Skip to main content
SpringerLink
Log in

Effect of NCB-02, Atorvastatin and Placebo on Endothelial Function, Oxidative Stress and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus

A Randomized, Parallel-Group, Placebo-Controlled, 8-Week Study

  • Original Research Article
  • Published:
Drugs in R & D Aims and scope Submit manuscript

Abstract

Background and objective: Hyperglycaemia leads to increased oxidative stress resulting in endothelial dysfunction. ACE inhibitors, antioxidants and HMG-CoA reductase inhibitors (statins) have been shown to improve endothelial function. The aim of this study was to compare the effects of NCB-02 (a standardized preparation of curcuminoids), atorvastatin and placebo on endothelial function and its biomarkers in patients with type 2 diabetes mellitus.

Methods: A total of 72 patients with type 2 diabetes were randomized to receive NCB-02 (two capsules containing curcumin 150 mg twice daily), atorvastatin 10 mg once daily or placebo for 8 weeks. Endothelial function assessment was performed at baseline and post-treatment using digital volume plethysmography (salbutamol [albuterol] challenge test) to measure change in reflective index, an indicator of arterial vascular tone. Blood samples were similarly collected at baseline and post-treatment for estimations of malondialdehyde, endothelin-1 (ET-1), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα). Pre-and posttreatment safety assessments were also conducted. ANOVA and paired t-test evaluations were used for comparison.

Results: A total of 67 patients completed the study. At baseline, there was no significant difference in the various parameters tested. In all three groups, the change in reflective index at baseline was <6% as assessed by the salbutamol challenge test, indicating the presence of endothelial dysfunction. Compared with baseline, there was a significant improvement in endothelial function after treatment with atorvastatin (mean ± SD: −3.63 ± 3.17% vs −8.95 ± 6.80%, respectively) and NCB-02 (−2.69 ± 3.02% vs −8.19 ± 5.73%, respectively). Similarly, patients receiving atorvastatin or NCB-02 showed significant reductions in the levels of malondialdehyde, ET-1, IL-6 and TNFα. No significant improvements were obtained in patients administered placebo.

Conclusion: NCB-02 had a favourable effect, comparable to that of atorvastatin, on endothelial dysfunction in association with reductions in inflammatory cytokines and markers of oxidative stress. Further studies are needed to evaluate the potential long-term effects of NCB-02 and its combination with other herbal antioxidants.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Nishikawa T, Edelstein D, Du XL, et al. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000 Apr 13; 404 (6779): 787–90

    Article  PubMed  CAS  Google Scholar 

  2. Neri S, Signorelli SS, Torrisi B, et al. Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: a single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance, and healthy controls. Clin Ther 2005 Nov; 27 (11): 1764–73

    Article  PubMed  CAS  Google Scholar 

  3. Dogra G, Rich L, Stanton K, et al. Endothelium-dependent and independent vasodilation studies at normoglycaemia in type I diabetes mellitus with and without microalbuminuria. Diabeto logia 2001 May; 44 (5): 593–601

    Article  CAS  Google Scholar 

  4. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813–20

    Article  PubMed  CAS  Google Scholar 

  5. Esposito K, Nappo F, Giugliano F, et al. Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects. Am J Clin Nutr 2003 Jan; 77 (1): 139–43

    PubMed  CAS  Google Scholar 

  6. Cuevas AM, Germain AM. Diet and endothelial function. Biol Res 2004; 37 (2): 225–30

    Article  PubMed  Google Scholar 

  7. Vlachopoulos C, Aznaouridis K, Alexopoulos N, et al. Effect of dark chocolate on arterial function in healthy individuals. Am J Hypertens 2005 Jun; 18 (6): 785–91

    Article  PubMed  CAS  Google Scholar 

  8. Duffy SJ, Keaney Jr JF, Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation 2001 Jul 10; 104 (2): 151–6

    Article  PubMed  CAS  Google Scholar 

  9. Ramaswami G, Chai H, Yao Q, et al. Curcumin blocks homocysteine-induced endothelial dysfunction in porcine coronary arteries. J Vasc Surg 2004 Dec; 40 (6): 1216–22

    Article  PubMed  Google Scholar 

  10. Balasubramanyam M, Koteswari AA, Kumar RS, et al. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications. J Biosci 2003 Dec; 28 (6): 715–21

    Article  PubMed  CAS  Google Scholar 

  11. Tousoulis D, Antoniades C, Vassiliadou C, et al. Effects of combined administration of low dose atorvastatin and vitamin E on inflammatory markers and endothelial function in patients with heart failure. Eur J Heart Fail 2005 Dec; 7 (7): 1126–32

    Article  PubMed  CAS  Google Scholar 

  12. Mozaffarian D, Minami E, Letterer RA, et al. The effects of atorvastatin (10 mg) on systemic inflammation in heart failure. Am J Cardiol 2005 Dec 15; 96 (12): 1699–704

    Article  PubMed  CAS  Google Scholar 

  13. Mohan IK, Kumar KV, Naidu MUR, et al. Protective effect of Cardipro against doxorubicin induced cardiotoxicity in mice. Phytomedicine 2006; 13: 222–9

    Article  PubMed  CAS  Google Scholar 

  14. Chowienczyk PJ, Kelly RP, MacCallum H, et al. Photoplethys-mographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus. J Am Coll Cardiol 1999 Dec; 34 (7): 2007–14

    Article  PubMed  CAS  Google Scholar 

  15. Naidu MUR, Yashmaina S, Usharani P, et al. Comparison of two β2 adrenoceptor agonists by different routes of administration to assess human endothelial function. Indian J Pharmacol 2007; 39 (3): 168–9

    Article  Google Scholar 

  16. Millasseau S, Kelly R, Ritter J, et al. Determination of age related increases in large artery stiffness by digital pulse contour analysis. Clin Sci (Lond) 2002; 103: 371–7

    CAS  Google Scholar 

  17. Tantikosoom W, Thinkhamrop B, Kiatchusakul S, et al. Randomized trial of atorvastatin in improving endothelial function in diabetics without prior coronary disease and having average cholesterol level. J Med Assoc Thai 2005 Mar; 88 (3): 399–406

    PubMed  Google Scholar 

  18. Schalkwijk CG, Stehouwer CDA. Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci (Lond) 2005: 109: 143–59

    Article  CAS  Google Scholar 

  19. Economides PA, Caselli A, Tiani E, et al. The effects of atorvastatin on endothelial function in diabetic patients and subjects at risk for type 2 diabetes. J Clin Endocrinol Metab 2004 Feb; 89 (2): 740–7

    Article  PubMed  CAS  Google Scholar 

  20. Ceriello A, Assaloni R, Da Ros R, et al. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation 2005 May 17; 111 (19): 2518–24

    Article  PubMed  CAS  Google Scholar 

  21. Lam HC, Chu CH, Wei MC, et al. The effects of different doses of atorvastatin on plasma endothelin-1 levels in type 2 diabetic patients with dyslipidemia. Exp Biol Med (Maywood) 2006 Jun; 231 (6): 1010–5

    CAS  Google Scholar 

  22. Save V, Patil N, Moulik N, et al. Effect of atorvastatin on type 2 diabetic dyslipidemia. J Cardiovasc Pharmacol Ther 2006 Dec; 11 (4): 262–70

    Article  PubMed  CAS  Google Scholar 

  23. Mason RP, Walter MF, Jacob RF. Effects of HMG-CoA reductase inhibitors on endothelial function: role of microdomains and oxidative stress. Circulation 2004 Jun 1; 109 (21 Suppl. 1): II34–41

    PubMed  Google Scholar 

  24. Ceriello A. New insights on oxidative stress and diabetic complications may lead to a ‘causal’ antioxidant therapy. Diabetes Care 2003 May; 26 (5): 1589–96

    Article  PubMed  CAS  Google Scholar 

  25. Joe B, Lokesh BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages. Biochim Biophys Acta 1994 Nov 10; 1224 (2): 255–63

    Article  PubMed  CAS  Google Scholar 

  26. Sreejayan N, Rao MN. Free radical scavenging activity of curcuminoids. Arzneimittelforschung 1996 Feb; 46 (2): 169–71

    PubMed  CAS  Google Scholar 

  27. Durgaprasad S, Pai CG, Vasanthkumar, et al. A pilot study of the antioxidant effect of curcumin in tropical pancreatitis. Indian J Med Res 2005 Oct; 122 (4): 315–8

    PubMed  CAS  Google Scholar 

  28. Soni KB, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol 1992 Oct; 36 (4): 273–5

    PubMed  CAS  Google Scholar 

  29. Baum L, Cheung SK, Mok VC, et al. Curcumin effects on blood lipid profile in a 6-month human study. Pharmacol Res 2007 Dec; 56 (6): 509–14

    Article  PubMed  CAS  Google Scholar 

  30. Brennan P, O’Neill LA. Inhibition of nuclear factor kappaB by direct modification in whole cells: mechanism of action of nordihydroguairartic acid, curcumin and thiol modifiers. Biochem Pharmacol 1998; 55 (7): 965–73

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr S.K. Mithra, Executive Director R&D, Himalaya Healthcare Pvt Ltd, Bangalore, India for providing the study medication and the research grant for the conduct of the study. The authors would also like to thank Ms P. Sridevi of Sristek Consultancy for performing the statistical analysis. The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500 082, Andhra Pradesh, India

    P. Usharani, A. A. Mateen & M. U. R. Naidu

  2. Department of General Medicine, Nizam’s Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India

    Y. S. N. Raju & Naval Chandra

Authors
  1. P. Usharani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. A. Mateen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. U. R. Naidu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. S. N. Raju
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Naval Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. Usharani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Usharani, P., Mateen, A.A., Naidu, M.U.R. et al. Effect of NCB-02, Atorvastatin and Placebo on Endothelial Function, Oxidative Stress and Inflammatory Markers in Patients with Type 2 Diabetes Mellitus. Drugs R D 9, 243–250 (2008). https://doi.org/10.2165/00126839-200809040-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00126839-200809040-00004

Keywords

Search

Navigation