Skip to main content

Advertisement

SpringerLink
Log in

Pioglitazone, extract of compound Danshen dripping pill, and quercetin ameliorate diabetic nephropathy in diabetic rats

  • Original Article
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background: Oxidative stress appears to play a role in the pathogenesis of diabetes mellitus (DM), and disruption of the ubiquitin-proteasome system may underlie these pathological changes. We tested the effect of pioglitazone (PIO), an extract of Danshen dripping pill (DSP), and quercetin (QUE) on the pathogenesis of DM in a rat model. Methods: Male Sprague Dawley rats were maintained in a normal control (NC) group or given a modified diet and streptozotocin (STZ) to induce DM. After STZ treatment, rats were given intragastric placebo, PIO, DSP, or QUE for 8 weeks. At the end of the treatment period, serum and urine chemistry, renal hypertrophy, renal histopathology, and renal expression of ubiquitin and nuclear factor (NF)-κB p65 were analyzed. Results: DM rats had altered body and kidney weight, altered serum and urine chemistry, increased accumulation of glomerular extracellular matrix (ECM), and increased renal expression of ubiquitin and NF-κB p65, indicating successful establishment of our DM model. Treatment with PIO, DSP, or QUE significantly ameliorated these pathological changes, although treated rats still had some symptoms of DM. Conclusion: DM rats have increased expression of ubiquitin and NF-κB p65 in their renal tubules and glomeruli. PIO, DSP, and QUE ameliorated the pathological changes associated with DM and also reduced the renal expression of ubiquitin and NF-κB p65. These agents may provide protection from renal pathology associated with DM due to their anti-oxidant effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Masoudi FA, Inzucchi SE. Diabetes mellitus and heart failure: epidemiology, mechanisms, and pharmacotherapy. Am J Cardiol 2007, 99: 113B–32B.

    Article  CAS  PubMed  Google Scholar 

  2. Chan JC, Malik V, Jia W, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009, 301: 2129–40.

    Article  CAS  PubMed  Google Scholar 

  3. Marcovecchio ML, Lucantoni M, Chiarelli F. Role of chronic and acute hyperglycemia in the development of diabetes complications. Diabetes Technol Ther 2011, 13: 389–94.

    Article  CAS  PubMed  Google Scholar 

  4. Najafian B, Alpers CE, Fogo AB. Pathology of human diabetic nephropathy. Contrib Nephrol 2011, 170: 36–47.

    Article  PubMed  Google Scholar 

  5. Navarro-González JF, Mora-Fernández C, Muros de Fuentes M, García-Pérez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 2011, 7: 327–40.

    Article  PubMed  Google Scholar 

  6. Hanif K, Bid HK, Konwar R. Reinventing the ACE inhibitors: some old and new implications of ACE inhibition. Hypertens Res 2010, 33: 11–21.

    Article  CAS  PubMed  Google Scholar 

  7. Shah P, Mudaliar S. Pioglitazone: side effect and safety profile. Expert Opin Drug Saf 2010, 9: 347–54.

    Article  CAS  PubMed  Google Scholar 

  8. Stewart LK, Soileau JL, Ribnicky D, et al. Quercetin transiently increases energy expenditure but persistently decreases circulating markers of inflammation in C57BL/6J mice fed a high-fat diet. Metabolism 2008, 57: S39–46.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Xie W, Du L. Diabetes is an inflammatory disease: evidence from traditional Chinese medicines. Diabetes Obes Metab 2011, 13: 289–301.

    Article  CAS  PubMed  Google Scholar 

  10. Tao W, Deqin Z, Yuhong L, et al. Regulation effects on abnormal glucose and lipid metabolism of TZQ-F, a new kind of Traditional Chinese Medicine. J Ethnopharmacol 2010, 128: 575–82.

    Article  PubMed  Google Scholar 

  11. Liu CL, Xie LX, Li M, Durairajan SS, Goto S, Huang JD. Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling. PLoS One 2007, 2: e1321.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Zhao Y, Krishnamurthy B, Mollah ZU, Kay TW, Thomas HE. NF-κB in type 1 diabetes. Inflamm Allergy Drug Targets 2011, 10: 208–17.

    Article  CAS  PubMed  Google Scholar 

  13. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005, 54: 1615–25.

    Article  CAS  PubMed  Google Scholar 

  14. Grune T, Reinheckel T, Davies KJ. Degradation of oxidized proteins in mammalian cells. FASEB J 1997, 11: 526–34.

    CAS  PubMed  Google Scholar 

  15. Donaldson KM, Li W, Ching KA, Batalov S, Tsai CC, Joazeiro CA. Ubiquitin mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci USA 2003, 100: 8892–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Goellner GM, Rechsteiner M. Are Huntington’s and polyglutamine based ataxias proteasome storage diseases? Int J Biochem Cell Biol 2003, 35: 562–71.

    Article  CAS  PubMed  Google Scholar 

  17. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001, 292: 1552–5.

    Article  CAS  PubMed  Google Scholar 

  18. Marfella R, D’Amico M, Di Filippo C, et al. The possible role of the ubiquitin proteasome system in the development of atherosclerosis in diabetes. Cardiovasc Diabetol 2007, 6: 35.

    Article  PubMed Central  PubMed  Google Scholar 

  19. Susztak K, Raff AC, Schiffer M, Böttinger EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 2006, 55: 225–33.

    Article  CAS  PubMed  Google Scholar 

  20. Kumar D, Zimpelmann J, Robertson S, Burns KD. Tubular and interstitial cell in the steptozotocin diabetic rat kidney. Nephron Exp Nephrol 2004, 96: 77–88.

    Article  Google Scholar 

  21. Derosa G. Efficacy and tolerability of pioglitazone in patients with type 2 diabetes mellitus: comparison with other oral antihyperglycaemic agents. Drugs 2010, 70: 1945–61.

    Article  CAS  PubMed  Google Scholar 

  22. Moraes LA, Piqueras L, Bishop D. Peroxisome proliferator activated receptors and inflammation. Pharmacol Ther 2005, 14: 2–4.

    Google Scholar 

  23. Marfella R, D’Amico M, Esposito K, et al. The Ubiquitin-proteasome system and inflammatory activity in diabetic atherosclerotic plaques. Diabetes 2006, 55: 622–32.

    Article  CAS  PubMed  Google Scholar 

  24. Tian JY, Chen JZ, Gu Y, Xi SF. Effect of fufang danshen diwan on blood lipid level and carotid atherosclerosis plaque in rabbits. Chin J Clin Rehabil 2004, 22: 437.

    Google Scholar 

  25. Xu JL, Wang XM, Wang DX. The protection of composite salviae dropping pills against HUVECs injury induced by H2O2. Chin J Pathophysiol 2006, 22: 929.

    Google Scholar 

  26. Chen P, Xu XJ, Shi DH. The influence of compound Danshen dripping pill on insulin resistance in rats. Chin J Integr Med Cardio/Cerebrovasc Dis 2008, 6: 33–6.

    Google Scholar 

  27. Xu P, Xu XJ, Shi DH. Anti-proliferative effects of compound Danshen dripping pill on rabbit aortic smooth muscle cells during the insulin resistance state. Chin J Integr Tradit West Med Intens Crit Care 2007, 14: 313–6.

    Google Scholar 

  28. Moon SK, Cho GO, Jung SY, et al. Quercetin exerts multiple inhibitory effects on vascular smooth muscle cells: role of ERK1/2, cell-cycle regulation, and matrix metalloproteinase-9. Biochem Biophys Res Commun 2003, 301: 1069–78.

    Article  CAS  PubMed  Google Scholar 

  29. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol Toxicol Pharmacol 2003, 135: 357–64.

    Article  Google Scholar 

  30. Coskun O, Kanter M, Korkmaz A, Oter S. Quercetin, a flavonoid antioxidant, prevents and protects streptozocin induced oxidative stress and β-cells damage in rat pancreas. Pharmacol Res 2005, 51: 117–23.

    Article  CAS  PubMed  Google Scholar 

  31. Kamada C, da Silva EL, Ohnishi-Kameyama M, Moon JH, Terao J. Attenuation of lipid peroxidation and hyperlipidemia by quercetin glucoside in the aorta of high cholesteol-fed rabbit. Free Radic Res 2005, 39: 185–94.

    Article  CAS  PubMed  Google Scholar 

  32. Xu XJ, Zhang LQ, Wang QB, Feng XG, Zheng ZY, Chen P. Protective effect of quercetin on kidneys in diabetic rats. Chin J Endocrinol Metab 2001, 17: 316–9.

    CAS  Google Scholar 

  33. Xu XJ, Wu YS, Feng XG, et al. Effects of quercetin on TGF-β1 in diabetic rat kidney. Chin J Diabetes 2001, 9: 44–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Endocrinology, Fuzhou General Hospital of Nanjing Military Command, No. 156, Xi’er huan North Road, Fuzhou, Fujian, 350025, China

    P. Chen, Q. Zheng, W. Chen, Y. Wang & X. Xu MD

  2. Armed Police Corps Hospital of Fujian, Fuzhou, Fujian, China

    J. Chen

Authors
  1. P. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Q. Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. W. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X. Xu MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X. Xu MD.

Additional information

P. Chen and J. Chen contributed to this manuscript equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, P., Chen, J., Zheng, Q. et al. Pioglitazone, extract of compound Danshen dripping pill, and quercetin ameliorate diabetic nephropathy in diabetic rats. J Endocrinol Invest 36, 422–427 (2013). https://doi.org/10.3275/8763

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3275/8763

Key-words

Search

Navigation