doi.org/10.22889/kjp.2020.51.1.001
  20. Immune enhancement effects of Korean ginseng berry polysaccharides on RAW264.7 macrophages through MAPK and NF-κB signalling pathways vol.32, pp.1, 2021, https://doi.org/10.1080/09540105.2021.1934419
  21. Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus vol.2021, pp.None, 2012, https://doi.org/10.1155/2021/2920530
  22. The effects of ginseng on the metabolic syndrome: An updated review vol.9, pp.9, 2021, https://doi.org/10.1002/fsn3.2475