Journal of Ginseng Research

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

DOI QR Code

Korean red ginseng extract alleviates advanced glycation end product-mediated renal injury

  • Quan, Hai Yan (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University) ;
  • Kim, Do Yeon (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University) ;
  • Chung, Sung Hyun (Department of Pharmacology and Clinical Pharmacy, College of Pharmacy, Kyung Hee University)
  • Received : 2012.08.03
  • Accepted : 2012.11.07
  • Published : 2013.04.15
Download PDF
⟨ Previous Next ⟩

Abstract

The effect of Korean red ginseng (KRG) on diabetic renal damage was investigated using streptozotocin (STZ)-induced diabetic rats. The diabetic rats showed loss of body weight gain, and increases in kidney weight and urine volume, whereas the oral administration of KRG at a dose of 100 or 250 mg/kg of body weight per day for 28 d prevented these diabetes-induced physiological abnormalities. Among the kidney function parameters, elevated plasma levels of urea nitrogen and creatinine in diabetic control rats tended to be lowered in KRG-treated rats. In addition, administration of KRG at a dose of 100 mg/kg body weight in the diabetic rats showed significant decreases in serum glucose and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), implying that KRG might prevent the pathogenesis of diabetic complications caused by impaired glucose metabolism and oxidative stress. KRG also significantly reduced advanced glycation end product (AGE) formation and secretion from kidney of diabetic rats. Furthermore, KRG decreased the levels of N-(carboxymethyl) lysine and expression of AGE receptor. KRG also reduced the overexpression of cyclooxygenase-2 and inducible nitric oxide synthase in the kidney via deactivation of nuclear factor-kappa B. We also found that KRG prevented STZ-induced destruction of glomerular structure and significantly suppressed high glucose-induced fibronectin production. Taken together, KRG ameliorates abnormalities associated with diabetic nephropathy through suppression of inflammatory pathways activated by TNF-${\alpha}$ and AGEs. These findings indicate that KRG has a beneficial effect on pathological conditions associated with diabetic nephropathy.

Keywords

References

  1. Karihaloo A. Anti-fibrosis therapy and diabetic nephropathy. Curr Diab Rep 2012;12:414-422. https://doi.org/10.1007/s11892-012-0290-7
  2. Zhou X, Wang B, Zhu L, Hao S. A novel improved therapy strategy for diabetic nephropathy: targeting AGEs. Organogenesis 2012;8:18-21. https://doi.org/10.4161/org.19332
  3. Yang CY, Wang J, Zhao Y, Shen L, Jiang X, Xie ZG, Liang N, Zhang L, Chen ZH. Anti-diabetic effects of Panax notoginseng saponins and its major anti-hyperglycemic components. J Ethnopharmacol 2010;130:231-236. https://doi.org/10.1016/j.jep.2010.04.039
  4. Yuan HD, Kim SJ, Chung SH. Beneficial effects of IH-901 on glucose and lipid metabolisms via activating adenosine monophosphate-activated protein kinase and phosphatidylinositol-3 kinase pathways. Metabolism 2011;60:43-51. https://doi.org/10.1016/j.metabol.2009.12.024
  5. Lee HJ, Lee YH, Park SK, Kang ES, Kim HJ, Lee YC, Choi CS, Park SE, Ahn CW, Cha BS et al. Korean red ginseng (Panax ginseng) improves insulin sensitivity and attenuates the development of diabetes in Otsuka Long-Evans Tokushima fatty rats. Metabolism 2009;58:1170-1177. https://doi.org/10.1016/j.metabol.2009.03.015
  6. Luo JZ, Luo L. Ginseng on hyperglycemia: effects and mechanisms. Evid Based Complement Alternat Med 2009;6:423-427. https://doi.org/10.1093/ecam/nem178
  7. 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;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  8. Park MJ, Bae CS, Lim SK, Kim DI, Lim JC, Kim JC, Han HJ, Moon JH, Kim KY, Yoon KC et al. Effect of protopanaxadiol derivatives in high glucose-induced fibronectin expression in primary cultured rat mesangial cells: role of mitogen-activated protein kinases and Akt. Arch Pharm Res 2010;33:151-157. https://doi.org/10.1007/s12272-010-2237-3
  9. Rossini AA, Like AA, Chick WL, Appel MC, Cahill GF Jr. Studies of streptozotocin-induced insulitis and diabetes. Proc Natl Acad Sci U S A 1977;74:2485-2489. https://doi.org/10.1073/pnas.74.6.2485
  10. Koschinsky T, He CJ, Mitsuhashi T, Bucala R, Liu C, Buenting C, Heitmann K, Vlassara H. Orally absorbed reactive glycation products (glycotoxins): an environmental risk factor in diabetic nephropathy. Proc Natl Acad Sci U S A 1997;94:6474-6479. https://doi.org/10.1073/pnas.94.12.6474
  11. Pertynska-Marczewska M, Glowacka E, Sobczak M, Cypryk K, Wilczynski J. Glycation endproducts, soluble receptor for advanced glycation endproducts and cytokines in diabetic and non-diabetic pregnancies. Am J Reprod Immunol 2009;61:175-182. https://doi.org/10.1111/j.1600-0897.2008.00679.x
  12. Barlovic DP, Soro-Paavonen A, Jandeleit-Dahm KA. RAGE biology, atherosclerosis and diabetes. Clin Sci (Lond) 2011;121:43-55. https://doi.org/10.1042/CS20100501
  13. Sukkar MB, Ullah MA, Gan WJ, Wark PA, Chung KF, Hughes JM, Armour CL, Phipps S. RAGE: a new frontier in chronic airways disease. Br J Pharmacol 2012; 167:1161-1176. https://doi.org/10.1111/j.1476-5381.2012.01984.x
  14. Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW. Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry 1995;34:3702-3709. https://doi.org/10.1021/bi00011a027
  15. Baker RG, Hayden MS, Ghosh S. NF-${\kappa}B$, inflammation, and metabolic disease. Cell Metab 2011;13:11-22. https://doi.org/10.1016/j.cmet.2010.12.008
  16. Mauer SM, Steffes MW, Ellis EN, Sutherland DE, Brown DM, Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest 1984;74:1143-1155. https://doi.org/10.1172/JCI111523
  17. Adler S. Structure-function relationships associated with extracellular matrix alterations in diabetic glomerulopathy. J Am Soc Nephrol 1994;5:1165-1172.
  18. Schena FP, Gesualdo L. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol 2005;16 Suppl 1:S30-S33. https://doi.org/10.1681/ASN.2004110970
  19. Ichinose K, Kawasaki E, Eguchi K. Recent advancement of understanding pathogenesis of type 1 diabetes and potential relevance to diabetic nephropathy. Am J Nephrol 2007;27:554-564. https://doi.org/10.1159/000107758

Cited by

  1. Advanced Glycation End Products and Diabetic Complications vol.18, pp.1, 2014, https://doi.org/10.4196/kjpp.2014.18.1.1
  2. on Alpha-Adrenergic Receptor of Benign Prostatic Hyperplasia vol.18, pp.4, 2014, https://doi.org/10.5213/inj.2014.18.4.179
  3. Combination with Red ginseng and Polygoni Multiflori ameliorates highfructose diet induced metabolic syndrome vol.16, pp.1, 2016, https://doi.org/10.1186/s12906-016-1063-7
  4. GS-E3D, a new pectin lyase-modified red ginseng extract, inhibited diabetes-related renal dysfunction in streptozotocin-induced diabetic rats vol.17, pp.1, 2017, https://doi.org/10.1186/s12906-017-1925-7
  5. Ginseng for the treatment of diabetes and diabetes-related cardiovascular complications: a discussion of the evidence pp.1205-7541, 2019, https://doi.org/10.1139/cjpp-2018-0440
  6. Ginseng Extract Modified by Pectin Lyase Inhibits Retinal Vascular Injury and Blood-Retinal Barrier Breakage in a Rat Model of Diabetes pp.1557-7600, 2019, https://doi.org/10.1089/jmf.2018.4256
  7. Ginseng Total Saponin Attenuates Podocyte Apoptosis Induced by Diabetic Conditions Through the Recovery of CD2-Associated Protein vol.22, pp.2, 2019, https://doi.org/10.1089/jmf.2017.4139
  8. A High-Fat Diet Increases Oxidative Renal Injury and Protein Glycation in D-Galactose-Induced Aging Rats and Its Prevention by Korea Red Ginseng vol.60, pp.3, 2013, https://doi.org/10.3177/jnsv.60.159
  9. A High-Fat Diet Increases Oxidative Renal Injury and Protein Glycation in D-Galactose-Induced Aging Rats and Its Prevention by Korea Red Ginseng vol.60, pp.3, 2013, https://doi.org/10.3177/jnsv.60.159
  10. A review on the medicinal potential of Panax ginseng saponins in diabetes mellitus vol.5, pp.59, 2013, https://doi.org/10.1039/c5ra05864c
  11. Pectin lyase-modified red ginseng extract exhibits potent anti-glycation effects in vitro and in vivo vol.21, pp.2, 2017, https://doi.org/10.20463/jenb.2017.0011
  12. 홍삼가수분해추출물의 db/db 마우스에서 신장 손상 예방효과 vol.33, pp.4, 2018, https://doi.org/10.6116/kjh.2018.33.4.1
  13. Supplementation with Korean Red Ginseng Improves Current Perception Threshold in Korean Type 2 Diabetes Patients: A Randomized, Double-Blind, Placebo-Controlled Trial vol.2020, pp.None, 2020, https://doi.org/10.1155/2020/5295328
  14. The Ginsenoside Rg1 Rescues Mitochondrial Disorders in Aristolochic Acid-Induced Nephropathic Mice vol.11, pp.10, 2013, https://doi.org/10.3390/life11101018
  15. Panax Ginseng alleviates thioacetamide-induced liver injury in ovariectomized rats: Crosstalk between inflammation and oxidative stress vol.16, pp.11, 2013, https://doi.org/10.1371/journal.pone.0260507
  16. Untargeted metabolomics analysis of the anti-diabetic effect of Red ginseng extract in Type 2 diabetes Mellitus rats based on UHPLC-MS/MS vol.146, pp.None, 2022, https://doi.org/10.1016/j.biopha.2021.112495