Drugs R D 2008; 9 (4): 243-250

ORIGINAL RESEARCH ARTICLE 1174-5886/08/0004-0243/$48.00/0

© 2008 Adis Data Information BV. All rights reserved.

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
P. Usharani,1 A.A. Mateen,1 M.U.R. Naidu,1 Y.S.N. Raju2 and Naval Chandra2
1 Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical
Sciences, Hyderabad, Andhra Pradesh, India
2 Department of General Medicine, Nizam’s Institute of Medical Sciences, Hyderabad, Andhra
Pradesh, India

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 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 treat-
ment with atorvastatin (mean ± SD: –3.63 ± 3.17% vs –8.95 ± 6.80%, respective-
ly) 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
244 Usharani et al.

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 cyto-
kines 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.

Background foods and beverages rich in flavonoids is associated

Macro- and microvascular diseases are the prin-
cipal contributors to morbidity and mortality in pa-
tients with type 1 and type 2 diabetes mellitus. In
both type 1 and type 2 diabetes there is a loss of the
modulatory role of the endothelium, which may be a
critical and initiating factor in the development of
diabetic vascular disease. The vascular endothelium
is particularly vulnerable to hyperglycaemia-in-
duced damage as, unlike many other cell types,
endothelial cells cannot downregulate glucose trans-
port.[1] The relationship between early endothelial
damage, glycaemic control, disorders of lipid meta-
bolism, oxidative stress, age and coagulative
haemostatic disorders has long been recognized.[2]
In diabetes, hyperglycaemia induces oxidative cellu-
lar changes in all elements of the vascular wall, with
endothelial dysfunction occurring early in the time
course of the metabolic disorder.[3] In addition to
endothelial damage, oxidative stress appears to be
involved in all of the major pathogenic mechanisms
leading to diabetic complications. In an attempt to
build a unifying theory of the pathogenesis of diabe-
tes and diabetic complications, researchers have
identified oxidative stress as the common factor in
most of the known biochemical mechanisms of this
disease.[4]
Clinical studies have shown a beneficial role for
antioxidants on endothelial function.[5] Studies have
shown that the water-soluble antioxidant ascorbic
acid (vitamin C) and the lipid-soluble antioxidants
tocopherol (vitamin E) and probucol have beneficial
effects on endothelial function by decreasing
downregulation of endothelial nitric oxide synthase
expression.[6] In addition, several epidemiological
studies have suggested that regular consumption of
with a decreased risk of cardiovascular mortality.[7]
One proposed mechanism for the benefit of dietary
flavonoids is their antioxidant properties. These
polyphenols are effective scavengers of reactive ox-
ygen species and can inhibit lipid peroxidation
through chelation of transition metal ions or their
action as chain-breaking antioxidants.[8]
The significance of Curcuma longa (turmeric) in
health and nutrition has changed significantly since
the discovery of antioxidant properties for naturally
occurring phenolic compounds. The dried rhizome
of C. longa is a rich source of beneficial phenolic
compounds – the curcuminoids. Three main
curcuminoids, namely curcumin, demethoxy curcu-
min and bisdemethoxy curcumin, have been isolated
from turmeric. Experimental studies have shown
that curcuminoids have significant antioxidant ac-
tivity and inhibit cellular reactive oxygen genera-
tion.[9-12] Furthermore, it has been suggested that
curcumin may have a potentially beneficial role in
the treatment of diabetes and its related vascular
complications.[9,10] In view of this perspective, the
present study was aimed to evaluate the effects of
NCB-02 (standardized preparation of curcuminoids)
on endothelial function and its biomarkers in pa-
tients with type 2 diabetes.
Subjects and Methods
The study was conducted between October 2005
and January 2007. All subjects seen consecutively at
our institution who were willing to participate in the
study and fulfilled the inclusion/exclusion criteria
were enrolled in the study. Inclusion criteria were
age 21–80 years, fasting plasma glucose of
≥130 mg/dL, a glycosylated haemoglobin (HbA1c)

© 2008 Adis Data Information BV. All rights reserved. Drugs R D 2008; 9 (4)
Endothelial Dysfunction and Type 2 Diabetes Mellitus
range of between 7% and 11%, and taking stable
antihyperglycaemic medications for a 2-month
period. To avoid confounding factors known to af-
fect endothelial function, the following exclusion
criteria were applied: severe uncontrolled hypergly-
caemia (HbA1c >11%), treatment with lipid-lower-
ing drugs during the previous 3 months, smoking,
chronic alcoholism, uncontrolled hypertension, car-
diac arrhythmia, congestive heart failure, evidence
of hepatic and renal impairment or any other serious
chronic disease requiring active treatment, and treat-
ment with any other herbal supplements.
The study was approved by the Institutional Eth-
ics Committee of Nizam’s Institute of Medical Sci-
ences, Hyderabad, Andhra Pradesh, India. All sub-
jects provided written informed consent prior to
entry into the study.
Study Design
The study was a randomized, parallel group, pla-
cebo-controlled, 8-week study. Subjects were ran-
domized to receive either NCB-02 (a newly formu-
lated, standardized preparation of C3 curcuminoids
[curcumin, demethoxy curcumin and bisdemethoxy
curcumin] in a capsule containing curcumin
150 mg) two capsules twice daily, atorvastatin
10 mg tablets once daily (dosage selected on the
basis of earlier published reports[11,12]), or placebo
one capsule twice daily.
Clinical and Laboratory Assessments
All subjects underwent complete physical exam-
ination, laboratory evaluation and endothelial func-
tion assessment at baseline and at the end of treat-
ment. All parameters were assessed in the morning
after an overnight fast and 12 hours after the last
dose of medication. Complete physical examination
included weight, height and blood pressure mea-
surement. Blood was drawn for determination of
haemoglobin level, HbA1c, urea and creatinine
levels, liver function, biomarker levels (endothe-
lin-1 [ET-1], tumour necrosis factor-α [TNFα],
interleukin-6 [IL-6] and malondialdehyde [a marker
of oxidative stress]) and lipid profile (total choles-
© 2008 Adis Data Information BV. All rights reserved.
245
terol, high-density lipoprotein-cholesterol [HDL-C],
triglycerides and low-density lipoprotein-cholester-
ol [LDL-C]). Plasma glucose, total serum cholester-
ol, serum triglycerides, HDL-C, liver function tests,
blood urea nitrogen, serum creatinine and HbA1c
were measured using appropriate standard tech-
niques. Malondialdehyde was estimated spec-
trophotometrically using the thiobarbituric acid re-
active substances method as per the procedure de-
scribed by Mohan et al.[13] ET-1, TNFα and IL-6
were measured in plasma by the ELISA method
(Biomedica Gruppe, Vienna, Austria; Bender Med-
Systems, Vienna, Austria)
Any adverse events that were reported were re-
corded on the case report form.
Assessment of Endothelial Function
A salbutamol (albuterol) challenge test employ-
ing digital volume plethysmography was used to
assess endothelial function as reported by
Chowienczyk et al.[14] and Naidu et al.[15] In brief,
patients were examined in the supine position after
5 minutes’ rest. A digital volume pulse (DVP) was
obtained using a photoplethysmograph (Pulse Trace
PCA2, PT2000, Micro Medical, Gallingham, Kent,
UK) transmitting infrared light at 940 nm, placed on
the index finger of right hand. The signal from the
plethysmograph was digitized using a 12-bit ana-
logue to digital converter with a sampling frequency
of 100 Hz. DVP waveforms were recorded over a
10-second period and the height of the late systolic/
early diastolic portion of the DVP was expressed as
a percentage of the amplitude of the DVP to yield
the reflection index (RI), as per the procedure de-
scribed in detail by Millasseau et al.[16] After DVP
recordings had been taken, three measurements of
RI were calculated and the mean value was deter-
mined. Patients were then administered 400 μg of
salbutamol by inhalation. After 15 minutes three
measurements of RI were obtained again and the
difference in mean RI before and after the adminis-
tration of salbutamol was used for assessing endo-
thelial function.
Drugs R D 2008; 9 (4)
246 Usharani et al.

Table I. Demographic details and baseline biochemical characteristics of the study groupsa,b
Variable Placebo Atorvastatin NCB-02
Total no. 21 23 23
Age (y) 49.75 ± 8.18 50.47 ± 10.35 55.52 ± 10.76
Sex (M/F)c 11/10 12/11 12/11
Weight (kg) 61.51 ± 8.63 64.64 ± 9.27 63.64 ± 10.77
BMI (kg/m2) 23.98 ± 2.35 25.03 ± 1.83 24.66 ± 2.42
SBP (mmHg) 126.38 ± 15.43 127.73 ± 11.96 130.43 ± 18.59
DBP (mmHg) 80.71 ± 7.48 80.95 ± 7.93 81.82 ± 10.02
Fasting glucose (mg/dL) 161.19 ± 19.97 161.21 ± 19.74 155.04 ± 17.94
HbA1c (%) 7.82 ± 0.57 8.30 ± 0.86 8.04 ± 0.85
Total cholesterol (mg/dL) 196.95 ± 35.72 196.78 ± 35.28 195.0 ± 41.16
HDL-C (mg/dL) 36.38 ± 7.67 36.82 ± 5.45 38.78 ± 7.69
LDL-C (mg/dL) 125.29 ± 34.94 123.50 ± 38.73 120.35 ± 42.13
Triglycerides (mg/dL) 170.14 ± 47.54 182.26 ± 43.85 176.39 ± 27.61
Antihyperglycaemic therapyd
metformin 08 (38) 06 (26) 08 (35)
metformin + sulfonylurea drugse 13 (62) 17 (74) 15 (65)
a Data for 67 pts who completed the study.
b Except where specified otherwise, values are expressed as mean ± SD.
c No. of pts.
d No. (%) of pts.
e Sulfonylurea drugs include glimepiride, glipizide and glibenclamide (glyburide).
BMI = body mass index; DBP = diastolic blood pressure; F = female; HbA1c = glycosylated haemoglobin; HDL-C = high-density lipoprotein-
cholesterol; LDL-C = low-density lipoprotein-cholesterol; M = male; pts = patients; SBP = systolic blood pressure.

Statistical Analysis tory cytokines and malondialdehyde were similar in

Data are expressed as mean ± SD. Between-
group analysis was performed using ANOVA fol-
lowed by Tukey’s multiple comparison test; within-
group analysis was performed using the paired t-
test. A p-value <0.05 was considered to be statisti-
cally significant. All statistical analysis was per-
formed using the Graphpad Prism® software version
4 (Graphpad Software Inc., San Diego, CA, USA).
Results
A total of 72 subjects were enrolled into the
study, of whom 67 completed the treatment course.
Three subjects were lost to follow-up; two other
subjects relocated and hence were unable to contin-
ue the study. Detailed demographic and biochemical
characteristics of the three study groups are shown
in table I. There was no significant difference be-
tween treatment groups in sex, age, body mass in-
dex, blood pressure, fasting blood glucose, HbA1c or
lipid profile. At baseline, serum levels of inflamma-
all three groups.
The effects of treatment with NCB-02, atorvasta-
tin and placebo are summarized in table II and table
III. Compared with baseline, treatment with
NCB-02 non-significantly reduced total cholesterol
(195.0 ± 41.2 to 185.3 ± 34.4 mg/dL), LDL-C
(120.4 ± 42.1 to 111.3 ± 37.7 mg/dL) and tri-
glycerides (176.4 ± 27.6 to 165.3 ± 25.8 mg/dL).
NCB-02 also improved endothelial function, as indi-
cated by a significant decrease in RI post-salbutamol
(–2.69 ± 3.02% pretreatment vs –8.19 ± 5.73% post-
treatment). There were also significant reductions in
the levels of all biomarkers in patients treated with
NCB-02: ET-1 was 1.38 ± 0.51 at baseline vs
0.67 ± 0.13 after 8 weeks’ treatment, IL-6
4.53 ± 0.88 vs 1.83 ± 0.67, respectively, TNFα
4.10 ± 2.10 vs 1.45 ± 1.20, respectively, and
malondialdehyde 4.09 ± 0.70 vs 2.48 ± 0.30, respec-
tively. Compared with baseline, atorvastatin signifi-
cantly reduced total cholesterol (196.8 ± 35.3 to

© 2008 Adis Data Information BV. All rights reserved. Drugs R D 2008; 9 (4)
Endothelial Dysfunction and Type 2 Diabetes Mellitus 247

158.7 ± 23.7 mg/dL), LDL-C (123.5 ± 38.7 to

88.8 ± 26.0 mg/dL) and triglycerides (182.3 ± 43.9

111.34 ± 37.65

165.26 ± 25.78
150.17 ± 18.84

185.34 ± 34.35
post-treatment

39.91 ± 6.08
to 142.7 ± 17.7 mg/dL). Atorvastatin also improved
8.03 ± 0.76

HbA1c = glycosylated haemoglobin; HDL-C = high-density lipoprotein-cholesterol; LDL-C = low-density lipoprotein-cholesterol. * p < 0.001 compared with baseline.
endothelial function, as shown by a statistically sig-
nificant decrease in RI post-salbutamol (–3.63 ±
3.17% pretreatment vs –8.95 ± 6.80% post-treat-
ment). Similarly, there was a decrease in all bi-
120.35 ± 42.13
omarker levels: ET-1 was 1.31 ± 0.33 pg/mL at
176.39 ± 27.61
155.04 ± 17.94

baseline vs 0.65 ± 0.11 pg/mL after 8 weeks of

195.0 ± 41.16

38.78 ± 7.69
pretreatment

8.04 ± 0.85

atorvastatin treatment, IL-6 4.33 ± 0.89 vs

NCB-02

1.62 ± 0.43 pg/mL, respectively, TNFα 3.57 ± 1.10

vs 0.75 ± 0.63 pg/mL, respectively, and malondi-
aldehyde 3.46 ± 0.51 vs 2.16 ± 0.17 pg/mL, respec-
tively.
Table II. Changes (mean ± SD) in biochemical parameters after 8 weeks’ treatment with placebo, atorvastatin and NCB-02

There were no serious adverse events in the

142.73 ± 17.67*
158.69 ± 23.69*
157.73 ± 16.51
post-treatment

88.8 ± 26.05*
38.78 ± 6.34

study; however, two subjects complained of mild

8.29 ± 0.81

diarrhoea in the NCB-02 group. No subjects were

withdrawn or left the study because of these adverse
events.

Discussion
123.50 ± 38.73

182.26 ± 43.85
161.21 ± 19.74

196.78 ± 35.28

36.82 ± 5.45
pretreatment
Atorvastatin

8.30 ± 0.86

In this study, we evaluated the effects of NCB-02

600 mg/day, a potent herbal antioxidant, atorvasta-
tin 10 mg/day, a cholesterol-lowering drug, and
placebo administered for 8 weeks on endothelial
function in patients with type 2 diabetes. NCB-02
exerted beneficial effects on endothelial function
122.18 ± 35.56

168.14 ± 47.10
158.14 ± 17.38

198.76 ± 35.09
post-treatment

accompanied by a statistically significant decrease

37.04 ± 5.92
7.80 ± 0.62

in the levels of inflammatory cytokines and

malondialdehyde. Furthermore, there was an appar-
ent, albeit not statistically significant, reduction in
the levels of total cholesterol and triglycerides.
Atorvastatin also improved endothelial function and
reduced the levels of total cholesterol, triglycerides,
125.29 ± 34.94

170.14 ± 47.54
161.19 ± 19.97

196.95 ± 35.72

36.38 ± 7.67
pretreatment

LDL-C and inflammatory cytokines. Placebo had no

7.82 ± 0.57
Placebo

significant effect on endothelial function or other

evaluated parameters.
Patients with diabetes have vascular complica-
tions and endothelial dysfunction is one of the early
Total cholesterol (mg/dL)
Fasting glucose (mg/dL)

prognostic markers of atheroscelerosis.[17] Studies

Triglycerides (mg/dL)

have reported that endothelial dysfunction occurs in

HDL-C (mg/dL)

LDL-C (mg/dL)

patients with diabetes much earlier than clinical

HbA1c (%)
Parameter

manifestations of diabetic vascular complica-

tions.[18] In our study, there was a post-salbutamol
decrease in RI of <6% at baseline, indicating pres-

© 2008 Adis Data Information BV. All rights reserved. Drugs R D 2008; 9 (4)
248 Usharani et al.

ence of endothelial dysfunction. Some studies have

ET-1 = endothelin-1; IL-6 = interleukin-6; MDA = malondialdehyde; RI = reflection index; TNFα = tumour necrosis factor-α. * p < 0.01, ** p < 0.001 compared with baseline.
suggested that oxidative stress is one of the mechan-
post-treatment
–8.19 ± 5.73*

2.48 ± 0.30**
isms involved in endothelial dysfunction and have

1.45 ± 1.20*
0.67 ± 0.13*

1.83 ± 0.67*
reported an increase in levels of inflammatory cyto-
Table III. Changes (mean ± SD) in endothelial function and biomarkers of endothelial function after 8 weeks’ treatment with placebo, atorvastatin and NCB-02

kines in patients with diabetes.[19,20] Similarly, in our

study we found that levels of all inflammatory cyto-
kines and malondialdehyde were elevated in all
study groups.
The effects of atorvastatin on lipid levels in pa-
–2.69 ± 3.02
pretreatment

1.38 ± 0.51

4.53 ± 0.88

4.10 ± 2.10

4.09 ± 0.70
tients with type 2 diabetes are well documented.
NCB-02

Studies have shown that atorvastatin reduces total

cholesterol, total triglycerides and LDL-C, while
increasing levels of HDL-C.[21,22] Our results are in
accordance with these findings. Atorvastatin has
also been shown to reduce levels of TNFα, IL-6,
post-treatment

ET-1 and malondialdehyde in patients with type 2

–8.95 ± 6.80*

0.75 ± 0.63**

2.16 ± 0.17*
0.65 ± 0.11*

1.62 ±.0.43*

diabetes.[19,23,24] In our study, treatment with atorva-

statin significantly reduced elevated levels of in-
flammatory markers in patients with type 2 diabetes,
which again is in accordance with these earlier pub-
lished reports. Furthermore, it has been suggested
that atorvastatin protects endothelial function and
–3.63 ± 3.17
pretreatment
Atorvastatin

reduces inflammation in patients with diabetes and

1.31 ± 0.33

4.33 ± 0.89

3.57 ± 1.10

3.46 ± 0.51

these effects appear to be mediated through the

drug’s intracellular antioxidant activity.[23] The re-
sults of our study further strengthen this observa-
tion, as there was an improvement in endothelial
function together with a reduction in the levels of all
inflammatory markers with atorvastatin treatment.
post-treatment
–3.42 ± 5.15

4.04 ± 1.19
1.35 ± 0.65

3.57 ± 2.21

3.96 ± 1.37

Curcumin is known to have potent antioxidant

and anti-inflammatory activity.[9-11] An early
preclinical study in rat peritoneal macrophages
grown in vitro demonstrated impairment of reactive
oxygen species generation by 10 μmol/L of curcu-
min.[25] Curcumin has also been shown to scavenge
superoxide anion radicals and hydroxyl radicals.[26]
–4.18 ± 4.36
pretreatment

3.88 ± 1.51
1.21 ± 0.49

4.30 ± 2.38

3.60 ± 1.57

The antioxidant properties of curcumin have also

Placebo

been demonstrated in a recent pilot study in patients

with chronic, nonalcoholic, tropical pancreatitis.[27]
In this study, 20 patients were randomized to receive
salbutamol challenge
Change in RI post-

either oral curcumin 500 mg in combination with

MDA (nmol/mL)
TNFα (pg/mL)

piperine 5 mg or placebo for up to 6 weeks. The

ET-1 (pg/mL)

IL-6 (pg/mL)
Parameter

investigators evaluated erythrocyte levels of

malondialdehyde and glutathione as well as the ef-
(%)

fects of treatment on clinical pain patterns using a

© 2008 Adis Data Information BV. All rights reserved. Drugs R D 2008; 9 (4)
Endothelial Dysfunction and Type 2 Diabetes Mellitus
visual analogue scale for assessment of abdominal
pain. The results showed that patients treated with
curcumin and piperine had significantly lower levels
of malondialdehyde than the placebo group. Eryth-
rocyte glutathione levels remained unaltered and
there was no change in pain severity.
Soni and Kuttan[28] have shown that treatment
with curcumin reduces lipid levels; however, in our
study, NCB-02 did not significantly decrease total
cholesterol, triglyceride and LDL-C levels, nor sig-
nificantly increase HDL-C levels. Similarly in a
recent, randomized, double-blind, placebo-control-
led trial, Baum et al.[29] reported that curcumin at
dosages of 1 g/day and 4 g/day for 6 months did not
produce any significant changes in lipid levels.
In in vitro studies, curcumin has been shown to
reduce levels of inflammatory cytokines. In one
such study,[30] curcumin was found to inhibit IL-1
and TNFα. In another study, curcumin blocked
homocysteine-induced endothelial dysfunction in
porcine coronary arteries.[9] In the present study,
NCB-02 had beneficial effects on endothelial func-
tion in patients with diabetes, as indicated by a
greater percentage decrease in RI in patients receiv-
ing NCB-02 compared with placebo. There were
also significant reductions in levels of IL-6, TNFα
and ET-1. NCB-02 also markedly decreased elevat-
ed levels of malondialdehyde in patients with diabe-
tes in this study. To our knowledge, this is the first
study to evaluate the effects of NCB-02 on endothe-
lial function and its biomarkers in patients with
type 2 diabetes. The beneficial effects of NCB-02 on
endothelial function may be attributed to its potent
antioxidant, anti-inflammatory properties and its
ability to decrease levels of these inflammatory
mediators and malondialdehyde, a marker of oxida-
tive stress.
Conclusion
Type 2 diabetes is associated with endothelial
dysfunction, which is in turn associated with in-
creases in oxidant and inflammatory biomarkers
such as malondialdehyde, IL-6, TNFα and ET-1.
Treatment with NCB-02 and atorvastatin signifi-
cantly improved endothelial function in conjunction
© 2008 Adis Data Information BV. All rights reserved.
249
with reductions in the levels of inflammatory cyto-
kines and markers of oxidative stress. However, the
present study was a proof of concept study per-
formed on a limited number of participants; larger,
randomized clinical trials are needed to investigate
the effects of different doses of NCB-02 and in
combination with lipid-lowering agents on endothe-
lial dysfunction and to confirm the beneficial role of
NCB-02 in patients with increased cardiovascular
risks.
Acknowledgements
The authors would like to thank Dr S.K. Mithra, Execu-
tive 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.
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Correspondence: Dr P. Usharani, Department of Clinical
Pharmacology and Therapeutics, Nizam’s Institute of
Medical Sciences, Panjagutta, Hyderabad-500 082, Andhra
Pradesh, India.
E-mail: ushapingali@yahoo.com
Drugs R D 2008; 9 (4)