Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Chronic saponin treatment attenuates damage to the pancreas in chronic alcohol-treated diabetic rats

  • Choi, Mi Ran (Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Kwak, Su Min (Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Bang, Sol Hee (Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Jeong, Jo-Eun (Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine) ;
  • Kim, Dai-Jin (Department of Psychiatry, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine)
  • Received : 2016.01.06
  • Accepted : 2016.09.27
  • Published : 2017.10.15
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Abstract

Background: Chronic heavy alcohol consumption may raise the risk of developing type 2 diabetes mellitus. Saponins inhibit apoptosis of pancreatic islet cells and reduce lipid parameters. The present study was designed to investigate the effect of saponin on chronic ethanol-treated diabetic rats. Methods: Long-Evans Tokushima Fatty (LETO) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats were pair-fed a Lieber-DeCarli diet with and without 5% ethanol for 12 wks. Two weeks after starting the pair-feeding with the Lieber-DeCarli diet, intraperitoneal injection of saponin was performed for 10 wks. To perform the experiments, rats were divided as follows: LETO-Control (LC), LETO-Ethanol (LE), LETO-Ethanol-Saponin (LES), OLETF-Control (OC), OLETF-Ethanol (OE), and OLETF-Ethanol-Saponin (OES). Results: The weights of epididymal and mesenteric fat tissue in LES and OES rats were the lightest from among the LETO and OLETF groups, respectively. The secretion of alanine aminotransferase and cholesterol in OES rats decreased significantly compared to their secretion in OC and OE rats, respectively. The islets of the pancreas in LE and OE rats showed clean, unclear, and smaller morphology compared to those of LC, LES, OC, and OES rats. In addition, the expression of insulin in the islets of the pancreas in LC, LES, OC, and OES rats was higher than in LE and OE rats. Conclusion: Saponin may not only be helpful in alleviating the rapid progress of diabetes due to chronic alcohol consumption in diabetic patients, but may also show potential as an antidiabetic drug candidate for diabetic patients who chronically consume alcohol.

Keywords

References

  1. Hodge AM, Dowse GK, Collins VR, Zimmet PZ. Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus. Am J Epidemiol 1993;137:178-89. https://doi.org/10.1093/oxfordjournals.aje.a116658
  2. Patel SB, Santani D, Patel V, Shah M. Anti-diabetic effects of ethanol extract of Bryonia laciniosa seeds and its saponins rich fraction in neonatally streptozotocin-induced diabetic rats. Pharmacognosy Res 2015;7:92-9. https://doi.org/10.4103/0974-8490.147217
  3. Kim JY, Park KJ, Kim GH, Jeong EA, Lee DY, Lee SS, Kim DJ, Roh GS, Song J, Ki SH, et al. In vivo activating transcription factor 3 silencing ameliorates the AMPK compensatory effects for ER stress-mediated beta-cell dysfunction during the progression of type-2 diabetes. Cell Signal 2013;25:2348-61. https://doi.org/10.1016/j.cellsig.2013.07.028
  4. Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, Tuncman G, Gorgun C, Glimcher LH, Hotamisligil GS. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004;306:457-61. https://doi.org/10.1126/science.1103160
  5. Reynolds K, Lewis B, Nolen JD, Kinney GL, Sathya B, He J. Alcohol consumption and risk of stroke: a meta-analysis. JAMA 2003;289:579-88. https://doi.org/10.1001/jama.289.5.579
  6. Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN. Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care 2000;23:18-22. https://doi.org/10.2337/diacare.23.1.18
  7. Fueki Y, Miida T, Wardaningsih E, Ito M, Nakamura A, Takahashi A, Hanyu O, Tsuda A, Saito H, Hama H, et al. Regular alcohol consumption improves insulin resistance in healthy Japanese men independent of obesity. Clin Chim Acta 2007;382:71-6. https://doi.org/10.1016/j.cca.2007.03.027
  8. Kim JY, Song EH, Lee HJ, Oh YK, Park YS, Park JW, Kim BJ, Kim DJ, Lee I, Song J, et al. Chronic ethanol consumption-induced pancreatic {beta}-cell dysfunction and apoptosis through glucokinase nitration and its down-regulation. J Biol Chem 2010;285:37251-62. https://doi.org/10.1074/jbc.M110.142315
  9. Lee SS, Hong OK, Ju A, Kim MJ, Kim BJ, Kim SR, Kim WH, Cho NH, Kang MI, Kang SK, et al. Chronic alcohol consumption results in greater damage to the pancreas than to the liver in the rats. Korean J Physiol Pharmacol 2015;19:309-18. https://doi.org/10.4196/kjpp.2015.19.4.309
  10. Talamini G, Bassi C, Falconi M, Sartori N, Salvia R, Rigo L, Castagnini A, Di Francesco V, Frulloni L, Bovo P, et al. Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci 1999;44:1303-11. https://doi.org/10.1023/A:1026670911955
  11. Elekofehinti OO. Saponins: anti-diabetic principles from medicinal plants - a review. Pathophysiology 2015;22:95-103. https://doi.org/10.1016/j.pathophys.2015.02.001
  12. Kuate D, Kengne AP, Biapa CP, Azantsa BG, Abdul Manan Bin Wan Muda W. Tetrapleura tetraptera spice attenuates high-carbohydrate, high-fat dietinduced obese and type 2 diabetic rats with metabolic syndrome features. Lipids Health Dis 2015;14:50. https://doi.org/10.1186/s12944-015-0051-0
  13. Elekofehinti OO, Kamdem JP, Kade IJ, Rocha JBT, Adanlawo IG. Hypoglycemic, antiperoxidative and antihyperlipidemic effects of saponins from Solanum anguivi Lam. fruits in alloxan-induced diabetic rats. S Afr J Bot 2013;88:56-61. https://doi.org/10.1016/j.sajb.2013.04.010
  14. Kim HY, Kim K. Protective effect of ginseng on cytokine-induced apoptosis in pancreatic beta-cells. J Agric Food Chem 2007;55:2816-23. https://doi.org/10.1021/jf062577r
  15. Lim KH, Cho JY, Kim B, Bae BS, Kim JH. Red ginseng (Panax ginseng) decreases isoproterenol-induced cardiac injury via antioxidant properties in porcine. J Med Food 2014;17:111-8. https://doi.org/10.1089/jmf.2013.2768
  16. Jung KI, Ju A, Lee HM, Lee SS, Song CH, Won WY, Jeong JS, Hong OK, Kim JH, Kim DJ. Chronic ethanol ingestion, type 2 diabetes mellitus, and brain-derived neurotrophic factor (BDNF) in rats. Neurosci Lett 2011;487:149-52. https://doi.org/10.1016/j.neulet.2010.10.011
  17. Kawano K, Hirashima T, Mori S, Saitoh Y, Kurosumi M, Natori T. Spontaneous long-term hyperglycemic rat with diabetic complications. Otsuka Long-Evans Tokushima Fatty (OLETF) strain. Diabetes 1992;41:1422-8. https://doi.org/10.2337/diab.41.11.1422
  18. Rector RS, Uptergrove GM, Borengasser SJ, Mikus CR, Morris EM, Naples SP, Laye MJ, Laughlin MH, Booth FW, Ibdah JA, et al. Changes in skeletal muscle mitochondria in response to the development of type 2 diabetes or prevention by daily wheel running in hyperphagic OLETF rats. Am J Physiol Endocrinol Metab 2010;298:E1179-87. https://doi.org/10.1152/ajpendo.00703.2009
  19. 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;97:124-31. https://doi.org/10.1254/jphs.FP0040184
  20. Brocardo PS, Boehme F, Patten A, Cox A, Gil-Mohapel J, Christie BR. Anxiety- and depression-like behaviors are accompanied by an increase in oxidative stress in a rat model of fetal alcohol spectrum disorders: protective effects of voluntary physical exercise. Neuropharmacology 2012;62:1607-18. https://doi.org/10.1016/j.neuropharm.2011.10.006
  21. Patki G, Solanki N, Atrooz F, Allam F, Salim S. Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 2013;1539:73-86. https://doi.org/10.1016/j.brainres.2013.09.033
  22. Kim SJ, Ju A, Lim SG, Kim DJ. Chronic alcohol consumption, type 2 diabetes mellitus, insulin-like growth factor-I (IGF-I), and growth hormone (GH) in ethanol-treated diabetic rats. Life Sci 2013;93:778-82. https://doi.org/10.1016/j.lfs.2013.09.018
  23. Lavorato-Rocha AM, Anjos LG, Cunha IW, Vassallo J, Soares FA, Rocha RM. Immunohistochemical assessment of PTEN in vulvar cancer: best practices for tissue staining, evaluation, and clinical association. Methods 2015;77-78:20-4. https://doi.org/10.1016/j.ymeth.2014.12.017
  24. Risinger FO, Cunningham CL. Genetic differences in ethanol-induced hyperglycemia and conditioned taste aversion. Life Sci 1992;50:Pl113-8.
  25. Ali S, Stone MA, Peters JL, Davies MJ, Khunti K. The prevalence of co-morbid depression in adults with Type 2 diabetes: a systematic review and meta-analysis. Diabet Med 2006;23:1165-73. https://doi.org/10.1111/j.1464-5491.2006.01943.x
  26. Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001;24:1069-78. https://doi.org/10.2337/diacare.24.6.1069
  27. Ates M, Dayi A, Kiray M, Sisman AR, Agilkaya S, Aksu I, Baykara B, Buyuk E, Cetinkaya C, Cingoz S, et al. Anxiety- and depression-like behavior are correlated with leptin and leptin receptor expression in prefrontal cortex of streptozotocin-induced diabetic rats. Biotech Histochem 2014;89:161-71. https://doi.org/10.3109/10520295.2013.825319
  28. George FR, Collins AC. Prostaglandin synthetase inhibitors antagonize the depressant effects of ethanol. Pharmacol Biochem Behav 1979;10:865-9. https://doi.org/10.1016/0091-3057(79)90059-5
  29. Abbas G, Rauf K, Mahmood W. Saponins: the phytochemical with an emerging potential for curing clinical depression. Nat Prod Res 2015;29:302-7. https://doi.org/10.1080/14786419.2014.942661
  30. Chen L, Dai J, Wang Z, Zhang H, Huang Y, Zhao Y. The antidepressant effects of ginseng total saponins in male C57BL/6N mice by enhancing hippocampal inhibitory phosphorylation of GSK-3beta. Phytother Res 2014;28:1102-6. https://doi.org/10.1002/ptr.5103
  31. Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, Halavaara J, Yki-Jarvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002;87:3023-8. https://doi.org/10.1210/jcem.87.7.8638
  32. Tiikkainen M, Bergholm R, Vehkavaara S, Rissanen A, Hakkinen AM, Tamminen M, Teramo K, Yki-Jarvinen H. Effects of identical weight loss on body composition and features of insulin resistance in obese women with high and low liver fat content. Diabetes 2003;52:701-7. https://doi.org/10.2337/diabetes.52.3.701
  33. Celik S, Erdogan S, Tuzcu M. Caffeic acid phenethyl ester (CAPE) exhibits significant potential as an antidiabetic and liver-protective agent in streptozotocin-induced diabetic rats. Pharmacol Res 2009;60:270-6. https://doi.org/10.1016/j.phrs.2009.03.017
  34. Shinde UA, Goyal RK. Effect of chromium picolinate on histopathological alterations in STZ and neonatal STZ diabetic rats. J Cell Mol Med 2003;7:322-9. https://doi.org/10.1111/j.1582-4934.2003.tb00233.x
  35. Sandler S, Bendtzen K, Eizirik DL, Welsh M. Interleukin-6 affects insulin secretion and glucose metabolism of rat pancreatic islets in vitro. Endocrinology 1990;126:1288-94. https://doi.org/10.1210/endo-126-2-1288
  36. Southern C, Schulster D, Green IC. Inhibition of insulin secretion from rat islets of Langerhans by interleukin-6. An effect distinct from that of interleukin-1. Biochem J 1990;272:243-5. https://doi.org/10.1042/bj2720243
  37. Prystupa A, Kicinski P, Sak J, Boguszewska-Czubara A, Torun-Jurkowska A, Zaluska W. Proinflammatory cytokines (IL-1alpha, IL-6) and hepatocyte growth factor in patients with alcoholic liver cirrhosis. Gastroenterol Res Pract 2015;2015, 532615.
  38. Aravinthan A, Kim JH, Antonisamy P, Kang CW, Choi J, Kim NS, Kim JH. Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties. J Ginseng Res 2015;39:206-12. https://doi.org/10.1016/j.jgr.2014.12.001
  39. Liu HZ, Liu ZL, Zhao SP, Sun CZ, Yang MS. Protective mechanism of Panax notoginseng saponins on rat hemorrhagic shock model in recovery stage. Cell Biochem Biophys 2014;70:1719-24. https://doi.org/10.1007/s12013-014-0119-x
  40. Abbate SL, Brunzell JD. Pathophysiology of hyperlipidemia in diabetes mellitus. J Cardiovasc Pharmacol 1990;16(Suppl 9):S1-7.
  41. Oki JC. Dyslipidemias in patients with diabetes mellitus: classification and risks and benefits of therapy. Pharmacotherapy 1995;15:317-37.
  42. Kelley DE, Goodpaster BH. Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance. Diabetes Care 2001;24:933-41. https://doi.org/10.2337/diacare.24.5.933
  43. Tammi A, Ronnemaa T, Gylling H, Rask-Nissila L, Viikari J, Tuominen J, Pulkki K, Simell O. Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children: the STRIP project. Special Turku Coronary Risk Factors Intervention Project. J Pediatr 2000;136:503-10. https://doi.org/10.1016/S0022-3476(00)90014-3
  44. Dembele K, Nguyen KH, Hernandez TA, Nyomba BL. Effects of ethanol on pancreatic beta-cell death: interaction with glucose and fatty acids. Cell Biol Toxicol 2009;25:141-52. https://doi.org/10.1007/s10565-008-9067-9
  45. Kim SS, Jang HJ, Oh MY, Eom DW, Kang KS, Kim YJ, Lee JH, Ham JY, Choi SY, Wee YM, et al. Ginsenoside Rg3 enhances islet cell function and attenuates apoptosis in mouse islets. Transplant Proc 2014;46:1150-5. https://doi.org/10.1016/j.transproceed.2013.12.028
  46. Luo JZ, Luo L. American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells. Evid Based Complement Alternat Med 2006;3:36-72.

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