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The ethanolic extract of seeds of Cuminum cyminum (C.c) was found to improve glucose tolerance to the tune of around 18.3% (P \ 0.01) in normal rats and shows around 17.7% (P \ 0.01) and 17.1% fall on blood glucose levels at 0–300 and 0–1440 min, respectively, on streptozotocin-induced diabetic rats at an oral dose of 250 mg/Kg body weight. The extract has also been found to improve around 26.7% (P \ 0.01) glucose intolerance on 14th day post treatment in high fructose fed streptozotocin-induced diabetic rats. The extract was also found to have antidyslipidemic activity as evident by 21.04% (P \ 0.01) decline in serum triglycerides, 22.7% (P \ 0.01) decline in total serum cholesterol, and 16.9% of decline in serum LDL-C, respectively, along with 12.2% (P \ 0.05) increase in serum HDL-C on high fat diet fed male Syrian golden hamster. The extract was also found inhibitory to eye lens aldose reductase (EC 1.1.1.21) with IC 50 value of 7.07 lg/ml as compared to the standard AR inhibiting compound Quercetin which showed IC 50 2.35 lg/ml. The extract was also found inhibitory to a-glucosidase with IC 50 value of 100 lg/ml as compared to known drug Acarbose which showed IC 50 of around 25 lg/ml.
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ORIGINAL RESEARCH
Antidiabetic and antidyslipidemic activities of Cuminum cyminum
L. in validated animal models
Rohit Srivsatava Swayam Prakash Srivastava Natasha Jaiswal
Akansha Mishra Rakesh Maurya Arvind Kumar Srivastava
Received: 15 March 2010 / Accepted: 15 October 2010
ÓSpringer Science+Business Media, LLC 2010
Abstract The ethanolic extract of seeds of Cuminum
cyminum (C.c) was found to improve glucose tolerance to
the tune of around 18.3% (P\0.01) in normal rats and
shows around 17.7% (P\0.01) and 17.1% fall on blood
glucose levels at 0–300 and 0–1440 min, respectively, on
streptozotocin-induced diabetic rats at an oral dose of
250 mg/Kg body weight. The extract has also been found to
improve around 26.7% (P\0.01) glucose intolerance on
14th day post treatment in high fructose fed streptozotocin-
induced diabetic rats. The extract was also found to have
antidyslipidemic activity as evident by 21.04% (P\0.01)
decline in serum triglycerides, 22.7% (P\0.01) decline in
total serum cholesterol, and 16.9% of decline in serum
LDL-C, respectively, along with 12.2% (P\0.05) increase
in serum HDL-C on high fat diet fed male Syrian golden
hamster. The extract was also found inhibitory to eye lens
aldose reductase (EC 1.1.1.21) with IC
50
value of 7.07
lg/ml as compared to the standard AR inhibiting compound
Quercetin which showed IC
50
2.35 lg/ml. The extract was
also found inhibitory to a-glucosidase with IC
50
value of
100 lg/ml as compared to known drug Acarbose which
showed IC
50
of around 25 lg/ml.
Keywords Cuminum cyminum Glucose tolerance
Streptozotocin (STZ) Aldose reductase a-Glucosidase
Low-dosed STZ treated-high fructose fed rats
n2-neonatal rats Dyslipidemia
Introduction
Diabetes mellitus (DM) is a disease of civilization and the
prevalence of this disease has risen worldwide in large
parts because of an increase in obesity and sedentary life-
styles. About 90% DM patients are of type II DM with
insulin resistance which plays an important role in the
development of the disease. The progression of type II DM
begins with an impairment of glucose tolerance which is
often associated with a state of insulin resistance. Both
insulin resistance and decreased insulin secretion delivers
the pathophysiology of T2DM (Ravinet et al., 2004). In
T2DM the increased circulating glucose concentration is
associated with abnormalities in carbohydrate, protein, and
lipid metabolism and a variety of microvascular, macro-
vascular, neurological, and infectious complications (Tri-
pathi and Srivastava, 2006).
a-Glucosidase (EC 3.2.1.20) catalyzes the final step in
the digestive process of carbohydrates. Its inhibitors can
retard the uptake of dietary carbohydrates, and therefore,
suppress postprandial hyperglycemia one of the most for-
midable challenge of type II diabetes mellitus (Watanabe
et al., 1997). a-Glucosidase inhibitors such as acarbose,
miglitol, and voglibose are known to reduce postprandial
hyperglycemia primarily by interfering with the carbohy-
drate digesting enzymes and delaying glucose absorption.
Now a days, numerous a-glucosidase inhibitors have been
isolated from plants, some of which are of clinical impor-
tance (Lee, 2005).
Aldose reductase (EC 1.1.1.21) catalyzes the reduction
of glucose to the corresponding sugar alcohol, sorbitol,
which is subsequently metabolized to fructose by sorbitol
dehydrogenase through a pathway termed as polyol path-
way. Under normal physiological conditions, this pathway
plays a minor role in the glucose metabolism of most
R. Srivsatava S. P. Srivastava (&)N. Jaiswal A. Mishra
R. Maurya A. K. Srivastava
Divisions of Biochemistry and Medicinal and Process
Chemistry, Central Drug Research Institute,
Lucknow 226001, India
e-mail: swayam.cdri@gmail.com
Med Chem Res
DOI 10.1007/s00044-010-9483-2
MEDICINAL
CHEMISTR
Y
RESEARCH
tissues. In hyperglycemia associated with diabetes, how-
ever, cells undergoing insulin-dependent uptake of glucose
produce significant quantities of sorbitol due to poor pen-
etration by sorbitol through the cellular membranes and its
metabolism by sorbitol dehydrogenase. The resulting
hyperosmotic stress to cells is postulated to be the primary
cause for the development of such diabetic complications
as retinopathy, cataract, neuropathy, and nephropathy
(de la Fuente and Sonia Manzanaro, 2003).
Plants constitute a rich source of bioactive chemicals
(Sung et al., 2004). As many of them are largely free from
adverse effects and have excellent pharmacological actions,
these could lead to the development of new classes of pos-
sibly safer antidiabetic agents and diabetic complications.
Additionally, some flavonoids and polyphenols as well as
sugar derivatives are found to be effective on the inhibitory
activities of a-glucosidase and aldose reductase (Lee and
Kim, 2001). Therefore, much effort has been focused on the
plants for potentially useful products as commercial a-glu-
cosidase inhibitors and aldose reductase inhibitors as lead
compounds. Cuminum cyminum L. belongs to the family
Apiaceae is consumed in fairly large quantities by Indians.
Cumin is widely used in Ayurvedic medicine for the treat-
ment of dyspepsia, diarrhoea and jaundice. It also has sto-
machic, diuretic, carminative, emmanogogic, antispasmodic,
antimicrobial, fungicide, and tyrosine inhibitor properties
(Joshi, 2000; Kubo and Kinst-Hori, 1998). It is reported that
cumin seeds have antidiabetic effect on streptozotocin-
induced diabetic rats (Roman-Ramos, 1995) and hypolipi-
demic activity in alloxan-induced diabetic rats (Dhandapani
et al., 2002). Cuminaldehyde derived from cumin seed pos-
sess aldose reductase and aglucosidase inhibitory activities
(Lee, 2005) and antioxidant properties (Sultana et al., 2010).
Cumin seeds contain up to 14.5% lipids. They are reported to
contain 14 flavonoid glycosides; 7 belong to apigenin, 5 to
luteolin, and 2 to chrysoeriol group. Major constituents of the
essential oil include cuminaldehyde (20–40% of the oil) and
p-cymene (Khare 2004). The present study confirms the
antidiabetic, antidyslipidemic, a-glucosidase, and aldose
reductase inhibitory properties in the ethanolic extract of
C. cyminum seeds.
Materials and methods
Plant material
The seeds were shade dried, pulverized by a mechanical
grinder and passed through 100 mesh sieve and stored in a
tightly closed container for further use and termed crude
powder. The crude powder was extracted five times with
95% ethanol (one extraction in one day) at room temper-
ature by percolation method. The combined extracts were
evaporated to dryness in vacuum to afford the ethanolic
extract.
Animals
Eight to ten weeks old male rats of Sprague-Dawley strain
weighing 160 ±20 g were obtained from animal colony of
Central Drug Research Institute, Lucknow. The rats were
housed in an air-conditioned room at 25 ±1°C with a
lighting schedule of 12 h light and 12 h dark. A standard
pellet diet and tap water were given ad libitum.All ethical
manners for use of animals in scientific researches have
been carefully considered.
Chemicals
Streptozotocin, Dulbeco minimum essential medium
(DMEM), Fetal bovine (calf) serum, Penicillin G, Strep-
tomycin, Gentamycin/Amphotericin B, HEPES, Trypan
blue, Phosphate buffer saline(PBS), Trypsin Solution,
Glucose free DMEM, Insulin, Tris, 2-deoxy-[3H] D-glu-
cose, Scintillation cocktail, Dexamethasone, Metformin,
a-Glucosidase, p-nitrophenyl-a-D-glucopyranoid (PNPG),
Glutathione, was purchased from Sigma-Aldrich, St. Louis,
USA. All other chemicals used were of analytical grade.
Induction of diabetes
The animals were fasted for 16 h prior to the induction of
diabetes. STZ freshly prepared in citrate buffer (0.1 M, pH
4.5), was immediately injected intraperitoneally (i.p.) to
rats dose of 60 mg/kg. Diabetes in rats was identified by
polydipsia, polyuria and by measuring fasting blood glu-
cose levels 48 h after injection of STZ. Rats with blood
glucose levels above 270 mg/dl were selected for
experiments.
Experimental regimen
Experimental design for glucose uptake in L6 myoblasts
Stock cultures of L6 myoblasts were maintained in
DMEM supplemented with 10% (v/v) FBS, streptomycin
(200 lg/ml), penicillin G (100 lg/ml), and Amphotericin
B (25 lg/ml) under an atmosphere of 5% CO
2
/95%
humidified air at 37°C. For differentiation into myotubes,
cells were reseeded in 24-well plate containing DMEM
media (10% FBS) for overnight culture. When cells were
nearly confluent, 10% FBS containing DMEM media
medium was replaced with 2% FBS containing DMEM
media for differentiation into myotubes. The cells were
maintained for another 5 to 7 days and media were chan-
ged every 48 h prior to use these in experiments.
Med Chem Res
Glucose uptake assay
Measurement of radio-labeled 2-deoxyglucose uptake was
carried outs essentially as described by Somwar (Somwar
et al.1998) with partial modifications. Differentiated L6
mature myotubes cultured on 24-well plates were treated
with the desired concentrations of the test extract or stan-
dard drug for 18 h. After that, cells were washed three
times with Krebs–Ringer N-(2-hydroxyethyl) piperazine-
N-2-ethanesulfonic acid (HEPES) buffer saline containing
140 mM NaC1, 5 mM KCl, 1 mM CaCl
2
, 2.5 mM MgSO
4
,
and 20 mM HEPES. For glucose uptake measurement,
cells were incubated in HEPES buffer saline (HBS) con-
taining 3 lCi radio-labeled 2-deoxy-[3H] D-glucose and
20 lM unlabeled 2-deoxyglucose for 15 min. The reaction
was terminated by three quick washes with ice-cold
HEPES buffer saline. Cells were collected in 0.1 N NaOH
and cell-associated radioactivity (count per minute) was
determined by liquid scintillation counter. The results were
expressed as % increase in glucose uptake as compared to
controls. Backgrounds CPM were subtracted from control
and experimental.
Experimental design for normoglycemic rats
The 16 h fasted rats were divided into 3 groups (n=6 per
group) as follows:
(a) Group I served as a control received 1.0% gum
acacia, (b) Group II received test sample at the dose of
250 mg/kg body weight orally, and (c) Group III received
the standard hypoglycaemic drug Metformin at a dose of
100 mg/kg body weight.
The rats of all groups were given sucrose (10 g/kg body
weight, orally) 30 min post administration of the test
sample. Blood samples were collected from the tail vein
just prior administration of test sample, i.e., 0 min and at
30, 60, 90, and 120 min after the sucrose load. Blood
glucose levels were measured immediately by glucostrips
(Roche). Food but not water was withheld from the cages
during the experimentation (Tiwari et al., 2008).
Experimental design for streptozotocin-induced diabetic
rats
Male rats of Sprague-Dawley strain (160 ±20 g) were
made diabetic by a single intraperitoneal injection of STZ
(60 mg/kg body weight dose in 0.1 M citrate buffer, pH
4.5). Two days later blood samples were drawn from tail
vein and glucose levels were determined by glucostrips
(Roche) to confirm the induction of diabetes. The diabetic
rats were divided into three groups (n=6 per group) as
follows: (a) Group I termed as control rats were given 1.0%
gum acacia orally, (b) Group II termed as experimental
group were given test sample at the dose of 250 mg/kg
b.w., and (c) Group III termed as standard drug treated
group were given Metformin at 100 mg/kg b.w. The blood
samples were collected from tail vein just prior to admin-
istration, i.e., 0 min and thereafter 30, 60, 90, 120, 180,
240, 300, and 1440 min after test sample administration.
Food but not water was withheld from the cages during the
experimentation. The % fall in blood glucose values from
0–300 to 0–1440 min by plant extracts were calculated
according to the area under curve (AUC) method. The
average fall in AUC in experimental group compared to
control group was always termed as % antihyperglycemic
activity.
Experimental design for high fructose high fat fed
streptozotocin-induced diabetic rats
Rats of Sprague-Dawley strain (160 ±20 g) were divided
into two groups equally, one group were put on normal
sucrose diet (NSD) regime, and second group were fed
with high fructose high fat diet (HFD 60% fructose, 13%
saturated fat, and vital minerals, vitamins). After 4 weeks
feeding, blood was withdrawn from the retro-orbital plexus
of eye for the estimation of the lipid profile. After the
feeding of the respective diet, the half of the rats in each
group was given 45 mg/kg dose STZ injection. The rats
with the fasting PGL of C280 mg dl
-1
were considered
diabetic and selected for further pharmacological studies.
The rats were divided into four groups as follows: (a)
Group 1 Rats feed with Normal Sucrose Diet, (b) Group II
Rats feed with High-fructose high-fat diet, (c) Group III
Rats with High-fructose high-fat diet ?STZ (diabetic
control, received vehicle), (d) Group IV Rats feed with
High-fructose high-fat diet ?STZ (treatment group test
sample 100 mg/kg b.w.), (e) Group IV Rats feed with
High-fructose high-fat diet ?STZ (treatment group refer-
ence drug 100 mg/kg b.w.)
Biochemical estimations Insulin, TG, total Cholesterol,
LDL-C, and HDL-C were carried out on 0 day and 7th–
14th days after the administration of test sample. The rats
were allowed to continue to feed on their respective diets
until the end of the study. Plasma insulin levels were
assayed using an enzyme–linked immunosorbant assay kit
(Mercodia, Uppsala, Sweden). The degree of insulin
resistance was estimated by using Homeostasis Model
Assessment (HOMA) as an index of insulin resistance
(Mlinar et al., 2007).
Experimental design for neonatal-streptozotocin-induced
diabetic rats
Two-day-old SD rats, (weighing 5–8 g), were given
80 mg/kg i.p. of STZ in citrate buffer 0.1 M, pH 4.5. Non
Med Chem Res
diabetic control group receives only buffer i.p. After
4 weeks of age, rats were separated from their mothers and
acclimatized with free access to food and water. After
12 weeks, diabetes was identified by polydipsia, polyuria,
and by performing OGTT. Rats showing glucose intoler-
ance (high AUC) were included in the study. The diabetic
rats were divided into four groups (n=6 per group (a)
Group I non-diabetic control receives vehicle (1% gum
acacia), (b) Group II diabetic control receives vehicle (1%
gum acacia), (c) Group III treated group receives test
sample, 100 mg/kg b.w., (d) Group IV receives standard
oral hypoglycemic drug, 100 mg/kg b.w. The average fall
in AUC in experimental group compared to control group
was always termed as % antihyperglycemic activity
(Andrade-Cetto et al., 2007).
Experimental design for high fructose high fat diet fed male
Syrian golden hamsters
Male Syrian Golden hamsters weighing around 120 ±10 g
are used in the present study. The animals are given the
home made high fat diet for 20 days and after that, the
hyperlipidemic hamsters are divided into groups. Each
contains 6 animals per groups are dosed for 14 days as
follows: (a) Group-1 Normal Control (Vehicle treatment
only: 1.0% gum acacia). (b) Group-II Experimental
(Treatment with test sample at 100 mg/kg b.w.)
On day 7th and 14th, blood of each rat is withdrawn
from retro-orbital plexus in EDTA tubes. Serum is sepa-
rated for immediate analysis of total cholesterol, TG, HDL-
cholesterol, LDL-cholesterol, on Cobas Integra 400 plus
autoanalyzer (Narender et al., 2006).
Oral glucose tolerance test
In each case the oral glucose tolerance test (OGTT) was
performed as follows. Animals were deprived of food for
16 h before and during the experiment but were allowed
free access to water. The vehicle 1% gum acacia was given
to the control group whereas reference drug Metformin
(100 mg/kg b.w.) and test sample (100 mg/kg b.w.) were
orally administered to the experimental groups: 30 min
later glucose (3gm/kg b.w.) was orally administered to
each rat. Blood samples were immediately withdrawn
(0 min) and 30, 60, 90, and 120 min after administration of
glucose. Blood glucose concentration was estimated with
glucostrip using glucometer (Accu-check, Roche Diag-
nostics, USA).
Quantitative glucose tolerance of each animal was cal-
culated by area under curve (AUC) method using Prism
Software 3.0. The data were statistically analyzed by one-
way ANOVA followed by Dunnett’s test if there are more
than two groups. Student’s t tests were applied for
statistical analysis if there are only two groups. All the data
from the experiments are presented as mean ±S.E.M. The
results were considered statistically significant if the
p-values were less than 0.05 compared to baseline values.
Experimental design for a-glucosidase activity
This was done according to a slight modification of the
procedure reported by Cogoli et al. 100 ll of the purified
a-glucosidase (0.1 mg/ml) were added to the assay system
containing 100 ll of 67 mM phosphate buffer (pH 6.8) and
25 ll of glutathione (1.0 mg ml) and the volume was made
1 ml by using 775 ll of TDW. The reaction mixture was
incubated at room temperature for 10 min with the 10 ll
test sample (100 lM) dissolved 100% DMSO. Reaction
was started by the addition of 50 llp-nitrophenyl-a-D-
glucopyranoid (1 M) and increase in absorbance was
recorded at 405 nm for a period of 3 min at the interval of
30 s (Lebovitz 1997).
Experimental design for aldose reductase activity
Eye lenses of normal and diabetic rats of Sprague-Dawley
strains (weighing 160 ±20 g) were used as AR enzyme
source. According to the modified method of Hayman and
Kinoshita (1965), rat eye lens homogenate was prepared.
After cervical dislocation, immediately the lenses were
enucleated through posterior approach, washed with saline
and their fresh weight were recorded. Rat’s eye lenses were
pooled and a 10% lens homogenate was prepared in 0.1 M
phosphate buffer saline (pH 7.4). After centrifuge at
5,0009gfor 15 min in refrigerated centrifuge (4°C), the
supernatant was collected and kept in ice for the determi-
nation of AR activity and protein content.
Lens AR activity was measured according to the method
of Hayman and Kinoshita (1965). Aldose reductase activity
was spectrophotometrically assayed on a UV-10 Thermo
scientific double beam spectrophotometer by following the
decrease in the absorption of NADPH at 340 nm over a
3-min period with DL ±Glyceraldehyde as substrate. A
quartz cuvette containing 0.7 ml of sodium phosphate
buffer (67 mM, pH 6.2), 0.1 ml of lens supernatant
(25 910
-5
M), 0.1 ml of lens homogenate, 0.1 ml of
DL ±Glyceraldehyde (1 910
-3
M) (substrate) to a final
volume of 1 ml was read against a reference cuvette con-
taining all components but the substrate, DL ±Glyceral-
dehyde. The enzymatic reaction was started by the addition
of the substrate and the absorbance (O.D.) was recorded in
a double beam spectrophotometer at 340 nm for at least
3 min at 30 s interval. AR activity was expressed as DOD/
min/mg protein.
Protein content in the supernatant of the lens homoge-
nate was determined by the method of Lowry et al. (1951).
Med Chem Res
Results
Effect on glucose uptake by L6 myotubes
Figure 1represents the effect of C.c and metformin on
glucose uptake by L-6 myotubes. It is evident from the
result that C.c caused dose-dependent increase in glucose
uptake, i.e., at 0.1 lg/ml, increase was 9.07% followed by
19.8 and 36.4% at 1.0 and 10.0 lg/ml concentrations,
respectively. Metformin showed 26.8% increase in glucose
uptake at 500 lM concentration.
Effect on oral sucrose tolerance in normal rats
Figure 2a, b shows the effect of C.c and metformin on oral
sucrose tolerance in normal rats post sucrose load. C.c
showed significant (18.3%, P\0.01) improvement on oral
glucose tolerance post sucrose load in normoglycemic
rats at 250 mg/kg which is lower than that of metformin
which showed around 26% improvement (P\0.01) at
100 mg/kg.
Effect on blood glucose levels of streptozotocin-
induced diabetic rats
Single dose effect
Figure 3a, b shows the effect of C.C and metformin on
blood glucose profile of streptozotocin-induced diabetic
rats. It is evident from the figures that both C.c and met-
formin caused lowering in blood glucose profiles of
streptozotocin-induced diabetic rats. C.c showed around
17.7 and 17.1% decline in blood glucose levels during
0–300 and 0–1440 min post treatment, respectively. Met-
formin caused almost similar effect at a dose of 100 mg/kg
body weight caused, i.e., around 18.5 and 27.1% decline in
blood glucose levels during 0–300 and 0–1440 min,
respectively.
Multiple dose effect
Table 1presents the blood glucose, OGTT, serum insulin,
urea, uric acid and creatinine profiles in sham control, STZ-
induced diabetic rats and STZ-induced diabetic rats treated
with C.c, and metformin, respectively. Figure 4a, b pre-
sents the OGTT profiles in said groups. In STZ-induced
diabetic rats, oral administration of the C.c (100 mg/kg
b.w.) and metformin (100 mg/kg b.w.) for 14 days caused
significantly decline in blood glucose levels when com-
pared with the vehicle treated control group (Table 1). C.c
showed an improvement on OGTT, i.e., 14.4% (P\0.05)
on day 7 and 26.7% (P\0.01) on day 14 whereas met-
formin showed improvement on OGTT, i.e., 26.7%
(P\0.01) on day 7 and 31.1% (P\0.001) on day 14th
day, respectively, as compared to that in the control group
Fig. 4a, b. The plasma insulin concentration also increased
in C.c and metformin treated groups when compared to
control and metformin treated group. Serum urea, uric acid,
and creatinine levels were found significantly elevated in
Fig. 1 Effect of C.c on 2-deoxy glucose uptake by C.c on L6
myotubes
Fig. 2 a,bEffect of C.c and
metformin on oral sucrose
tolerance in normoglycemic rats
Med Chem Res
STZ-diabetic rats when compared to sham treated normal
rats. Oral administration of C.c for 14 days to STZ-induced
diabetic rats significantly (P\0.05) declined their urea,
uric acid, and creatinine levels.
Effect on oral glucose tolerance and serum lipid profiles
of high-fructose high-fat fed and low dosed
streptozotocin-induced diabetic rats
High fructose and high fat diet fed and low dosed strep-
tozotocin-induced diabetic rats showed abnormal glucose
tolerance on day 7 (Fig. 5a) and on day 14 (Fig. 5b) and
elevated serum cholesterol, triglycerides and LDL-C levels
and lowered HDL-cholesterol level compared to normal
diet fed rats (Table 2). Treatment of high fructose and high
fat diet rats with C.c and metformin significantly improved
their oral glucose tolerance as C.c treated groups showed
16.9% (P\0.05) and 20.9% (P\0.01) improvement on
OGTT of high fructose high fat diet fed rats on 7th and
14th day post treatment where as metformin showed 20.9%
(P\0.01) and 38.6% (P\0.001) improvement on OGTT
profile of these rats on day 7th and 14th day, respectively.
Treatment with C.c also declined their serum triglycerides
and cholesterol levels by 21.4% (P\0.01) and 19.7%
(P\0.05), respectively, after 14 days of treatment, how-
ever, there was found no significant effect of C.c on their
serum LDL-C and HDL-C levels. C.c extract caused
improvement of insulin resistance, as shown by the reduced
insulin level and lowered HOMA.
Effect on OGTT and serum insulin profiles
of neonatally streptozotocin-induced diabetic rats
Neonatally STZ-induced diabetic rats showed abnormal
glucose tolerance after 8 weeks compared to sham treated
control (Table 3). Treatment of C.c (100 mg/kg) or met-
formin (100 mg/kg) to these diabetic rats caused significant
improvement on their glucose intolerance. C.c treatment
improved their OGTT around 10.4% (P\0.05) and 27.7%
(P\0.01) on 7th and 14th days, respectively, Metformin
improved OGTT around 23.2 and 34.1% on 7th and 14th
days, respectively (Fig. 6a, b).
Fig. 3 a,bEffect on C.c and
metformin on blood glucose
levels of STZ-induced diabetic
rats
Table 1 Effect on antidiabetic profile after once daily repeated oral administration of C.c for 14 days in STZ-induced diabetic rats
Group Days OGTT AUC ±SEM Insulin (lg/l) Urea (mg/dl) Urk arid (mg/dl) Creatinine (mg/dl)
Normal control 0 day 12,100 ±25.3 0.22 ±0.001 35.6 ±1.5 1.28 ±0.11 0.39 ±0.01
7 days 12,850 ±28.6 0.22 ±0.001 36.6 ±1.05 1.35 ±0.09 0.40 ±0.02
14 days 13,250 ±22.5 0.25 ±0.01 37.1 ±0.74 1.4 ±0.07 0.41 ±0.01
0 day 63,370 ±644.9 0.05 ±0.003 68.9 ±7.89 2.49 ±0.23 0.64 ±0.03
Diabetic control 7 days 64,188 ±353.9 0.06 ±0.002 95.6 ±122 2.84 ±0.41 0.75 ±0.03
14 days 62,705 ±221.5 0.04 ±0.005 112.7 ±25.5 3.15 ±0.51 0.78 ±0.09
0 day 63,425 ±308.1 0.05 ±0.005 76.6 ±15.4 2.56 ±0.33 0.64 ±0.023
C,c 7 days 54,930 ±112.6* 0.10 ±0.004 70.2 ±19.1 1.35 ±0.35* 0.55 ±0.06
14 days 45,993 ±252.2** 0.18 ±0.003* 62.3 ±19.1* 1.02 ±0.40* 0.48 ±0.075*
0 day 63,312 ±144.3 0.05 ±0.005 78.1 ±4.4 2.66 ±0.33 0.68 ±0.02
Metformin 7 days 51,425 ±371.6** 0.13 ±0.003 66.4 ±7.7 1.76 ±0.33* 0.59 ±0.03
14 days 43,300 ±602.9*** 0.24 ±0.003* 59.1 ±3.9* 1.11 ±0.8* 0.51 ±0.04*
Values are mean ±S.E. Significance, * P\0.05, ** P\0.01, *** P\0.001
Med Chem Res
The plasma insulin levels in the C.c and metformin
treated groups were also increased, i.e., in the case of C.c
from an initial 0.039 to 0.166 lg/l and in the case of
metformin from an initial 0.041 to 0.186 lg/l after 14 days
of treatment.
Antidyslipidemic effect of C.c on high fructose fed
male Syrian golden hamsters
High fructose and high fat diet hamsters when treated with
C.c extract at the dose of 100 mg/kg b.w. declined their
Fig. 4 a,bEffect of
administration of C.c and
metformin on OGTT profiles of
STZ-induced diabetic rats on
day 7 (a) and 14 (b) post
treatment
Fig. 5 a,bEffect of C.c and
metformin on OGTT profile of
high fructose and high diet fed
rats on day 7th and 14th
Table 2 Effect on serum parameters after once daily repeated oral administration of C.c for 14 days in HFD ?low dose STZ-induced diabetic
rats
Groups Days OGTT
AUC ±SEM
Insulin
(lU/ml)
HOMA-IR TG
(mg/dl)
Chol
(mg/dl)
LDL-C
(mg/dl)
HDL-C
(mg/dl)
Normal sucrose diet 0 11,160 ±54.7 3.2 ±0.02 0.51 ±0.11 53.3 ±3.3 56.3 ±2.2 30.4 ±0.9 37.2 ±4.2
7 11,261 ±38.7 3.9 ±0.03 0.67 ±0.12 55.1 ±0.9 60.4 ±0.1 34.7 ±3.5 39.8 ±4.4
14 12,023 ±22.7 4.3 ±0.05 0.76 ±0.14 59.2 ±1.2 64.3 ±2.3 38.9 ±5.2 43.1 ±3.3
High fructose-high fat diet 0 18,277 ±11.3 5.8 ±0.11 1.75 ±1.2 222.3 ±9.9 96.2 ±8.6 45.5 ±4.1 38.2 ±3.2
7 19,421 ±23.1 6.6 ±0.22 2.2 ±0.98 235.1 ±2.1 99.6 ±3.1 48.1 ±2.2 31.1 ±1.1
14 18,987 ±11.3 6.8 ±0.18 2.5 ±0.89 241.3 ±1.9 100.2 ±2.2 49.1 ±3.1 30.3 ±4.4
High fructose-high fat
diet ?STZ Control
0 60,434 ±32.13 2.7 ±0.09 1.99 ±0.12 329.9 ±7.6 166.7 ±1.1 71.2 ±14.8 37.2 ±8.5
7 65,856 ±481.8 2.9 ±0.3 2.16 ±1.2 322.5 ±7.6 166.7 ±1.3 71.6 ±0.88 33.3 ±0.9
14 66,239 ±671.3 2.8 ±0.2 2.21 ±0.98 340.2 ±4.7 170.1 ±2.2 74.3 ±1.4 34.8 ±12
High fructose-high fat
diet ?STZ ?C.C
0 60,521 ±311.1 2.6 ±0.2 1.92 ±0.98 325.3 ±7.6 164.5 ±3.1 72.2 ±12.1 36.1 ±3.5
7 54,702 ±842.1* 2.2 ±0.9 1.18 ±0.99 292.7 ±3.4* 143.5 ±2.2* 67.8 ±0.60 37.1 ±0.93
14 48,600 ±615.9** 1.9 ±0.3* 0.77 ±0.83* 255.3 ±9.4* 132.2 ±1.6* 62.1 ±0.61* 38.6 ±0.71*
High fructose-high fat
diet ?STZ ?metfermin
0 60,331 ±301.5 2.8 ±0.1 2.08 ±0.90 326.3 ±2.1 162.1 ±1.3 71.4 ±2.1 34.1 ±0.89
7 52,071 ±485.1** 2.1 ±0.2 1.08 ±0.97 328.3 ±3.3 160.5 ±3.2 71.7 ±3.3 32.2 ±0.24
14 40,749 ±939.0*** l.8 ±0.98 0.64 ±0.89** 327.1 ±2.1 169.1 ±4.2 74.3 ±2.2 34.5 ±0.51
Values are mean ±S.E. Significance, * P\0.05, ** P\0.01, *** P\0.001
Med Chem Res
serum total cholesterol (22.7%), serum triglycerides
(21.0%), and LDL-cholesterol levels (16.9%) level and
elevated their HDL-cholesterol level (12.2%) (Fig. 7a).
Effect on a-glucosidase
C.c extract exerted inhibitory effect on alpha-glucosidase
by showing around 45% inhibition at the concentration of
100 lg/ml compared the acarbose which showed around
50% inhibition on alpha-glucosidase at 25.0 lg/ml
(Fig. 8a). The concentration-dependent effect of C.c
extract is shown in Fig. 8b.
Effect on aldose reductase
C.c extract was also found efficient in inhibiting aldose
reductase from eye lens of both normal and STZ-induced
diabetic rats. Table 4shows the % inhibition on aldose
reductase from eye lens of normal and diabetic rats at 1, 10
and 100 lg/ml concentration of C.c in the assay system.
Their IC
50
values were calculated to be around 4.75 and
7.70 lg/ml, respectively, in the case of aldose reductase
from normal and STZ-induced diabetic rats.
Discussion
The seeds of C. cyminum have been used as natural med-
icine since the Vedic glory. The present study was under-
taken to investigate the antihyperglycemic activity of
ethanolic extract of seeds of C. cyminum not only in nor-
moglycemic rats but also in validated models of type II
diabetes mellitus (STZ-induced diabetic rats; HFD ?low
dose STZ-induced diabetic rats; n2-STZ-induced diabetic
rats) and antidyslipidemic activity in male Syrian golden
hamsters.
In normoglycemic rats ethanolic extract exhibits gly-
caemic control by decreasing the peak blood glucose
(Fig. 1) and the area under OSTT curve. The return to
baseline glycaemic value, 2 h after the sucrose load which
is indicative of an enhanced glucose utilization which may
be triggered either by insulin production from the pancre-
atic bcells or by inhibiting the intestinal a-glucosidase
enzyme responsible for breakdown of polysaccharides
into its monomeric form and thus inhibit postprandial
hyperglycemia.
The single dose (65 mg/kg) of streptozotocin injection
can produce Diabetes mellitus by destroying the b-cells of
pancreas (Palmer et al., 1998). Streptozotocin, a cytotoxic
agent; enters the pancreatic b-cells via glucose transporter-
GLUT2; induces alkylation of DNA, release of nitric oxide
which ultimately results in destruction of pancreatic cell by
necrosis (Mythili et al., 2004). It is evident from the result
Table 3 Effect of C.c and metformin on neonatally streptozotocin treated rats on OGTT and insulin profiles
Groups Normal Control Diabetic Control C.c Metformin
Days 0 7 14 0 7 14 0 7 14 0 7 14
AUC ±SEM 11,600 ±22.1 12,150 ±18.1 13,080 ±20.1 42,489 ±103.3 43,485 ±109.7 48,671 ±291.5 42,461 ±118.1 38,955 ±145.8 35,168 ±193.8 42,473 ±122.8 33,386 ±140.5 32,048 ±144.2
Insulin 0.206 ±0.001 0.232 ±0.004 0.249 ±0.010 0.041 ±0.010 0.064 ±0.014 0.017 ±0.004 0.039 ±0.007 0.088 ±0.003 0.166 ±0.006* 0.041 ±0.006 0.091 ±0.002 0.186 ±0.004*
% Activity 10.4* 27.7** 23.2*** 34.1***
Values are mean ±S.E. Significance, * P\0.05, ** P\0.01, *** P\0.001
Med Chem Res
that there is gradual improvement over the experimental
period, with the maximal beneficial effect was observed at
the end of the experiment. In diabetes the hyperglycemia
also induces the elevation of plasma levels of urea, uric acid
and creatinine, which are considered as the significant
markers of renal dysfunction (Daisy et al., 2009, Mahalin-
gam and Kannabiran 2010). As shown in the Table 1there
is significant increase in the serum level of urea, uric acid,
and creatinine in the diabetic rats when compared with
respective normal control rats, while after the treatment of
diabetic rats with ethanolic extract of the C. cyminum seeds
the levels of urea, uric acid, and creatinine were signifi-
cantly (P\0.05) decreased. These results are in agreement
with other previous studies on the fruit extract of Terminalia
bellerica (Latha and Daisy, 2010), and roots of Hemidesmus
indicus (Mahalingam and Kannabiran, 2010).
Numerous studies have been reported on animal models
that mimic human diabetes. Generally, rats fed with high-
fat diet and STZ treatments have been used to develop
diabetic models (Srinivasan et al., 2005). However, the
type and percentage of fat used in diet formulation differ
from one study to another. In our experiments a diabetic rat
model was developed by injecting STZ (35 mg/kg) to rats
fed with high fructose (55%)-high fat diet (13%). High
Fig. 6 Effect of C.c and
metformin on OGTT of
neonatally streptozotocin-
induced diabetic rats on day 7
(a) and 14 (b)
Fig. 7 Effect of C.c on plasma lipids levels of high fructose high fat
diet fed male Syrian hamsters
Fig. 8 Effect of C.c and
acarbose on alpha-glucosidase
(a) and concentration-dependent
effect of C.c (b)
Table 4 Effect of C.c on aldose reductase (AR) from eye lens of
normal and STZ-induced diabetic rats
Source %Inhibition IC
50
(lg/ml)
100 lg/ml 10 lg/ml 1 lg/ml
Normal eye lens 75.69 56.06 25.92 4.73
Diabetic eye lens 65.51 56.77 20.71 7.70
Med Chem Res
fructose-high fat diet followed by low dose STZ injection
can be used to develop obese-diabetic rats that mimic
human diabetes in terms of obesity and impaired insulin
sensitivity. Impaired insulin sensitivity plays a pivotal role
in the development of diabetes (Buchanan, 2003). In our
obese-diabetic rat model the cause of hypertriglyceridemia
and hypercholesterolemia was different from that in STZ-
induced diabetic rats. In high fructose-high fat diet, fruc-
tose is mostly responsible for induction of dyslipidemia as
it bypasses the main regulatory steps causing continuous
production of PGA and Acetyl CoA resulting in hypertri-
glyceridemia and hypercholesterolemia (Frayan and
Kingman, 1995). On the other hand fat also plays an
important role in the development of obesity and insulin
resistance. As a result of feeding of high-fructose high-fat
diet for 4 weeks and low dose injection of Streptozotocin
(35 mg/kg) produces a model that is associated with
hyperglycemia, hyperinsulinemia, increased insulin resis-
tance index (HOMA), and dyslipidemia. The findings in the
present article reveals that feeding of ethanolic seed extract
of C. cyminum to high-fructose high fat fed rats, signifi-
cantly reversed the hyperglycemia, hyperinsulinemia and
insulin resistance index. The ethanolic extract of the seeds
of C. cyminum also improves the serum lipid profile
declining the levels of triglycerides, total cholesterol, LDL-
cholesterol along with increasing the level of HDL-cho-
lesterol as shown in Table 2. These results are in agreement
with other previous studies with the Cocoa extract (Mhd
Jalil et al., 2009), and rhizome of Zingiber officinale
(Nammi et al., 2009).
The neonatal-STZ treated rats are suitable model of type
II diabetes as it has potential advantage over others by
exhibiting the various stages of Type 2 diabetes mellitus
such as impaired glucose tolerance, mild, moderate and
severe hyperglycemia with alteration of dose and days of
STZ injection. The n-STZ rats’ exhibit slightly lowered
plasma insulin, slightly elevated plasma glucose levels and
lowered pancreatic insulin content (Arulmozhi et al.,
2009). The bcells in the n-STZ rats bear a resemblance to
the insulin secretory characteristics found in Type 2 dia-
betic patients (Portha et al., 1974). The results of the
present study indicate that n-STZ treated rats develop
moderate Type 2 diabetes when compared with normal
rats, however, animals shows gradual improvement in
plasma glucose level and plasma insulin level in compar-
ison to the control group as shown in Fig. 6and Table 3.
These results are in agreement with other previous studies
on the extract of Tournefortia hirsutissima (Andro-Cetto
et al., 2007), and Cassia glauca (Farswan et al., 2009).
The HFD-fed hyperlipidemic hamster model has earlier
been reported as an ideal in vivo model for testing anti-
dyslipidemic drugs (Bhatia et al., 2003). Twenty-days
feeding of high fat diet increases plasma triglycerides, total
cholesterol, LDL-cholesterol along with decrease in HDL-
cholesterol. Treatment with ethanolic extract of seeds of C.
cyminum caused significant lowering in plasma triglycer-
ides, total cholesterol and LDL-cholesterol. Our result also
shows that ethanolic extract increases the level of HDL-
cholesterol.
An abnormal increase in postprandial blood glucose
level is one of the characteristic feature and important goal
for the cure of Type II diabetes (Sunil et al., 2009).
a-glucosidase an enzyme which digests the carbohydrates
into its monomeric form therefore, its inhibition can cause
a delay in carbohydrate digestion and further its absorption
thus attenuates the postprandial hyperglycmic excursions.
It is also been reported that a-glucosidase inhibitors only
slows the carbohydrate digestion without altering the net
nutrient caloric value (Lee, 2005). The finding in the article
suggests that the ethanolic extract of seeds of C. cyminum
also possess a moderate a-glucosidase inhibitory property
which is one of the causes for gradual improvement in the
diabetic status during the experiments.
Eye lenses are one of the insulin-insensitive organ and
the target for the complications like cataract formation,
which is one of the late stage secondary complications of
type II diabetes (Ueda et al., 2004). It is evident from
results shown in Table 4and in Fig. 9, that the ethanolic
extract of seeds of C. cyminum also possesses an aldose
reductase inhibitory activity. The presence of aldose
reductase inhibitory property along with antidiabetic
properties is a good finding in the field of treatment of
diabetes mellitus because presently most of the antidiabetic
drug attenuates hyperglycemia without any satisfactory
effect towards the later stage secondary complications.
The effect of ethanolic seed extract of C. cyminum on
these validated models of diabetes and dyslipidemia proved
that it has good antihyperglycemic and antidyslipidemic
properties.
Fig. 9 % inhibition of AR activity on normal and diabetic eye lenses
by C.c
Med Chem Res
Acknowledgment The authors gratefully acknowledge to CSIR,
New Delhi for providing financial support to carry out this work in the
form of network project (NWP-0032).
References
Mhd Jalil AM, Amin Ismail A, Chong PP, Hamid M, Hasbullah Syed
Kamaruddin S, Hasbullah S, Kamaruddin S (2009) Effect of
cocoa extract containing polyphenols and methylxanthines on
biochemical parameters of obese-diabetic rats. J Sci Food Agri
89:130–137
Andro-Cetto A, Revilla-Monsalve C, Wiedenfeld H (2007) Hypogly-
cemic effect of Tournefortia hirsutissima L., on n-streptozotocin
diabetic rats. J Ethnopharmacol 112:96–100
Andrade-Cetto A, Revilla-Monsalve C, Wiedenfeld H (2007) Hypo-
glycemic effect of Tournefortia hirsutissima L., on n-streptozo-
tocin diabetic rats. J Ethnopharmacol 112:96–100
Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL (2009) Neonatal
streptozotocin-induced rat model of Type 2 diabetes mellitus: a
glance. Indian J Pharmacol 36(4):217–221
Bhatia G, Rizvi F, Saxena R, Puri A, Khanna AK, Chander R, Wulf
EM, Rastogi AK (2003) In vivo model for dyslipidemia with
diabetes mellitus in hamsters. Indian J Exp Biol 41:1456–1459
Buchanan TA (2003) Pancreatic beta-cell loss and preservation in
type 2 diabetes. Clin Ther 25(Suppl B):B32–B46
Daisy P, Vargese L, Priya EC (2009) Comparative studies on the
different leaf extracts of Elephantopus scaber L. on STZ-
induced diabetic rats. Eur J Sci Res 32(3):304–313
de la Fuente JA, Manzanaro S (2003) Aldose reductase inhibitors
from natural sources. Nat Prod Rep 20:243–251
Dhandapani S, Subramanian VR, Rajagopal S, Namasivayam N
(2002) Hypolipidemic effect of Cuminum cyminum L. on alloxan
induced diabetic rats. Pharmacol Res 46(3):251–255
Farswan M, Majumder MP, Percha V (2009) Protective effect of
Cassia glauca Linn. On the serum glucose and hepatic enzymes
level in streptozotocin induced NIDDM in rats. Indian J
Pharmacol 41(1):19–22
Frayan NK, Kingman MS (1995) Dietary sugars and lipid metabolism
in humans. Am J Clin Nutr 62(suppl):250S–263S
Hayman S, Kinoshita JH (1965) Isolation and properties of lens
Aldose reductase. J Biol Chem 240:877–882
Joshi SG (2000) Medicinal plants: family Apiaceae, 1st edn. Oxford
and IBH Publishing Co. Pvt. Ltd, New Delhi, pp 34–35
Khare CP (2004) Indian medicinal plants. ISBN: 978-0-387-70637-5
Springer-Verlag, Berlin/Heidelberg
Kubo I, Kinst-Hori I (1998) Tyrosinase inhibitors from cumin. J Agric
Food Chem 46:5338–5341
Latha RCR, Daisy P (2010) Influence of Terminalia bellerica Roxb.
Fruit extracts on biochemical parameters in streptozotocin
diabetic rats Int J Pharmacol 6(2):89–96
Lebovitz HE (1997) Alpha glucosidase inhibitors. Endocrinol Metab
Clin North Am 26(3):539–551
Lee H-S (2005) Cuminaldehyde: aldose reductase and a-glucosidase
inhibitor derived from Cuminum cyminum L. seeds. J Agric Food
Chem 53:2446–2450
Lee SH, Kim MK (2001) Rat intestinal a-glucosidase and lens aldose
reductase inhibitory activities of grain extract. Food Sci
Biotechnol 10:172–177
Lowry HO, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein
measurement with the folin phenol reagent. J Bio Chem 193:
265–275
Mahalingam G, Kannabiran K (2010) 2-Hydroxy 4-methoxy benzoic
acid isolated from roots of Hemidesmus indicus ameliorates
liver, kidney and pancreas injury due to streptozotocin-induced
diabetes in rats. Indian J Exp Biol 48:159–164
Mlinar B, Marc J, Janez A, Pfeifer M (2007) Molecular mechanism of
insulin resistance an associated diseases. Clin Chim Acta
375:20–35
Mythili MD, Vyas R, Gunasekaram S (2004) Effect of streptozotocin
on the ultrastructure of rat pancreatic islets. Microsc Res Tech
63:274–281
Nammi S, Sreemantula S, Roufogalis BD (2009) Protective effect of
ethanolic extract of Zingiber officinale rhizome on the develop-
ment of metabolic syndrome in high-fat diet-fed rats. Basic Clin
Pharmacol Toxicol 104(5):366–373
Narender T, Puri A, Sweta, Khalid T, Saxena R, Bhatia G, Chandra R
(2006) 4-Hydroxyisoleucine an unusual amino acid as antidy-
slipidemic and antihyperglycemic agent. Bioorg Med Chem Lett
16:293–296
Palmer AM, Thomas CR, Gopaul N, Dhir S, Anggared EE, Poston L
(1998) Dietary antioxidant supplementation reduces lipid per-
oxidation but impairs vascular function in small mesenteric
arteries of streptozotocin diabetic rat. Diabetologia 41:148–156
Portha B, Levancher C, Picolon L, Rosselin G (1974) Diabetogenic
effect of streptozotocin in the rat during the prenatal period.
Diabetes 23:883–895
Ravinet TC, Delgorge C, Menet C, Arnone M, Soubrie P (2004) CB
1
cannabinoid receptor knockout in mice leads to leanness,
resistance to diet-induced obesity and enhanced leptin sensitiv-
ity. Int J Obes Relat Metab Disord 28:640–648
Roman-Ramos R (1995) Antihyperglycemic effect of some edible
plants. J Ethnopharmacol 48:25–32
Somwar R, Sweeny G, Ramlal T, Klip A (1998) Stimulation of
glucose and amino acid transport and activation of the insulin
signaling pathways by Insulin lispro in L6 skeletal muscle cells.
Clin Ther 20:125–140
Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P (2005)
Combination of high-fat diet-fed and low dose streptozotocin-
treated rat: a model for type 2 diabetes and pharmacological
screening. Pharmacol Res 52:313–320
Sultana S, Ripa FA, Hamid K (2010) Comparative antioxidant
activity study of some commonly used spices in Bangladesh. Pak
J Biol Sci 13(7):340–343
Sung BK, Lee CH, Kim CH, Lee HS (2004) Antimite effect of
essential oils derived from 24 Rosaceae and Umbelliferae
species against stored food mite. Food Biotechnol 13:512–515
Sunil C, Latha G, Mohanraj P, Kalichelvan K, Agastian P (2009)
a-Glucosidase inhibitory and antidiabetic activities of ethanolic
extract of Pisonia alba Span. leaves. Int J Integrative Biol 6(1):
41–45
Tiwari P, Rahuja N, Kumar R, Lakshmi V, Srivastava NM, Agarwal
SC, Raghubir R, Srivastava AK (2008) Search for antihyper-
glycemic activity of few marine flora and fauna. Indian J Sci
Technol 1(5):1–5
Tripathi KB, Srivastava KA (2006) Diabetes mellitus: complications
and therapeutics. Med Sci Monit 12(7):130–147
Ueda H, Kuroiwa E, Tachibana Y, Kawanihi K, ayala F, Moriyasu M
(2004) Aldose reductase inhibitors from the leaves of Myrciaria
duba (H.B.&K.) McVaugh. Phytomedicine 11:652–665
Watanabe J, Kawabata J, Kurihara H, Niki R (1997) Isolation
and identification of a-glucosidase inhibitors from Tochucha
(Eucommia ulmoides). Biosci Biotechnol Biochem 61:177–178
Med Chem Res
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