Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2017 | Research article

GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats

Authors: Chan-Sik Kim, Kyuhyung Jo, Jin Sook Kim, Mi-Kyung Pyo, Junghyun Kim

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Abstract

Background

GS-E3D is a newly developed pectin lyase-modified red ginseng extract. The purpose of this study was to investigate the therapeutic effects of GS-E3D on diabetes-related renal dysfunction in streptozotocin-induced diabetic rats.

Method

GS-E3D (25, 50, and 100 mg/kg body weight per day) was administered for 6 weeks. The levels of blood glucose and hemoglobin A1c, and of urinary albumin, 8-hydroxy-2′-deoxyguanosine (8-OHdG), and advanced glycation end-products (AGEs) were determined. Kidney histopathology, renal accumulation of AGEs, and expression of α-smooth muscle actin (α-SMA) were also examined.

Results

Administration of GS-E3D for 6 weeks reduced urinary levels of albumin, 8-OHdG, and AGEs in diabetic rats. Mesangial expansion, renal accumulation of AGEs, and enhanced α-SMA expression were significantly inhibited by GS-E3D treatment. Oral administration of GS-E3D dose-dependently improved all symptoms of diabetic nephropathy by inhibiting renal accumulation of AGEs and oxidative stress.

Conclusion

The results of this study indicate that the use of GS-E3D as a food supplement may provide effective treatment of diabetes-induced renal dysfunction.

White KE, Bilous RW. Type 2 diabetic patients with nephropathy show structural-functional relationships that are similar to type 1 disease. J Am Soc Nephrol. 2000;11(9):1667–73.PubMed

Kanwar YS, Wada J, Sun L, Xie P, Wallner EI, Chen S, Chugh S, Danesh FR. Diabetic nephropathy: mechanisms of renal disease progression. Exp Biol Med. 2008;233(1):4–11.CrossRef

Kang AY, Park SK, Park SY, Lee HJ, Han Y, Lee SR, Suh SH, Kim DK, Park MK. Therapeutic target achievement in type 2 diabetic patients after hyperglycemia, hypertension, dyslipidemia management. Diabetes Metab J. 2011;35(3):264–72.CrossRefPubMedPubMedCentral

Satirapoj B, Adler SG. Prevalence and Management of Diabetic Nephropathy in western countries. Kidney Dis. 2015;1(1):61–70.CrossRef

Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40(4):405–12.CrossRefPubMed

Brownlee M. Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995;46:223–34.CrossRefPubMed

Forbes JM, Coughlan MT, Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes. 2008;57(6):1446–54.CrossRefPubMed

Nistala R, Whaley-Connell A, Sowers JR. Redox control of renal function and hypertension. Antioxid Redox Signal. 2008;10(12):2047–89.CrossRefPubMedPubMedCentral

Yan SD, Yan SF, Chen X, Fu J, Chen M, Kuppusamy P, Smith MA, Perry G, Godman GC, Nawroth P, et al. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nat Med. 1995;1(7):693–9.CrossRefPubMed

10.

Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010;107(9):1058–70.CrossRefPubMedPubMedCentral

11.

Yan SF, Ramasamy R, Naka Y, Schmidt AM. Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ Res. 2003;93(12):1159–69.CrossRefPubMed

12.

Moore KJ, Freeman MW. Scavenger receptors in atherosclerosis: beyond lipid uptake. Arterioscler Thromb Vasc Biol. 2006;26(8):1702–11.CrossRefPubMed

13.

Yamamoto Y, Yamamoto H. Interaction of receptor for advanced glycation end products with advanced oxidation protein products induces podocyte injury. Kidney Int. 2012;82(7):733–5.CrossRefPubMed

14.

Chuang PY, Yu Q, Fang W, Uribarri J, He JC. Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor. Kidney Int. 2007;72(8):965–76.CrossRefPubMedPubMedCentral

15.

Ahmed N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res Clin Pract. 2005;67(1):3–21.CrossRefPubMed

16.

Rahbar S, Figarola JL. Novel inhibitors of advanced glycation endproducts. Arch Biochem Biophys. 2003;419(1):63–79.CrossRefPubMed

17.

Peppa M, Brem H, Cai W, Zhang JG, Basgen J, Li Z, Vlassara H, Uribarri J. Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711). Am J Nephrol. 2006;26(5):430–6.CrossRefPubMed

18.

Suji G, Sivakami S. DNA damage by free radical production by aminoguanidine. Ann N Y Acad Sci. 2006;1067:191–9.CrossRefPubMed

19.

Tilton RG, Chang K, Hasan KS, Smith SR, Petrash JM, Misko TP, Moore WM, Currie MG, Corbett JA, McDaniel ML, et al. Prevention of diabetic vascular dysfunction by guanidines. Inhibition of nitric oxide synthase versus advanced glycation end-product formation. Diabetes. 1993;42(2):221–32.CrossRefPubMed

20.

Osawa T, Kato Y. Protective role of antioxidative food factors in oxidative stress caused by hyperglycemia. Ann N Y Acad Sci. 2005;1043:440–51.CrossRefPubMed

21.

Hong SY, Oh JH, Lee I. Simultaneous enrichment of deglycosylated ginsenosides and monacolin K in red ginseng by fermentation with Monascus Pilosus. Biosci Biotechnol Biochem. 2011;75(8):1490–5.CrossRefPubMed

22.

Kim P, Park JH, Kwon KJ, Kim KC, Kim HJ, Lee JM, Kim HY, Han SH, Shin CY. Effects of Korean red ginseng extracts on neural tube defects and impairment of social interaction induced by prenatal exposure to valproic acid. Food Chem Toxicol. 2013;51:288–96.CrossRefPubMed

23.

Park HM, Kim SJ, Mun AR, Go HK, Kim GB, Kim SZ, Jang SI, Lee SJ, Kim JS, Kang HS. Korean red ginseng and its primary ginsenosides inhibit ethanol-induced oxidative injury by suppression of the MAPK pathway in TIB-73 cells. J Ethnopharmacol. 2012;141(3):1071–6.CrossRefPubMed

24.

Paul S, Shin HS, Kang SC. Inhibition of inflammations and macrophage activation by ginsenoside-re isolated from Korean ginseng (Panax Ginseng C.A. Meyer). Food Chem Toxicol. 2012;50(5):1354–61.CrossRefPubMed

25.

Wang CZ, Anderson S, Du W, He TC, Yuan CS. Red ginseng and cancer treatment. Chin J Nat Med. 2016;14(1):7–16.PubMed

26.

Hosseini A, Ghorbani A. Cancer therapy with phytochemicals: evidence from clinical studies. Avicenna J Phytomedicine. 2015;5(2):84–97.

27.

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(1):124–31.CrossRefPubMed

28.

Liu TP, Liu IM, Cheng JT. Improvement of insulin resistance by panax ginseng in fructose-rich chow-fed rats. Horm Metab Res. 2005;37(3):146–51.CrossRefPubMed

29.

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, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis. 2008;18(1):46–56.CrossRefPubMed

30.

Hong YJ, Kim N, Lee K, Hee Sonn C, Eun Lee J, Tae Kim S, Ho Baeg I, Lee KM. Korean red ginseng (Panax Ginseng) ameliorates type 1 diabetes and restores immune cell compartments. J Ethnopharmacol. 2012;144(2):225–33.CrossRefPubMed

31.

Park S, Kim CS, Min J, Lee SH, Jung YS. A high-fat diet increases oxidative renal injury and protein glycation in D-galactose-induced aging rats and its prevention by Korea red ginseng. J Nutr Sci Vitaminol. 2014;60(3):159–66.CrossRefPubMed

32.

Quan HY, Kim DY, Chung SH. Korean red ginseng extract alleviates advanced glycation end product-mediated renal injury. J Ginseng Res. 2013;37(2):187–93.CrossRefPubMedPubMedCentral

33.

Ko SR, Choi KJ, Uchida K, Suzuki Y. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1 from protopanaxatriol-type ginseng saponin mixture. Planta Med. 2003;69(3):285–6.CrossRefPubMed

34.

Park CS, Yoo MH, Noh KH, Oh DK. Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl Microbiol Biotechnol. 2010;87(1):9–19.CrossRefPubMed

35.

Cheon JM, Kim DI, Kim KS. Insulin sensitivity improvement of fermented Korean red ginseng (Panax Ginseng) mediated by insulin resistance hallmarks in old-aged ob/ob mice. J Ginseng Res. 2015;39(4):331–7.CrossRefPubMedPubMedCentral

36.

Park SY, Kim HB, Kim JH, Lee JM, Kim SR, Shin HS, Yi TH. Immunostimulatory effect of fermented red ginseng in the mouse model. Prev Nutr Food Sci. 2014;19(1):10–8.CrossRefPubMedPubMedCentral

37.

Oh J, Lee SR, Hwang KT, Ji GE. The anti-obesity effects of the dietary combination of fermented red ginseng with levan in high fat diet mouse model. Phytother Res. 2014;28(4):617–22.CrossRefPubMed

38.

Lee EJ, Song MJ, Kwon HS, Ji GE, Sung MK. Oral administration of fermented red ginseng suppressed ovalbumin-induced allergic responses in female BALB/c mice. Phytomedicine. 2012;19(10):896–903.CrossRefPubMed

39.

Wang HY, Qi LW, Wang CZ, Li P. Bioactivity enhancement of herbal supplements by intestinal microbiota focusing on ginsenosides. Am J Chin Med. 2011;39(6):1103–15.CrossRefPubMedPubMedCentral

40.

Kim HJ, Lee SG, Chae IG, Kim MJ, Im NK, Yu MH, Lee EJ, Lee IS. Antioxidant effects of fermented red ginseng extracts in streptozotocin- induced diabetic rats. J Ginseng Res. 2011;35(2):129–37.CrossRefPubMedPubMedCentral

41.

Lee HY, Park KH, Park YM, Moon DI, Oh HG, Kwon DY, Yang HJ, Kim O, Kim DW, Yoo JH, et al. Effects of pectin lyase-modified red ginseng extracts in high-fat diet-fed obese mice. Lab Anim Res. 2014;30(4):151–60.CrossRefPubMedPubMedCentral

42.

Hong SC, Oh MH, Lee H, Park YS, Kim NY, Park SH, Park JD, Jang JD, Kim SH, Kim EJ, et al. Pectinase-modified red ginseng (GS-E3D) inhibit NF-ΚB translocation and nitric oxide production in lipoplysaccharide-stimulated RAW 264.7 cells. Int J Pharm Pharm Sci. 2015;7(9):322–5.

43.

Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillere-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drueke T, Descamps-Latscha B. Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol. 1998;161(5):2524–32.PubMed

44.

Guo ZJ, Niu HX, Hou FF, Zhang L, Fu N, Nagai R, Lu X, Chen BH, Shan YX, Tian JW, et al. Advanced oxidation protein products activate vascular endothelial cells via a RAGE-mediated signaling pathway. Antioxid Redox Signal. 2008;10(10):1699–712.CrossRefPubMed

45.

Brosius FC 3rd. New insights into the mechanisms of fibrosis and sclerosis in diabetic nephropathy. Rev Endocr Metab Disord. 2008;9(4):245–54.CrossRefPubMedPubMedCentral

46.

Johnson RJ, Iida H, Alpers CE, Majesky MW, Schwartz SM, Pritzi P, Gordon K, Gown AM. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest. 1991;87(3):847–58.CrossRefPubMedPubMedCentral

47.

Siu B, Saha J, Smoyer WE, Sullivan KA, Brosius FC 3rd. Reduction in podocyte density as a pathologic feature in early diabetic nephropathy in rodents: prevention by lipoic acid treatment. BMC Nephrol. 2006;7:6.CrossRefPubMedPubMedCentral

48.

Young BA, Johnson RJ, Alpers CE, Eng E, Gordon K, Floege J, Couser WG, Seidel K. Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int. 1995;47(3):935–44.CrossRefPubMed

49.

Wolf G, Sharma K, Chen Y, Ericksen M, Ziyadeh FN. High glucose-induced proliferation in mesangial cells is reversed by autocrine TGF-beta. Kidney Int. 1992;42(3):647–56.CrossRefPubMed

50.

Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Fujita T. Angiotensin II blockade restores albumin reabsorption in the proximal tubules of diabetic rats. Hypertens Res. 2003;26(5):413–9.CrossRefPubMed

51.

Fujii M, Inoguchi T, Maeda Y, Sasaki S, Sawada F, Saito R, Kobayashi K, Sumimoto H, Takayanagi R. Pitavastatin ameliorates albuminuria and renal mesangial expansion by downregulating NOX4 in db/db mice. Kidney Int. 2007;72(4):473–80.CrossRefPubMed

52.

Tan Z, Xu Z, Gui Q, Wu W, Yang Y. Gliquidone versus metformin: differential effects on aorta in streptozotocin induced diabetic rats. Chin Med J. 2014;127(7):1298–303.PubMed

53.

Liu WJ, Xie SH, Liu YN, Kim W, Jin HY, Park SK, Shao YM, Park TS. Dipeptidyl peptidase IV inhibitor attenuates kidney injury in streptozotocin-induced diabetic rats. J Pharmacol Exp Ther. 2012;340(2):248–55.CrossRefPubMed

54.

Davidson EP, Coppey LJ, Dake B, Yorek MA. Treatment of streptozotocin-induced diabetic rats with alogliptin: effect on vascular and neural complications. Exp Diabetes Res. 2011;2011:810469.CrossRefPubMedPubMedCentral

55.

Coughlan MT, Mibus AL, Forbes JM. Oxidative stress and advanced glycation in diabetic nephropathy. Ann N Y Acad Sci. 2008;1126:190–3.CrossRefPubMed

56.

Fukami K, Yamagishi S, Ueda S, Okuda S. Role of AGEs in diabetic nephropathy. Curr Pharm Des. 2008;14(10):946–52.CrossRefPubMed

57.

Soler MJ, Riera M, Batlle D. New experimental models of diabetic nephropathy in mice models of type 2 diabetes: efforts to replicate human nephropathy. Exp Diabetes Res. 2012;2012:616313.CrossRefPubMedPubMedCentral

58.

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005;54(6):1615–25.CrossRefPubMed

59.

Berrou J, Tostivint I, Verrecchia F, Berthier C, Boulanger E, Mauviel A, Marti HP, Wautier MP, Wautier JL, Rondeau E, et al. Advanced glycation end products regulate extracellular matrix protein and protease expression by human glomerular mesangial cells. Int J Mol Med. 2009;23(4):513–20.PubMed

60.

Luo ZF, Feng B, Mu J, Qi W, Zeng W, Guo YH, Pang Q, Ye ZL, Liu L, Yuan FH. Effects of 4-phenylbutyric acid on the process and development of diabetic nephropathy induced in rats by streptozotocin: regulation of endoplasmic reticulum stress-oxidative activation. Toxicol Appl Pharmacol. 2010;246(1–2):49–57.CrossRefPubMed

61.

Li H, Wang F, Zhang L, Cao Y, Liu W, Hao J, Liu Q, Duan H. Modulation of Nrf2 expression alters high glucose-induced oxidative stress and antioxidant gene expression in mouse mesangial cells. Cell Signal. 2011;23(10):1625–32.CrossRefPubMed

62.

Thallas-Bonke V, Thorpe SR, Coughlan MT, Fukami K, Yap FY, Sourris KC, Penfold SA, Bach LA, Cooper ME, Forbes JM. Inhibition of NADPH oxidase prevents advanced glycation end product-mediated damage in diabetic nephropathy through a protein kinase C-alpha-dependent pathway. Diabetes. 2008;57(2):460–9.CrossRefPubMed

63.

Hong SH, Suk KT, Choi SH, Lee JW, Sung HT, Kim CH, Kim EJ, Kim MJ, Han SH, Kim MY, et al. Anti-oxidant and natural killer cell activity of Korean red ginseng (Panax Ginseng) and urushiol (Rhus Vernicifera Stokes) on non-alcoholic fatty liver disease of rat. Food Chem Toxicol. 2013;55:586–91.CrossRefPubMed

64.

Yang H, Lee SE, Jeong SI, Park CS, Jin YH, Park YS. Up-regulation of Heme Oxygenase-1 by Korean red ginseng water extract as a Cytoprotective effect in human endothelial cells. J Ginseng Res. 2011;35(3):352–9.CrossRefPubMedPubMedCentral

65.

Sohn E, Kim J, Kim CS, Jo K, Kim JS. Extract of Rhizoma Polygonum Cuspidatum reduces early renal podocyte injury in streptozotocininduced diabetic rats and its active compound emodin inhibits methylglyoxalmediated glycation of proteins. Mol Med Rep. 2015;12(4):5837–45.CrossRefPubMedPubMedCentral

66.

Jung DH, Kim YS, Kim NH, Lee J, Jang DS, Kim JS. Extract of Cassiae semen and its major compound inhibit S100b-induced TGF-beta1 and fibronectin expression in mouse glomerular mesangial cells. Eur J Pharmacol. 2010;641(1):7–14.CrossRefPubMed

67.

Sohn E, Kim J, Kim CS, Lee YM, Jo K, Shin SD, Kim JH, Kim JS. The extract of Litsea Japonica reduced the development of diabetic nephropathy via the inhibition of advanced Glycation end products accumulation in db/db mice. Evid Based Complement Alternat Med. 2013;2013:769416.CrossRefPubMedPubMedCentral

68.

Yin J, Zhang H, Ye J. Traditional chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets. 2008;8(2):99–111.CrossRefPubMedPubMedCentral

69.

Doh KC, Lim SW, Piao SG, Jin L, Heo SB, Zheng YF, Bae SK, Hwang GH, Min KI, Chung BH, et al. Ginseng treatment attenuates chronic cyclosporine nephropathy via reducing oxidative stress in an experimental mouse model. Am J Nephrol. 2013;37(5):421–33.CrossRefPubMed

70.

Yokozawa T, Liu ZW, Dong E. A study of ginsenoside-rd in a renal ischemia-reperfusion model. Nephron. 1998;78(2):201–6.CrossRefPubMed

71.

Yokozawa T, Owada S. Effect of ginsenoside-rd in cephaloridine-induced renal disorder. Nephron. 1999;81(2):200–7.CrossRefPubMed

72.

Yokozawa T, Liu ZW. The role of ginsenoside-rd in cisplatin-induced acute renal failure. Ren Fail. 2000;22(2):115–27.CrossRefPubMed

73.

Chu JM, Lee DK, Wong DP, Wong RN, Yung KK, Cheng CH, Yue KK. Ginsenosides attenuate methylglyoxal-induced impairment of insulin signaling and subsequent apoptosis in primary astrocytes. Neuropharmacology. 2014;85:215–23.CrossRefPubMed

74.

Yokozawa T, Iwano M, Dohi K, Hattori M, Oura H. Inhibitory effects of ginseng on proliferation of cultured mouse mesangial cells. Japanese journal of nephrology. 1994;36(1):13–8.PubMed

Title: GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats
Authors: Chan-Sik Kim
Kyuhyung Jo
Jin Sook Kim
Mi-Kyung Pyo
Junghyun Kim
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-017-1925-7

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats

Abstract

Background

Method

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2017

Complementary traditional Chinese medicine use in Children with cerebral palsy: a nationwide retrospective cohort study in Taiwan

Antibacterial activity of crude extracts of some South African medicinal plants against multidrug resistant etiological agents of diarrhoea

Isolation of anti-mycobacterial compounds from Curtisia dentata (Burm.f.) C.A.Sm (Curtisiaceae)

Cheongsangbangpung-tang ameliorated the acute inflammatory response via the inhibition of NF-κB activation and MAPK phosphorylation

Protective effects of synbiotic diets of Bacillus coagulans, Lactobacillus plantarum and inulin against acute cadmium toxicity in rats

Edible bird’s nest modulate intracellular molecular pathways of influenza A virus infected cells