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.
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-alpha (TNFalpha). Pre-and post-treatment 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 TNFalpha. No significant improvements were obtained in patients administered placebo.


CONCLUSIONS
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.
Usharani
P
P
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India.
Mateen
A A
AA
Naidu
M U R
MU
Raju
Y S N
YS
Chandra
Naval
N
D000318:Adrenergic beta-Agonists; D000328:Adult; D000420:Albuterol; D000069059:Atorvastatin; D015415:Biomarkers; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003474:Curcumin / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011758:Pyrroles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D000318:Adrenergic beta-Agonists; D000420:Albuterol; D000069059:Atorvastatin; D015415:Biomarkers; D001786:Blood Glucose; D002784:Cholesterol; D003474:Curcumin; D006442:Glycated Hemoglobin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014280:Triglycerides