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344 Bamosa et al Indian J Physiol Pharmacol 2010; 54(4)
Indian J Physiol Pharmacol 2010; 54 (4) : 344–354
EFFECT OF NIGELLA SATIVA SEEDS ON THE GLYCEMIC CONTROL
OF PATIENTS WITH TYPE 2 DIABETES MELLITUS
ABDULLAH O. BAMOSAa,*, HUDA KAATABIa, FATMA M. LEBDAa,
ABDUL-MUHSSEN AL ELQb AND ALI AL-SULTANb
aDepartment of Physiology,
College of Medicine,
King Faisal University, Dammam, Saudi Arabia
and
bDepartment of Internal Medicine,
College of Medicine, King Faisal University,
Dammam, Saudi Arabia
( Received on October 5, 2009 )
Abstract : Diabetes mellitus is a common chronic disease affecting millions
of people world wide. Standard treatment is failing to achieve required
correction of blood glucose in many patients. Therefore, there is a need for
investigating potential hypoglycemic drugs or herbs to improve glycemic
control in diabetic patients.
Nigella sativa seeds were used as an adjuvant therapy in patients with
diabetes mellitus type 2 added to their anti-diabetic medications. A total of
94 patient were recruited and divided randomly into three dose groups.
Capsules containing Nigella sativa were administered orally in a dose of
1, 2 and 3 gm/day for three months. The effect of Nigella sativa on the
glycemic control was assessed through measurement of fasting blood glucose
(FBG), blood glucose level 2 hours postprandially (2 hPG), and glycosylated
hemoglobin (HbA1c). Serum C-peptide and changes in body weight were
also measured. Insulin resistance and β-cell function were calculated using
the homeostatic model assessment (HOMA2).
Nigella sativa at a dose of 2 gm/day caused significant reductions in
FBG, 2hPG, and HbA1c without significant change in body weight. Fasting
blood glucose was reduced by an average of 45, 62 and 56 mg/dl at 4, 8 and
12 weeks respectively. HbA1c was reduced by 1.52% at the end of the 12
weeks of treatment (P<0.0001). Insulin resistance calculated by HOMA2
was reduced significantly (P<0.01), while β-cell function was increased
(P<0.02) at 12 weeks of treatment.
The use of Nigella sativa in a dose of 1 gm/day also showed trends in
improvement in all the measured parameters but it was not statistically
significant from the baseline. However, no further increment in the
*Corresponding Author : Abdulla O. Bamosa; Department of Physiology, College of Medicine, King Faisal
University, P.O. Box 2114, Dammam 31451, Saudi Arabia; Tel.: 00966505853161
Fax : 0096638575329; E-mail address: aosbamosa@gmail.com
Indian J Physiol Pharmacol 2010; 54(4) Effect of Nigella Sativa Seeds on the Glycemic Control 345
emphasized the beneficial effects of Nigella
sativa in diabetic animals (8–11). These
studies clearly showed that Nigella sativa
significantly reduced the elevated blood
glucose levels of different animals with
experimentally-induced diabetes mellitus (8,
9). The evident antidiabetic effect of Nigella
sativa was attributed to its insulinotropic
action (10, 11), and the antioxidant properties
which decrease the oxidative stress
and preserve pancreatic β-cell integrity
(12–14). The glycemic control obtained by
Nigella sativa was also attributed to its
extrapancreatic actions, mainly the inhibition
of hepatic gluconeogenesis (15, 16).
In addition, previous studies did not
reveal any harmful effect of Nigella sativa
on renal and hepatic functions. On the
contrary, the reported pharmacological
actions of Nigella sativa oil include
protection against nephrotoxicity and
hepatotoxicity induced by either diseases,
drugs or chemical compounds (17–21). The
antioxidant and anti-inflammatory activities
of Nigella sativa are considered the main
factors responsible for its nephroprotective
and hepatoprotective effects (22).
The effects of Nigella sativa on diabetic
patients are not adequately investigated.
beneficial response was observed with the 3 gm/day dose. The three doses
of Nigella sativa used in the study did not adversely affect either renal
functions or hepatic functions of the diabetic patients throughout the study
period.
In Conclusion : the results of this study indicate that a dose of 2 gm/
day of Nigella sativa might be a beneficial adjuvant to oral hypoglycemic
agents in type 2 diabetic patients.
Key words : Nigella sativa diabetes mellitus type 2
fasting blood glucose glycosylated hemoglobin
C-peptide insulin resistance
INTRODUCTION
Diabetes mellitus is one of the most
common chronic diseases affecting millions
of people worldwide with a large negative
impact on the patient’s health. Type 2
diabetes is characterized by Hyperglycemia
that arises from insulin resistance and/or
impaired beta cell function/insulin secretion
(1). Umpierrez GE, et al. (2) demonstrated
that hyperglycemia was associated with
increased morbidity and mortality. In
addition, newest published data has
raised the concern about the benefit of
treatment of hyperglycemia to achieve near-
normoglycemia in intensive care patients (3).
Nigella sativa Linn is an annual
plant belongs to the botanical family of
Ranunculaceae (4) and commonly grows in
Europe, Middle East and Western Asia.
Nigella sativa known as black cumin is
usually used as a traditional medicine in
Arabian countries (5), Indian sub-continent
(6) and Europe (7), for a wide range of
illnesses including brochial asthma,
headache, dysentery, infections, back pain,
hypertension and gastrointestinal problems
(22).
Several previous studies strongly
346 Bamosa et al Indian J Physiol Pharmacol 2010; 54(4)
Well controlled clinical studies demonstrating
the antidiabetic effect of Nigella sativa in
human subjects are still lacking. Only few
surveys showed that some diabetic patients
utilize Nigella sativa to improve glycemic
control (23, 24). Therefore the aim of this
study was to investigate the effect of three
doses of Nigella sativa on glycemic control
in type 2 diabetic patients.
MATERIALS AND METHODS
Patient selection
The study was conducted on 94 patients
(43 males and 51 females) with uncontrolled
diabetes mellitus type 2. The patients in the
study were enrolled from King Fahad
University Hospital and Al-Agharabia
Primary Health Care Center, Al-Khobar,
Saudi Arabia. Diabetes was diagnosed
according to the criteria of the American
Diabetes Association (25).
The selection of uncontrolled diabetes was
made on the basis of two successive readings
of HbA1c more than 7%, done three months
apart. Patients included were of age 18–60
years, treated only with oral hypoglycemic
drugs (glipenclamide, metformin, rosiglitazone),
ready for regular follow up and had HbA1c
> 7%. Patients were excluded if they had
chronic cardiac illness (ischeamic heart
disease, heart failure, cardiac arrythmias),
chronic liver disease (hepatic failure, active
hepatitis, liver cirrhosis), renal complications
and any other chronic deplitating illness.
Patients were also excluded if they had
compliance less than 90% and if their
standard medications were changed during
the 12 weeks of the study. All patients were
fully informed about the purpose and
duration of the study and they were free
to leave the study at any time. Written
informed consent was obtained from all
participants. The study has been approved
by the research ethics committee of King
Faisal University – Dammam, reference
number KFU-LEC-132.
Study design
Nigella Sativa seeds (Bioextract (Pvt) Ltd,
Sri Lanka) were provided in form of capsules.
Each capsule contained 500 mg of grounded
Nigella Sativa. Recruited type 2 diabetic
patients fulfilling above criteria were
randomly divided into 3 groups (cohort of 10
patients in sequence for each group) and
were administered 3 different oral doses of
Nigella sativa (1 gm, 2 gm, and 3 gm per
day for 12 weeks). These doses were selected
on the basis of a previous study conducted
on healthy human volunteers, where a daily
ingestion of 2 gm Nigella sativa was effective
in reducing blood glucose following one week
of administration (26). Therefore, in this
study we went up and down by 1g around
the previous effective dose (2 g) in the above
quoted study.
All patients in the three groups were
subjected to history taken, physical
examination, laboratory investigations and
self monitoring of blood glucose (SMBG). In
addition body mass Index (BMI) was
calculated for each patient before initiation
of treatment and 12 weeks after.
Every patient was requested to do SMBG
of both FBG and 2hPG before initiation of
therapy and after one and four days of
treatment initiation, then weekly for 12
weeks. SMBG readings have a reliability of
Indian J Physiol Pharmacol 2010; 54(4) Effect of Nigella Sativa Seeds on the Glycemic Control 347
Evaluation of insulin resistance (IR)
and β-cell function was obtained using the
updated homeostatic model assessment
(HOMA2) which is developed from original
HOMA1 described by Matthews and
coworkers (27). The output of the
computerized HOMA2 model is calibrated to
give normal β-cell function of 100% and
normal IR of 1 (28).
Statistical analysis
Statistical analysis was performed using
the Statistical Package of Social Science
(SPSS) version 11. Data are presented as
means±standard error of the means (SEM).
All experimental results are compared to
their own baseline values by paired Student’s
t-test. The level of significance was set at
P<0.05. The corresponding parameters in the
three groups were also compared using
analysis of variance (ANOVA). “F” test
was performed to determine statistical
significance of all groups. In case of
significant “F” test (P<0.05), further analysis
was made by LSD (least significant
difference) multiple range-test to find inter-
groupal significance. A probability of P<0.05
was considered significant.
RESULTS
Baseline data including the number of
patients, age, sex, duration of diabetes, dose
of Nigella sativa and duration of treatment
in each group are outlined in Table I. There
was no significant difference between the
three groups, compared by ANOVA, except
for age between groups 3 and 2. The number
of patients excluded was higher at the 3 gm
group because of non compliance to
medication. Most of excluded patients in this
10 mg/dl. Investigations including liver and
renal function tests, FBG, 2hPG, fasting C-
peptide, and HbA1c were done for all patient
as baseline and at 4, 8 and 12 weeks after
initiation of therapy.
During the first 2 weeks of administration
of Nigella sativa, patients were contacted
daily by telephone, and were enquired about
any new symptoms and compliance to
medications. They were also asked to report
any change in their medication or lifestyle
throughout the study.
Analytical methods
Serum glucose was measured by Glucose
Flex reagent cartridge, supplied by Dade
Behring. The automated assay analyzer
was Dimension clinical chemistry system,
Germany. HbA1c was measured by Gold
Reagent Kit-HbA1c by Drew Scientific Ltd,
using Hb Gold Analyzer. C-peptide was
measured by Immulite C-peptide kit by
EURO/DPC Ltd using Immulite Analyzer.
The glucometer brand used for SMBG was
Accu-Chek Go, Roche Diagnostic GmbH,
Germany.
Blood samples were collected after at
least 8 hours of fasting and 2 hours after
breakfast. Blood was collected into plain
tubes (without anticoagulant) and allowed to
clot. Then it was centrifuged at 3000 rpm
for 8 minutes to separate the serum. Serum
was stored and kept frozen at – 20oC for up
to 1 week to be used for determination of
glucose, C- peptides, liver and renal function
tests. Another portion of blood was collected
into EDTA – coated tubes. The hemolysates
were prepared after sample collection and
stored at 4oC to be used within 2 days for
estimation of HbA1c.
348 Bamosa et al Indian J Physiol Pharmacol 2010; 54(4)
TABLE I : No of patients, age, duration of diabetes,
dose of Nigella sativa, and duration of
supplementation in 3 groups of Patients
with type 2 diabetes mellitus.
Group I Group II Group III
No. of 30 32 32
patients (16 females) (18 Females) (17 females)
No. of 7 6 13
patients
excluded
Age (years) 47.80±1.42 49.63±0.97 44.91±1.88
Mean±SEM
Duration of 7.9±1.02 7.12±0.92 6.74±1.08
diabetes (years)
Mean±ESM
Dose of 500 mg 1 gm 1 gm
Nigella twice daily twice daily thrice daily
sativa (1 gm/day) (2 gm/day) (3 gm/day)
Duration of 12 weeks 12 weeks 12 weeks
Nigella sativa
supplementation
Age and duration of diabetes were non
significantly different between the three groups,
except for age that was significantly lower in
group 3 compared to group 2, using ANOVA.
group changed, on their own, to 2 gm dose
in the last 4 weeks of treatment.
Generally, the three doses of Nigella
sativa were well tolerated with only three
patients who experienced a mild epigastric
discomfort that settled down after taking the
capsules post meals.
One gram of Nigella sativa
supplementation for 12 weeks to type 2
diabetic patients (group 1), induced a
moderate decline in the levels of FBG and
2hPG, starting after 4 weeks of treatment
and continued thereafter. However, this
decline was statistically not significant when
compared to corresponding baseline levels
(Table II). On the other hand, SMBG showed
a significant reduction in FBG after 8 weeks
and in 2hPG after 8 and 12 weeks of
treatment (Table III). Other parameters were
not significantly changed by this dose (Table
II).
Patients in group 2, treated with 2 gm/
day Nigella sativa, had a significant reduction
in FBG level throughout the 12 weeks
treatment period. FBG was reduced by an
average of 45, 62, and 56 mg/dl at 4, 8, and
12 weeks, respectively (Table II). The 2hPG
level, also, showed significant drop after 4
and 8 weeks of treatment. Further, SMBG
showed a significant drop in FBG and 2hPG,
starting one day after treatment initiation
and continued throughout most of the
treatment points (Table III). This dose of
Nigella sativa was, also, able to significantly
lower HbA1c by 1.52% after 12 weeks of
treatment (7.57%±0.3% vs. 9.09%±0.24%,
P<0.0001) (Table II). Group 3 patients, who
received 3 gm/day of Nigella sativa for 12
weeks, showed statistically significant
reduction in FBG levels after 4, 8, and 12
weeks (Table II). Similarly, SMBG displayed
a significant fall in FBG in most time points
(Table III). Also, this dose produced a
considerable reduction in HbA1c by 2%
(7.31%±0.37% vs. 9.35%±0.41%, P<0.0001)
(Table III). On the other hand, C-peptide did
not change significantly by the 2 and 3 gm
doses.
Insulin resistance, calculated by HOMA2
was significantly reduced by 2 gm daily
supplementation of Nigella sativa (2.37±0.20
vs. 3.20±0.36, P<0.01, n = 23). Furthermore,
this dose of Nigella sativa produced a
significant elevation in β-cell function,
calculated with HOMA2 (63.63%±9.59% vs.
45.03%±6.28%, P<0.02, n = 23) at the end of
the 12 weeks treatment period (Table II).
However, other doses used (1 and 3 gm) did
not produce any significant change in both
Indian J Physiol Pharmacol 2010; 54(4) Effect of Nigella Sativa Seeds on the Glycemic Control 349
TABLE II : Mean±SEM of fasting blood glucose (FBG), 2 hours post prandial blood glucose (2hPG),
hemoglobin A1c (HbA1c) fasting C-peptide, insulin resistance index, beta cell function and body
mass index (BMI), in type 2 diabetic patients, treated with Nigella sativa – 1 g/day (group1) –
2 g/day (group 2) – 3 g/day (group 3), for 12 weeks, compared to the corresponding baseline values.
Group 1 Group 2 Group 3
Parameter Baseline Treatment duration Baseline Treatment duration Baseline Treatment duration
Values in weeks Values in weeks Values in weeks
4 8 12 4 8 12 4 8 12
FBG
(mg/dL)
Mean 189 186 171 171 219 174 157 162 204 176 157 169
±SEM ±14.3 ±13.8 ±10.1 ±7.8 ±12.3 ±10.1 ±10.8 ±9.2 ±18.2 ±15.2 ±9.9 ±16.4
n 222220212626192416161416
p NS NS NS <0.0001 <0.001 <0.001 0.01 0.006 0.04
2hPG
(mg/dL)
Mean 286 244 241 218 289 213 231 256 277 301 229 234
±SEM ±23.3 ±22.5 ±19.2 15.6 ±24.2 ±27.8 ±26.5 ±28.1 ±54.3 ±54.3 ±9.9 ±80.3
n 997 512127106 6 44
p NS NS NS <0.04 <0.04 N S NS NS NS
HbA1c (%)
Mean 8.36 8.01 9.09 7.57 9.35 7.31
±SEM ±0.31 — — ±0.27 ±0.24 — — ± 0.30 ±0.41 — — ±0.37
n21 2124 2417 17
p NS <0.0001 <0.0001
C-peptide
(ng/mL)
Mean 2.96 3.16 3.02 2.66 3.54 3.44
±SEM ±0.33 — — ±0.32 ±0.32 — — ±0.26 ±0.36 — — ±0.47
n17 1724 2413 13
p NSNSNS
Insulin
resistance
index
Mean 2.75 2.82 3.20 2.37 4.11 2.98
±SEM ±0.34 — — ±0.26 ±0.36 — — ±0.20 ±0.55 — — ±0.49
n17 1723 239 9
p N S ‹0.01 N S
Beta cell
function %
Mean 61.75 59.12 45.03 63.63 41.89 88.90
±SEM ±7.79 — — ±8.19 ±6.28 — — ±9.59 ±9.83 — — ±36.05
n17 1723 239 9
P N S ‹0.02 N S
BMI (kg/m2)
Mean 33.6 33.3 28.9 29.4 31.63 31.61
±SEM ±1.53 — — ±1.53 ±0.95 — — ±0.94 ±1.47 — — ±1.50
n22 2224 2416 16
P NSNSNS
n: number of patients. NS: not significant.
P: significance of difference from baseline values, using Student’s t-test, for paired data.
Insulin resistance and beta cell function% were calculated using HOMA2 calculator.
350 Bamosa et al Indian J Physiol Pharmacol 2010; 54(4)
Fig. 1 : Changes in fasting blood glucose (FBG), post prandial blood glucose (PPBG), glycosylated hemoglobin
(HbA1c), fasting C-peptide, in type 2 diabetic patients, received 1 g/day (group 1), 2 g/day (group 2),
and 3 g/day (group 3) of Nigella sativa, for 12 weeks. The corresponding parameters in the three
groups were compared using ANOVA.
Data are Mean±SEM of the values as percentages of the corresponding baseline values, considering
baseline values equal 100.
: significance of difference between groups 2 and 1. (P<0.05)
Δ: significance of difference between groups 3 and 1. (P<0.05)
o : significance of difference between groups 2 and 3. (P<0.05)
IR and β-cell function calculated with
HOMA2 (Table II).
Inter groups comparison, using ANOVA,
showed significant reduction in FBG level in
group 2 compared to group 1 after 4, 8, and
12 weeks of treatment. However, FBG was
not significantly different in group 3 when
compared to group 1. 2hPG levels in group
2 were reduced when compared to group 1
and 3, yet the decrease was statistically
significant only after 4 weeks treatment,
compared to group 3 (Fig. 1). FBG recorded
through SMBG was significantly decreased
in groups 2 and 3 compared to group 1
in most reading points. However, the
glucometer readings for 2hPG in group 2
were significantly decreased after 1 day and
8 weeks when compared to group 1 and only
after 4 days of treatment when compared to
Indian J Physiol Pharmacol 2010; 54(4) Effect of Nigella Sativa Seeds on the Glycemic Control 351
TABLE III : Mean (+SEM) of fasting blood glucose (FBG), 2 hours post prandial blood glucose (2hPG), in type
2 diabetic patients, received 1g/day (group 1), 2 g/day (group 2), and 3g/day (group 3) of Nigella
sativa, for 12 weeks, measured by self monitoring Glucometer (SMBG). The corresponding parameters
were compared to their corresponding baseline values using student’s t-test for paired data.
FBG (mg/dL) ) by SMBG
Treatment duration in weeks
Baseline (0) 1a 1b 4 8 12
Group 1n 193 (8)25 179 (10)25 181 (11)25 178 (11)20 165 (10)*16 195 (19)19
Group 2n 230 (13)25 181 (13)Δ25 177 (14)Δ25 210 (12)25 160 (9)Δ22 157 (10)Δ22
Group 3n 221 (16)21 173 (13)Δ21 172 (14)Δ20 195 (12)21 158 (12)Δ19 149 (15)Ë%13
2hPG (mg/dl) by SMBG
Group 1n 288 (13)23 270 (16)23 256 (17)23 262 (16)19 231 (16)o15 248 (16)*18
Group 2n 302 (12)23 243 (13)Δ23 254 (13)Δ23 274 (5)*23 219 (12)Δ18 242 (13)o14
Group 3n 294 (17)18 247 (19)*18 272 (16)18 274 (19)19 223 (20)*16 238 (26)11
1a is the reading one day after treatment, 1b is the reading 4 days after treatment.
4, 8 and 12 represent the average readings of (1-4), (5-8) and (9-12) weeks respectively.
* : significantly different from baseline value. (P<0.05)
o : significantly different from baseline value. (P<0.01)
Δ: significantly different from baseline value. (P<0.001)
n: number of patients.
Fig. 2 : Changes in the fasting blood glucose (FBG), and post prandial blood glucose (PPBG) readings using self
monitoring glucometer, in type 2 diabetic patients, received 1 g/d (group 1), 2 g/d (group 2), and 3 g/d
(group 3) of Nigella sativa, for 12 weeks, the readings in the three groups were compared using ANOVA.
Data are Mean±SEM of the values as percentages of the corresponding baseline values, considering
baseline values equal 100.
1a: is the reading taken one day after treatment. 1b: is the reading taken 4 days after treatment.
4, 8 and 12 represent the average readings of (1-4), (5-8) and (9-12) weeks respectively.
: significance of difference between groups 2 and 1. (P<0.05)
Δ: significance of difference between groups 3 and 1. (P<0.05)
o : significance of difference between groups 2 and 3. (P<0.05)
352 Bamosa et al Indian J Physiol Pharmacol 2010; 54(4)
in blood glucose that was supported
by a corresponding reduction in HbA1c.
Glycosylated hemoglobin reflects an
integrated index of diabetic control for 6–8
weeks period before the measurement (29).
These data are in agreement with a
number of studies carried out in animal
models of diabetes mellitus. Nigella sativa
has been reported to induce reduction in
plasma glucose levels in alloxan-induced
diabetic rabbits (8), as well as in
streptozotocin induced diabetic rats (11, 16,
20), and found to be very effective in
restoring glucose homeostasis in sand rat
models (9).
On the other hand, the hypoglycemic
effect of Nigella sativa was not demonstrated
in certain studies using, normal rats (30),
and streptozotocin-induced diabetic rats (31).
This disparity might be due to differences
in animal species, and/or doses and types of
Nigella sativa extract used.
The hypoglycemic effect of Nigella sativa
found in this study is most probably due to
dual effect of this plant on insulin resistance
and β-cell function as evident from HOMA2
calculations. The 2 gram dose managed to
reduce insulin resistance (P<0.03) and at the
same time seems to increase β-cell function
(P<0.02). This finding is supported by the
study of Le et al (30), who reported that
treatment with Nigella sativa extract induced
a decrease in fasting plasma levels of insulin
and sensitized rat hepatocytes to the action
of insulin by enhancing the activity of two
major intracellular signal transduction
pathways of insulin receptor. Conceivably,
insulin resistance could be decreased at
target tissues by the same mechanisms. The
group 3 (Fig. 2). HbA1c was significantly
reduced in groups 2 and 3 compared to group
1, but, non-significantly different in group 2
compared to group 3. On the other hand,
fasting C-peptide levels were not significantly
different among the three groups (Fig. 1).
DISCUSSION
The results of this study clearly show a
hypoglycemic effect of Nigella sativa in type
2 diabetic patients. The optimum dose seems
to be 2 gm/day of Nigella sativa powder. The
effect of Nigella sativa on fasting and
postprandial blood glucose levels took place
within one day of treatment. HbA1c was
lowered significantly by both 2 & 3 grams
daily supplementation of Nigella sativa, but
was not affected significantly by the one
gram dose. The results, also, indicate that
Nigella sativa is well tolerated in the dose
range used. The epigastric pain experienced
by 3 patients could have been due to acidity,
as it disappeared when the patients took the
capsules after meals.
Interestingly, the doses used in this study
covered the anticipated effect of the drug on
the parameters studied. While one gram
Nigella sativa was unable to produce
significant hypoglycemic effect, the 2 gram
was enough to do so. However, the 3 gram
dose failed to produce significant further
glucose lowering effect. This could be partly
due to less compliance of patients in the
higher dose group which made its “n” values,
in many parameters, smaller. Another
possible cause, of less effect for the 3gm dose,
is the presence of other ingredients in the
Nigella sativa seeds that produce a counter
acting effect at this higher dose. The 2
gram dose produced a sustained reduction
Indian J Physiol Pharmacol 2010; 54(4) Effect of Nigella Sativa Seeds on the Glycemic Control 353
mechanism of improved tissue sensitivity
to insulin action by Nigella sativa may
be related to reduction in oxidative stress
(32–34). Several studies have documented
the antioxidant properties of Nigella sativa
(22, 35).
In conclusion, the present study propose
that Nigella sativa in a dose of 2 gm/day
supplemented to Type 2 diabetes mellitus
patients improves significantly the laboratory
parameters of glycemia and diabetes control.
However, further randomized placebo
controlled clinical trials are needed to prove
the promising findings reported in this study.
ACKNOWLEDGMENTS
This study was supported by king
Abdulaziz City for Science and Technology.
Thanks are due to Professor Shahid Baig
from department of clinical neuroscience,
and Dr. Amro Ahmad Fouad from
pharmacology division at the biomedical
department in the college of medicine in Al-
Ahsa for reviewing the manuscript. Authors
are thankful for Mr. Naseem & Mr. Khaisar
for technical assist.
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