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Anti-hyperglycaemic and anti-dyslipidaemic effect of dietary supplement of white Ocimum Sanctum Linnean before and after STZ-induced diabetes mellitus

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  • College of Pharmacy, Rangsit University

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This study was conducted to elucidate whether dietary treatment of white Ocimum sanctum Linnean. (OS) either before or after streptozotocin (STZ) - induced diabetes has anti-hyperglycemic and anti-dyslipidaemic action. Two series of experiments were performed. The first involved three groups of rats; one group was fed normal diet for 6 weeks, a second diabetic group received normal diet and a third diabetic group received 2 % dietary OS from 3 weeks after induction of diabetes for a period of 3 weeks. The second involved three groups of rats: one group was fed normal diet, a second group received or did not receive 2 % dietary white OS before induction of diabetes. Fasting blood glucose was determined before and after induction of diabetes. At the end of the study, arterial blood was collected to evaluate serum triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and creatinine. The results show that blood glucose was not significantly altered after 3 weeks of dietary supplement of white OS in diabetic rats. In contrast, elevated blood glucose after 3 weeks of diabetes was alleviated in diabetic rats pretreated with white OS. STZ-induced diabetes significantly raised serum triglyceride, total cholesterol, LDL-cholesterol, AST, ALT and creatinine. White OS supplementation, either before or after induction of diabetes, normalized lipid profile and creatinine and partially reduced an elevated serum AST and ALT. It can be concluded that STZ-induced hyperglycaemia can be ameliorated by pretreatment with white OS. Dietary supplement with OS either before or after diabetic induction reverses dyslipidaemia and renal glomerular filtration function, and partially protects liver function.
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Int. J Diabetes & Metabolism (2005) 13: 18-23
18
Anti-hyperglycaemic and anti-dyslipidaemic effect of dietary supplement of
white Ocimum Sanctum Linnean before and after STZ-induced diabetes
mellitus
Thamolwan Suanarunsawat1* and Thanapat Songsak2
Physiology Unit, Department of Medical Sciences, Faculty of Sciences, Rangsit University, Paholyotin Rd.,Thailand,
120001Department of Pharmacognosy, Faculty of Pharmacy, Rangsit University, Paholyotin Rd.,Thailand, 120002
________________________________________________________________________________________________________
Abstract
This study was conducted to elucidate whether dietary treatment of white Ocimum sanctum Linnean. (OS) either before or after
streptozotocin (STZ) - induced diabetes has anti-hyperglycemic and anti-dyslipidaemic action. Two series of experiments were
performed. The first involved three groups of rats; one group was fed normal diet for 6 weeks, a second diabetic group received
normal diet and a third diabetic group received 2 % dietary OS from 3 weeks after induction of diabetes for a period of 3 weeks.
The second involved three groups of rats: one group was fed normal diet, a second group received or did not receive 2 % dietary
white OS before induction of diabetes. Fasting blood glucose was determined before and after induction of diabetes. At the end
of the study, arterial blood was collected to evaluate serum triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol,
serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and creatinine. The results show that blood
glucose was not significantly altered after 3 weeks of dietary supplement of white OS in diabetic rats. In contrast, elevated blood
glucose after 3 weeks of diabetes was alleviated in diabetic rats pretreated with white OS. STZ-induced diabetes significantly
raised serum triglyceride, total cholesterol, LDL-cholesterol, AST, ALT and creatinine. White OS supplementation, either before
or after induction of diabetes, normalized lipid profile and creatinine and partially reduced an elevated serum AST and ALT. It
can be concluded that STZ-induced hyperglycaemia can be ameliorated by pretreatment with white OS. Dietary supplement with
OS either before or after diabetic induction reverses dyslipidaemia and renal glomerular filtration function, and partially protects
liver function.
Key words: diabetes mellitus, serum lipid, Ocimum sanctum Linnean.
Introduction
Diabetes mellitus (DM) is a serious metabolic disease which
has several complications including diabetic nephropathy,
diabetic neuropathy, coronary heart disease and hypertension.1
It has been estimated that by the year 2010, the prevalence of
DM worldwide will reach approximately 240 million.2
Patients with DM are more likely to develop and die from
microvascular and macrovascular complications than the non-
diabetic population.3 There is usually an association between
coronary heart disease or atherosclerosis and dyslipidaemia.4,5
Dyslipidaemia is a frequent complication of DM and is
characterized by low levels of HDL-cholesterol and high
levels of LDL-cholesterol and triglyceride. Several groups of
hypoglycaemic drugs are currently available to treat DM.
However, their toxic side effects and sometimes diminution in
response after prolonged use are problematic. Management of
______________________________
Correspondence to: Thamolwan Suanarunsawat, Physiology Unit,
Department of Medical Sciences, Faculty of Sciences, Rangsit University,
Praholyothin Rd., Thailand, 12000. Tel : 662-9972222 ext 1473, Fax : 662-
9972222 ext 1417, e-mail : thamolwa@rangsit.rsu.ac.th
DM to avoid these problems is still a major challenge. There
is an ongoing search for natural products with anti-
hyperglycaemic and anti-dyslipidaemic activities with
minimal side effects. There are several kinds of medicinal
plants in Thailand which have been reported to exert anti-
hyperglycaemic and/or anti-dyslipidaemic actions.6 Among
them, Ocimum sanctum Linnean. (OS) is very promising since
it is routinely used as a vegetable and also for the treatment of
DM by local people in various countries including India and
Thailand. Several studies have demonstrated that OS
possesses anti-hyperglycaemic and/or anti-dyslipidaemic
effect in normal and DM animals.7-10 Preliminary studies in
our laboratory have shown that white OS exerts hypoglycemic
action in normal rats whereas red OS was without this effect.
We have investigated whether supplementation of diet with
white OS can retard dyslipidaemia and hyperglycaemia in
diabetes.
Materials and methods
Animal preparation
Male Wistar rats weighing between 180-220 g from Animal
Center, Salaya Campus, Mahidol University, were used in the
Suanarunsawat & Songsak
19
Table 1: Changes in body weight, food intake and fasting blood glucose in rats fed with or without white Ocimum sanctum Linnean. (OS)
during the last three weeks of the study.
Before feeding with or without OS After feeding with or without OS
1 wk 3 wk 1 wk 3 wk
Body weight (g)
Group 1 200.00 ± 3.32 274.00 ± 5.05 300.86 ± 8.02** 351.14 ± 10.69***
Group II 212.57 ± 4.73 221.71 ± 6.55 233.14 ± 7.23* 231.14 ± 6.95*
Group III
180.86 ± 4.20 194.57 ± 4.48 196.57 ± 4.47 213.43 ± 6.19**
Food Intake (g/24 hr)
Group 1 20.57 ± 1.36 22.29 ± 2.28 22.29 ± 2.69 24.14 ± 1.35
Group II 35.00 ± 3.31 41.86 ± 2.62 43.71 ± 1.30 45.86 ± 1.10
Group III
35.28 ± 3.04 37.43 ± 2.24 37.86 ± 2.20 37.14 ± 2.99
Blood glucose (mg/dl)
Group 1 84.71 ± 3.01 99.00 ± 4.92 105.14 ± 4.05 100.43 ± 1.66
Group II 250.71 ± 19.20 318.14 ± 24.18 310.86 ± 25.20 357.28 ± 26.30
Group III
230.29 ± 28.47 279.28 ± 23.08 305.86 ± 27.82 326.00 ± 28.46
Values are shown as mean ± SEM.
group I = normal control rats , group II = diabetic rats fed normal diet, group III = diabetic rats fed with white Ocimum sanctum Linnean.
* significant difference comparing to the third week before white OS treatment (*P<05, **P<0.01, ***P<0.001).
Table 2: Changes in serum lipid profile, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and serum creatinine
(Cr) in rats fed with or without white Ocimum sanctum Linnean. during the last three weeks of this study.
Group I Group II Group III
Triglyceride (mg/dl) 95.62 ± 11.49 219.02 ± 24.99* 108.98 ± 14.88 #
Total Cholesterol (mg/dl) 86.29 ± 8.48 208.27 ± 32.65*** 97.84 ± 6.52 #
HDL Cholesterol (mg/dl) 46.86 ± 5.79 39.36 ± 3.59 50.76 ± 3.51
LDL Cholesterol (mg/dl) 27.84 ± 1.97 41.76 ± 4.61* 27.56 ± 3.54#
AST(unit/L) 30.79 ± 2.16 57.50 ± 4.07* 45.79 ± 3.72a
ALT (unit/L) 23.00 ± 2.68 60.71 ± 3.83*** 44.29 ± 4.55#b
Cr (mg/dl) 1.04 ± 0.04 1.96 ± 0.18** 1.21 ± 0.08##
Data are presented as mean ± SEM
Abbreviations for each group are shown in table I
* significant difference comparing to group I (* P<0.05 , ** P<0.01 ,*** P<0.001).
# significant difference comparing to group II (# P< 0.05 , ## P<0.01 )
a ,b significant difference comparing to group I at P< 0.05 and P<0.01 respectively
study. Rats were housed in a 12-hr light-dark cycle at 25 ± 2
°C and fed normal rat food and tap water ad libitum. All
animals were cared for in accordance with the principles and
guidelines of the Institutional Animal Ethics Committee of
Rangsit University, which is under The National Council of
Thailand for Animal Care. Induction of diabetes was carried
out by intraperitoneal injection of STZ (Sigma, St Louis, MO,
USA) dissolved in citrate buffer pH 4.5 at a dose of 70 mg/kg
bodyweight. Two days after STZ injection blood glucose was
measured and only those rats with fasting blood glucose >170
mg/dl were included in the study
Preparation of white Ocimum sanctum Linnean
Fresh leaves of white OS obtained from The Ministry of
Public Health, Thailand, were washed in tap water and then
left to dry at room temperature for 2-3 days. The dried leaves
were then ground to fine powder in a mixer. The dried leaf
powder was then added to the diet to makeup 2 % of the diet.
Experimental design
Two series of experiments were performed.
Series I: The effect of dietary supplement of white OS on
blood glucose and serum lipid 3 weeks after induction of
diabetes
Three groups of 7 rats were used as follows:
Group I: Control rats fed with normal diet for 6 weeks. The
normal diet contained protein 23.5 %, fat 4.4 %, fibre 4.9 %,
mineral and vitamin 6.4 %, moisture 12 % and carbohydrate
46.8 % with added corn starch 2 %.
Group II: Diabetic rats fed with normal diet throughout 6
weeks.
Group III: Diabetic rats fed with normal diet for 3 weeks and
then switched to normal diet with 2 % white OS which
replaced the corn starch.
Body weight, food consumption and fasting blood glucose
were determined at the first and third week after the start of
Antihyperglycaemic and anti-dyslipidaemic effect of white Ocium Sanctum Linnean
20
Table 3 The alterations of body weight, food intake and fasting blood glucose in rats pretreated with or without white Ocimum sanctum
Linnean. (OS) for three weeks before diabetic induction.
Before induction of Diabetes After induction of Diabetes
1 wk 3 wk 1 wk 3 wk
Body weight (g)
Group A 200.00 ± 3.32 274.00 ± 5.05 300.86 ± 8.02** 351.14 ± 10.69***
Group B 193.83 ± 2.76 238.00 ± 1.89 231.003.68 232.67 ± 4.28
Group C
198.00 ± 5.93 249.67 ± 6.39 240.00 ± 7.90 245.67 ± 11.51
Food Intake (g/24 hr)
Group A 20.57 ± 1.36 22.29 ± 2.28 22.29 ± 2.69 24.14 ± 1.35
Group B 23.83 ± 1.19 28.00 ± 1.63 24.83 ± 2.36 48.83 ± 5.57**
Group C
27.00 ± 2.57 28.83 ± 2.55 24.33 ± 4.68 38.83 ± 1.14*
Blood glucose (mg/dl)
Group A 84.71 ± 3.01 99.00 ± 4.92 105.14 ± 4.05 100.43 ± 1.66
Group B 89.67 ± 1.64 90.83 ± 1.00 260.50 ± 14.37*** 336.33 ± 10.76***
Group C
85.67 ± 4.37 89.00 ± 1.17 211.83 ± 24.36** 243.67 ± 29.29**a
Values are given as mean ± SEM.
group A = normal control rats.
group B = diabetic rats without white Ocimum sanctum Linnean pretreatment
group C = diabetic rats with white Ocimum sanctum Linnean pretreatment and continued until end of experiment
* significant difference comparing to the third week before diabetic induction (*P<0.05 , **P<0.01, *** P<0.001)
a significant difference comparing to group B at the same period at P< 0.05
Table 4 Changes of serum lipid profile, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and serum creatinine
(Cr) in rats pretreated with or without white Ocimum sanctum Linnean (OS) for 3 weeks before induction of diabetes.
Group A Group B Group C
Triglyceride (mg/dl) 95.62 ± 11.49 224.37 ± 17.97*** 114.49 ± 20.31##
Total Cholesterol (mg/dl) 86.29 ± 8.48 114.72 ± 5.60* 74.96 ± 6.79##
HDL Cholesterol (mg/dl) 46.86 ± 5.79 40.19 ± 2.07 39.08 ± 3.12
LDL Cholesterol (mg/dl) 27.84 ± 1.97 40.39 ± 1.23** 34.26 ± 2.06#
AST unit/L 30.79 ± 2.16 72.58 ± 3.22*** 40.29 ± 2.39####a
ALT (unit/L) 23.00 ± 2.68 63.17 ± 1.92 *** 38.57 ± 4.77 ####a
Cr (mg/dl) 1.04 ± 0.04 1.93 ± 0.25*** 0.88 ± 0.07##
Data are presented as mean ± SEM
Abbreviations for each group are shown in table 2
* significant difference comparing to group A (*P<0.05 , ** P<0.01, *** P<0.001)
#,##,### significant difference comparing to group B at P<0.05, P<0.01 and P<0.001 respectively.
a significant difference comparing to group A at P<0.05.
the study. After 1 and 3 weeks of either white OS or normal
diet treatment, body weight, food consumption and fasting
blood glucose were again measured. At the end of the
experiments rats were fasted overnight and then arterial blood
was collected from abdominal aorta to determine serum lipid
profile (triglyceride, cholesterol, HDL-cholesterol and LDL-
cholesterol). To determine whether dietary supplementation
with white OS affects liver and kidney function, serum
aspartate aminotransferase (AST), serum alanine
aminotransferase (ALT) and serum creatinine were measured.
Series II: Effect of pretreatment with white OS on blood
glucose and serum lipid in diabetic rats
Three groups of seven rats each were used as follows:
Group A: Control rats treated with normal diet for 6 weeks.
Group B: Rats were fed with normal diet for 3 weeks, and
then injected with STZ. Normal diet was supplied for
remainder of the study.
Group C: As for Group B except 2 % of white OS in diet was
provided both before and after induction of diabetes.
In order to prevent experimental error owing to STZ injection
in group B and C, only rats with fasting blood glucose >140
mg/dl were included in the study.
Body weight, food intake and fasting blood glucose were
determined at the first and third week after the beginning of
the experiment, and then again after 1 and 3 weeks of
diabetes. At the end of the experiment rats were fasted
Suanarunsawat & Songsak
21
overnight and blood was collected from the abdominal aorta
to determine serum lipid profile, AST, ALT and creatinine.
Biochemical assay
Fasting blood glucose was determined by blood glucose strip
(Medisense UK Ltd, Abbott Lab, UK). Serum lipid profile,
creatinine, AST and ALT were determined using an
enzymatic kit (Human, Gesellschaft Für Biochemica und
Diagnostica mbH, Germany)
Data and Statistical Analysis
Data are presented as mean ± SEM. The results were
analyzed for statistical significance by ANOVA using SPSS
version 10. Significant difference was accepted at the P <
0.05.
Results
Effect of dietary supplement of white OS on blood glucose
and serum lipid after 3 weeks of diabetes
Table 1 shows the changes in body weight, food intake and
fasting blood glucose in the rats before and after being fed
with either normal diet or diet with white OS after 3 weeks.
There was no significant change in food intake and blood
glucose in both groups of diabetic rats with or without white
OS. Also, no significant difference in blood glucose was noted
in both groups of diabetic rats with or without white OS.
Serum lipid profiles of rats with or without white OS during
the last 3 weeks are shown in Table 2. Triglyceride and total
cholesterol were significantly raised from 95.62 ± 11.49 and
86.29 ± 8.48 in normal control to 219.02 ± 24.99 (P < 0.05)
and 208.27 ± 32.65 mg/dl (P < 0.01), respectively in diabetic
rats fed normal diet. Three weeks of dietary supplementation
of white OS to diabetic rats returned the high level of both
triglyceride and cholesterol to a level that was not significant
by difference from normal control rats (108.98 ± 14.88 and
97.84 ± 6.52 mg/dl, respectively). HDL-cholesterol was
lowered in diabetic rats (39.36 ± 3.59) but the level was not
significant by difference from normal control rats (46.86 ±
5.79). White OS feeding to diabetic rats slightly raised HDL-
cholesterol but the magnitude was not statistically significant
by difference from normal diabetic rats. The elevation of
LDL-cholesterol in normal diabetic rats (41.76 ± 4.61 mg/dl)
was normalized after 3 weeks of white OS supplementation (P
<0.05). White OS supplementation alleviated an augmentation
of both serum AST and ALT but the level remained higher
than that of normal control rats. White OS feeding reduced an
elevation of serum creatinine in diabetic rats fed normal diet
(1.96 ± 0.18 mg/dl) to the level that was statistically not
significantly different from normal control rats (1.21 ± 0.08
mg/dl).
Effect of pretreatment of dietary white OS on blood glucose
and serum lipid in diabetic rats
The alterations of body weight, food intake and blood glucose
in rats pretreated with or without white OS before diabetic
induction are illustrated in Table 3. Although there was no
significant change in body weight there was an increased
food intake after the onset of diabetes. Blood glucose was
significantly raised from 90.83 ± 1.00 to 260.50 ± 14.37 mg/dl
(P < 0.001) and 89.00 ± 1.17 to 211.83 ± 24.36 mg/dl (P <
0.01) one week after STZ injection in rats pretreated with or
without white OS, respectively. There was only one rat from
each group of diabetic rats in which fasting blood glucose was
lower than 140 mg/dl after STZ injection and hence, was
excluded from the study. The magnitude of blood glucose
elevation after 1 week of STZ injection in rats pretreated with
white OS was slightly lower than that of another group but the
level was not statistically significantly different. Three weeks
after induction of diabetes, blood glucose in rats pretreated
with white OS was significantly lower than that of diabetic
rats without white OS treatment (P <0.05).
Similar to the first series of experiments, pretreatment with
white OS for 3 weeks before induction of diabetes reduced
the elevated levels of triglyceride, total cholesterol and LDL-
cholesterol to a level which was statistically not significantly
different from normal control rats (table 2). Pretreatment
with white OS for 3 weeks before induction of diabetes
alleviated an augmentation of AST, ALT and normalized
serum creatinine.
Discussion
Ocimum sanctum Linnean (OS) is a medicinal plant
distributed mainly in the tropical and subtropical regions
including Thailand. Besides being widely used as a vegetable
it has also been used as an indigenous medicine in several
other countries in Asia and Africa11, particularly for its
hypoglycaemic and anti-dyslipidaemic effects in diabetes.7-10
However, these effects were displayed only in very short-term
studies. However, DM is a chronic disease and most diabetic
patients do not know whether they are diabetic until
symptoms such as diuresis, polydipsia, polyphagia present
themselves.
Whether OS normalizes dyslipidaemia and/or hyperglycaemia
after longer periods of diabetes is not known. From the
present results, 3 weeks of dietary supplement with white OS
to the rats after induction of diabetes for 3 weeks, had no
significant effect on blood glucose. This experimental result
was quite different from other studies7,12 which showed a
glucose-lowering action of OS. This inconsistency of data
could be for a variety of reasons. The study of Vats et al12 and
Chattopadhyay and his colleagues7 orally fed diabetic rats
with the aqueous extract of OS leaves whereas dietary
supplement of crude OS leaves was used in our study. The
aqueous extract of OS may have much more active ingredients
than crude dry leaves. However, it is quite difficult to mix
extracts of OS into the diet since it was a thick paste and is
sticky in nature. Furthermore, daily oral feeding with the
aqueous extract of OS for 3 weeks was likely to be stressful to
the rats. Of particular interest is that oral feeding of the
aqueous extract of OS begun during an early period after STZ
Antihyperglycaemic and anti-dyslipidaemic effect of white Ocium Sanctum Linnean
22
or alloxan injection whereas it was given after induction of
diabetes for 3 weeks in the present study. Moreover it has
been shown that hypoglycemic activity of aqueous extract of
OS is different in rats with different degrees of
hyperglycaemia induced by STZ or alloxan injection. The
greater the degree of hyperglycaemia the lesser the
hypoglycemic effect of aqueous extract of OS.12,13 In this
study, the blood glucose level in diabetic rats before white OS
treatment was approximately 300 mg/dl whereas in other
studies it was 140-300 mg/dl. It has been suggested that the
anti-hyperglycaemic effect of OS is at least partially
dependent on insulin release from β–cells as shown by a
greater anti-hyperglycaemic activity in mild hyperglycaemia
and lower response in moderate hyperglycaemia.13 Prolonged
hyperglycaemia along with severe hyperglycaemia as
occurred in the present study, may be the cause of failure of
glucose lowering action of OS.
Though dietary supplementation of white OS after induction
of diabetes had no glucose lowering effect, it reduced
hyperglycaemia in rats pretreated with white OS. The reason
why pretreatment with white OS in diabetic rats resulted in
the reduction of hyperglycaemia and treatment with white OS
3 weeks after induction of DM is unclear. It may be that
pretreatment of white OS before induction of diabetes caused
a gradual accumulation of active ingredients which may have
been enough to act against STZ-induced β-cells causing
damage by increasing islet superoxide dismutase activity,14
and then alleviating hyperglycaemia after STZ injection.
One of the most critical complications of DM is
atherosclerosis and coronary heart disease which are the result
of abnormal lipid metabolism.4 It has been reported that the
lipid profile of DM is characterized by low levels of HDL-
cholesterol, and elevated LDL-cholesterol and triglyceride
levels.4,15 This combination is often termed diabetic
dyslipidaemia. LDL carries cholesterol from the liver to the
peripheral cells and smooth muscle cells of arteries. A rise in
LDL may cause deposition of cholesterol in arterial walls and
hence promote atherosclerosis and coronary heart disease. In
the present study, not only pre-treatment but also post-
treatment with white OS normalized dyslipidaemia in diabetic
rats. This observation indicates that dietary supplement of
white OS either before or after induction of diabetes may be
effective at preventing and/or ameliorating atherosclerosis and
coronary heart disease. It is interesting to note that dietary
supplementation with white OS exerted different effects on
blood glucose but showed the same effect on lipid profile.
This indicates that recovery of dyslipidaemia in diabetic rats
treated with white OS is independent of blood glucose levels
and that glucose lowering activity and anti-dyslipidemic
activity may be provided by different active ingredients in OS.
OS leaves have been reported to contain several chemicals
including ursolic acid, apigenin, luteolin, orientin,
moludistin.16 It is widely known that OS leaves are rich in
essential oils, particularly eugenol.17 Currently no
experimental data has clearly supported an anti-
hyperglycaemic and anti-dyslipidemic mechanism for white
OS. Moreover, it is not clear which of its constituents or
combination of these constituents are responsible for the anti-
hyperglycemic and anti-dyslipidaemic effects.
In the living system, the liver and kidney are highly sensitive
to toxic or foreign agents. It is widely known that renal
glomerular capillaries and hepatic cells damage are often
found in DM. To assess experimental liver damage, serum
AST and ALT, which are more abundant in liver, were
determined. It was observed that dietary supplementation
with white OS either before or after induction of diabetes
partially reversed elevated serum AST and ALT, implying
that the magnitude of hepatic cell damage was reduced.
Eugenol, a major essential oil in OS, may contribute to this
action since it has been shown that oral administration of
eugenol reduced iron-induced hepatic damage.18 Dietary
treatment of OS also normalized a high level of serum
creatinine in diabetic rats, indicating its protective effect on
renal glomerular filtration ability.
In summary, dietary supplementation with white OS for 3
weeks after 3 weeks of diabetes had no significant effect on
blood glucose. In contrast, pre-treatment with white OS for 3
weeks before induction of diabetes reduced STZ-induced
hyperglycaemia. Dietary treatment of white OS either before
or after induction of diabetes significantly reduced the
elevated serum lipid profile, serum enzyme AST, ALT and
creatinine. The findings from this study indicate that STZ-
induced hyperglycaemia can be ameliorated by pre-treatment
with white OS. Dyslipidaemia is normalized in diabetic rats
supplemented with white OS either before or after induction
of diabetes. White OS also partially protects hepatic cell
damage and reverses renal glomerular filtration dysfunction in
diabetic rats.
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... It has been concluded that 2% of dried OS leaf powder can affect serum lipid profile favourably in diabetic rats. 7 Studies have also shown that OS leaf extract can also protect liver from heavy metals and prevent isoproterenol induced myocardial necrosis in rats. 8,9 Metformin is first line drug for newly diagnosed type 2 diabetes mellitus patients. ...
... 22 Suanarunsawat T et al, concluded that Ocimum decreased the high serum lipid profile and hepatic lipid content during high fat diet feeding in rats for seven weeks. 7 Present study also exhibited this. The lipid lowering effect is probably due to the rise of bile acid synthesis using cholesterol as a precursor. ...
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Background: Dyslipidaemia is an important risk factor for development of macrovascular complications in type 2 diabetes mellitus. Ocimum sanctum (OS) and metformin have shown to have antihyperlipidaemic effects. The present study was undertaken to evaluate the effects of OS and Metformin on body weight & plasma lipid levels of high fat diet fed diabetic ratsMethods: Total of 30 male wistar rats (100-150gm) were obtained. Animals were fed with a high fat diet throughout the study (6 weeks). Diabetes was induced by using single intra-peritoneal injection of Streptozotocin 50mg/kg at the end of 4 weeks. Diabetic rats were divided into groups of 6 each and treated as follows: Group 1- Diabetic control, was given vehicle orally. Group 2- O.S. ethanolic extract 100mg/kg body weight orally for 14 days. Group 3- O.S. ethanolic extract 200mg/kg body weight orally for 14 days. Group 4- Metformin 100mg/day for 14 daysResults: At the end of 4 weeks, body weight of rats were significantly increased (p <0.05). Maximum weight gain was seen in control group whereas weight gain was least in O.S. 200mg/kg group (p >0.05). Decrease in body weight was seen in metformin group. Abdominal circumference of rats also showed similar pattern (p >0.05). OS 200 caused significant reduction in serum LDL levels (p <0.05) and significant rise of serum HDL levels (p <0.05) as compared to control group. Metformin also favourably affected the lipid profile and its effects were not significantly different from effects of OS 200 (p> 0.05).Conclusions: Present study revealed that Ocimum Sanctum caused significant reduction in serum lipid levels in high fat diet fed diabetic rats. Metformin also exhibited antihyperlipidaemic activity. So, it is concluded that OS or metformin alone or in combination could be a novel adjunct to diet and life style modification for the management of dyslipidaemia in type 2 diabetes. Further studies are required to confirm the antidyslipidaemic activities of individual phytoconstituents of Ocimum sanctum.
... The species O. sanctum is a small herb, native to tropical and subtropical regions. It is often referred to as Holy or Tulsi Basil in the English and India (6). The chemical composition and antioxidant activity of O. sanctum essential oil (EO) have been investigated in previous studies. ...
... It has been reported that O. sanctum EO showed significant radical scavenging activity (10). Also, Suanarunsawat et al. (6) reported that O. sanctum decreases the high levels of thiobarbituric acid reactive substances in the cardiac tissue. Furthermore, administration of O. sanctum EO for 4 weeks in cholesterol fed rabbits significantly decreased serum cholesterol (11). ...
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The objective of this study was to evaluate the antioxidant activity of different concentrations (250, 500 and 750 ppm) of Ocimum sanctum essential oil incorporated into soybean oil. The effect of O. sanctum essential oil at 250 ppm was similar to that of BHA on inhibiting oxidation in the soybean oil, but higher concentrations of essential oil (500 and 750 ppm) showed higher protection against oxidation in comparison with that of BHA. The influence of O. sanctum essential oil on stabilizing the soybean oil was more profound at 45 °C in comparison with 60 °C. In addition, the O. sanctum essential oil was significantly effective in protecting polyunsaturated fatty acids of soybean oil during storage at both temperatures of 45 and 60 °C. Generally, the O. sanctum essential oil can be introduced as a suitable natural antioxidant that can replace synthetic antioxidants.
... Along with its religious significance, it also has substantial medicinal meaning and is used in Ayurvedic treatment. It may have a positive effect on fasting blood sugar and on blood sugar following meals [13]. The plant plays a role in the management of immunological disorders such as allergies and asthma. ...
... The juice of the leaves is used against diabetes and fever. It's anti-spasmodic properties, relieves abdominal pains and helps in lowering the blood sugar level [13,14]. ...
... Our previous study showed that a diet containing 2% OS leaf powder resulted in a significant reduction in blood glucose levels in streptozotocin-induced DM rats (14). The administration of aqueous and alcoholic extracts of OS leaves also resulted in reduced blood glucose levels in streptozotocin-induced DM rats (15,16), and prevented insulin resistance in normal rats fed with a fructose diet (17). ...
... In our previous study it was observed that supplementation with 2% dried OS leaf powder in the diet for three weeks induced anti-hyperglycemic and lipid-lowering effects in DM rats (14). The average dried OS leaf powder consumption was 4.45 g/kg/day. ...
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Ocimum sanctum L. (OS) leaves have been shown to exert diverse potential benefits in a variety of stress conditions. The present study was conducted to elucidate the effects of the fixed oil extracted from OS leaves on the blood glucose levels and serum lipid profile of streptozotocin-induced diabetic rats. In addition, the anti-oxidative activity of OS leaves to protect various organs including the liver, kidney and heart was investigated. The fixed oil of the OS leaves was extracted using hexane, and the various fatty acid contents of the oil were determined using gas chromatography-mass spectrometry. Male Wistar rats were allocated into three groups (n=7 per group): Normal control rats, diabetic rats and diabetic rats fed daily with the fixed oil for three weeks. The results showed that a-linolenic acid was the primary fatty acid contained in the fixed oil of OS. After 3 weeks of diabetic induction, the rats exhibited increased blood glucose levels and serum lipid profile, in addition to elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine kinase MB subunit (CK-MB), creatinine and blood urea nitrogen (BUN). The fixed oil significantly decreased the elevated levels of blood glucose, the serum lipid profile and the levels of serum creatinine and BUN (P<0.001), without exerting significant effects on the elevated serum levels of AST, ALT, LDH and CK-MB. Furthermore, the fixed oil increased the diabetically-reduced levels of serum insulin and decreased the rat kidney weight. Fixed oil suppressed the elevated thiobarbituric acid reactive substances (TBARS) level and increased the activity of various antioxidative enzymes in the rat renal tissue. By contrast, the fixed oil had no effect on the elevated TBARS level and the inhibited activity of the antioxidative enzymes in the rat liver and cardiac tissues. Histopathological results indicated that the fixed oil preserved the renal tissue against oxidative stress in diabetes. In summary, the results of the present study suggest that the fixed oil extracted from OS leaves exerted anti-hyperglycemic, anti-hyperlipidemic and free radical scavenging effects in diabetic rats, thus providing renal protection against diabetes. The a-linolenic acid contained in the fixed oil may be responsible for these effects.
... Regarding creatinine levels, the groups of rats fed a high-fat diet and supplemented with 5 and 10% of I. batatas leaf powder had a significantly lower creatinine level (9:73 ± 0:30 μmol/L to 11:19 ± 0:34 μmol/L) than the TN-STD (12:06 ± 0:78 μmol/L) and TP-HFD (12:70 ± 0:47 μmol/L) groups. These results show that supplementation of a diet with 10% of I. batatas leaf powder reduces the degree of liver damage and normalizes serum creatinine levels in rats fed a high-fat diet, indicating its protective effect on renal glomerular filtration capacity, as reported by Suanarunsawat and Songsak [53]. ...
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The present study consists of analyzing the phytochemical composition of Ipomoea batatas leaf powders and evaluating their antihyperlipidemic effect on rats receiving a high-fat diet. Ipomoea batatas leaves were collected from four agroecological areas of Cameroon, and powders were obtained after washing, drying, grinding, and sieving. Standard analytical methods were used to determine the phytochemical composition of two varieties (IRAD-tib1yellow-V1 and IRAD-1112white-V2) from North Z1, Adamawa Z2, West Z3, Center Z4. The effect of I. batatas leaf powder on lipid metabolism was assessed in vivo by feeding different groups of rats with a high-fat diet supplemented with 5 and 10% of I. batatas leaf powder during 30 days. At the end of the experimentation, total cholesterols, triglycerides, LDL- (low-density lipoprotein-) cholesterol, HDL- (High-density lipoprotein-) cholesterol, ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase), and creatinine were measured using commercial enzymatic kits (Spinreact, Spain). The results of phytochemical analysis of I. batatas leaf powders revealed that the total phenol content ranged from 660.173 mg GAE/100 gDW (Z1V2) to 657.76 mg GAE/100 gDW (Z3V2), the flavonoids content ranged from 282.25 mgEC/100 gDW (Z3V1) to 325.05 mgEC/100 gDW (Z4V2), and the anthraquinone content ranged from 324.05 mg/100 gDW (Z3V2) to 326.72 mg/100 gDW (Z4V2). The total antioxidant capacity ranged from 19.00 (Z1V1) to 23.48 mg AAE/gDW (Z3V2), while the IC50 ranged from 1.58 mg/mL (Z1V1) to 3.08 mg/mL (Z3V2). Rats fed a high-fat diet and supplemented with 5 and 10% of I. batatas leaf powder showed a significant (p
... These findings were supported by previous studies showed that O. basilicum has a protective effect on the kidney of rats receiving a toxic dose of mercury, lead and paracetamol (25)(26)(27). Not only that, Suanarunsawat and Songsak concluded that O. basilicum in diet induced a protective effect on renal glomerular filtration ability in diabetic rats as it reduced the elevated level of serum creatinine in the blood (28). In a more recent study, raw or gammairradiated basil added to the diet of methotrexate-treated rats markedly decreased the activities of serum liver enzymes, serum urea, creatinine and uric acid with subsequent improvement in the antioxidants level of the liver and kidney (12). ...
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Introduction: Diabetic nephropathy is the second most common secondary type of glomerular diseases among Saudi patients after systemic lupus erythematosus. Ocimum basilicum (O. basilicum) was reported to have anti-diabetic and antioxidants effects. Aim: This study aimed to evaluate the efficacy of O. basilicum in controlling STZ-induced diabetes mellitus in rats and preserving the structure of kidney against diabetes-induced nephropathy. Methods: This study utilized forty adult male Spraque-Dawley rats assigned into four groups (n=10 each); control, streptozotocin-induced diabetic, metformin-treated and O. Basilicum-treated groups. The blood glucose level (BGL), total anti-oxidant capacity (TAC), serum creatinine and BUN levels were assessed. Kidneys were dissected out and processed for histopathological and immunohistochemical assessment. Results: The BGL significantly decreased in Metformin- and O. basilicum-treated (p=0.02, p=0.01) rats while TAC significantly increased (p=0.01, p=0.003) respectively, compared to the untreated diabetic rats. In addition, O. basilicum significantly reduced (p=0.004, p=0.02) both creatinine and BUN levels compared to the untreated diabetic group, respectively. Examination of kidney of O. basilicum-treated diabetic rats revealed few degenerated renal tubules, with no inflammatory cell infiltrates, peritubular capillaries congestion and minimal peritubular collagen fibers deposition. It also reduced immunoexpression of desmin and αsmooth muscle actin in glomeruli of O. basilicum-treated diabetic rats. Conclusion: Glucose lowering and antioxidant effects of O. basilicum was evident biochemically in this study. O. basilicum could protect the kidney against diabetes-induced nephropathy as revealed biochemically and histopathologically. Further exploration of the mechanism and assessment of efficacy in human through clinical study are recommended.
... However, several adverse effects were displayed following treatment with hypolipidemic (Suanarunsawat et al., 2011, Suanarunsawat et al., 2010).Antilipidemic actions of Ocimum sanctum essential oil drugs(Bhatnagar, 1998) is also used for its hepatoprotective, cardioprotective and anti hyperlipidemic effects(Sharma et al., 2002, Prakash andGupta, 2005). Some previous study showed that supplementation with OS dried leaf powder in the diet normalized high serum lipid profile and partially protected the liver function in diabetic rats(Suanarunsawat and Songsak, 2005). Similarly, treatment with 1-2 % of OS fresh leaves in the diet for four weeks significantly decreased the serum lipid profile in normal albino rabbits(Sarkar et al., 1994). ...
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Abstract Recently, hyperlipidemia and related cardiovascular disease are becoming a major health problem in the human and even in companion animals all over the world. There are many drugs which are used as hypolipidemic commonly known such as: statins, fibrates, ezetimibe and nicotinic acid. However, most of them are expensive and have undesirable side-effects. So there is a need to search other alternative medicine that can provide better safety and efficacy with less toxic and less expensive on a long term usage. The study was conducted to investigate the prevention and cure effect of aspirin eugenol ester (AEE) on hyperlipidemia. 1. The Preventive Effect of AEE on Hyperlipidemia The experiment was conducted to evaluate the prevention effect of AEE on hyperlipidemia in SD male rats. To construct hyperlipidemia disease model, the rats were fed with high fat diet for six weeks. The drugs were administrated with the rat high fat diet at the same time to investigate the prevention effects. Intragastrical administration of the drug in each rat based on individual weekly body weight once weekly for six weeks, at the dosages of AEE 18, 36 and 54 mg/kg/day as low, medium and high dose respectively. Statin at the dosage of 10 mg/kg/day and CMC-Na at the dosage of 20 mg/kg/day was used as positive and negative control drug, respectively. Significant changes were observed on the levels of blood lipids indexes at the end of experiment. AEE at the dosage of 54 mg/kg/day for six weeks decreased TG, TC and LDL significantly (p<0.01), while statin decreased TC and LDL significantly (p<0.01), however, no effect on TG, which may suggested that AEE had prevention better effect on hyperlipidemia in SD rats than statin. AEE also showed significant change on body weight of rats during experiment which was interesting indicator for effect on obesity. 2. The Cure Effect of AEE on Hyperlipidemia To investigate the cure effect of AEE on hyperlipidemia, Wistar rats as experimental animals were fed with high fat diet to induce hyperlipidemia for eight weeks. AEE were used in three different doses, and low, medium and high dose were selected as 18, 36 and 54 mg/kg/day, respectively. To compare the effects between AEE and its component, the mole of medium dose of AEE, aspirin, and eugenol is the same, at 0.3067 moles. In the experiment, aspirin and eugenol at the molar ratio 1:1 (0.3067 mole) were set also. 0.5% of CMC-Na at the dose of 20 mg/kg was served as the vehicle control drug and the dosage of CMC-Na was close to equal in AEE and aspirin groups. Simvastatin 10 mg/kg was chosen as positive control drug to compare with AEE. The rats were divided in ten groups as blank, model groups and other eight treatment groups (n=10). Blood samples were taken for serum, which was used with conventional pharmacological methods to determine classical pathology biomarkers of hyperlipidemia, including TC, TG, LDL-C and HDL-C indexes. At the end of experiment after administrating the drug for five weeks, commercial assay kits were used and auto analyzer machine was used to measure the biomarkers of hyperlipidemia. There were significant differences in blood lipid indexes between each group. Under the present study conditions, AEE at dose 54 mg/kg/day for five weeks decreased TG, TC, LDL significantly (p<0.01) and increased HDL (p<0.05), while statin at dose 10 mg/kg and aspirin at dose 20 mg/kg decreased TG, TC, LDL significantly (p<0.01) and no increase in HDL. Eugenol at dose 18 mg/kg decreased TC and LDL significantly (p<0.01) and had no effect on TG and HDL. Integration of aspirin and eugenol at dose (20:18) mg/kg decreased TC and LDL significantly (p<0.01) and TG (p<0.05), however, no effect on HDL. Histopathological examinations for liver, stomach and intestine were performed. The results showed obviously changes on hepatic tissues among different groups. All sections from stomach and intestine showed no significant pathological changes. 3. Metabonomics of AEE Hyperlipidemia with high blood lipid levels is a major risk factor for cardiovascular disease. In the present study, hyperlipidemia disease was induced by feeding rats with HFD. A sensitive ultra-performance liquid chromatography coupled with quadrupole time-of-flight synaptic high-definition mass spectrometry (UPLC-Q-TOF/MS) method was used for the analysis of plasma. Principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were performed to investigate the metabolic changes in rats. Potential biomarkers were detected using S-plot. 22 potential biomarkers in rat plasma for hyperlipidemia were screened out. Furthermore, metabonomic pathway analysis was performed with MetPA. The results revealed that the AEE treatment against hyperlipidemia may involve in regulating the lipid metabolism, amino acid metabolism and energy metabolism. In a conclusion, AEE at the dosage 54 mg/kg/day for six weeks had preventive effect on hyperlipidemia in SD male rats more than simvastatin. There were significant differences in blood lipid indexes throughout the experiment period after administrating the drug for five weeks. The AEE optimal dose for curing hyperlipidemia in Wistar rats was considered to be 54 mg/kg/day for five weeks. The AEE against hyperlipidemia may involve in regulating the lipid metabolism, amino acid metabolism and energy metabolism. Key words: Aspirin eugenol ester (AEE), hyperlipidemia, rats, high fat diet, prevention, cure, metabonomics.
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Background: Medicinal plants constitute an important source of potential therapeutic agents for diabetes. Objective: In the study, we aimed to investigate the pre-treatment effect or preventive effects of Moringa oleifera (MO) leaves on blood sugar of rats. Materials and method: This experimental study was carried out in the department of Pharmacology and Therapeutics of Sir Salimullah Medical College in collaboration with Bangladesh Council of Scientific and Industrial Research (BCSIR), Dhaka. A total 24 long Evans rats were included in this study and divided in to four groups. Hyperglycemia was induced on rats using alloxan (100 mg/kg body weight, intraperitioneally). Blood sample was collected from tail vein by tail tipping method. Pre-treatment effect or preventive role of Moringa oleifera (drumstick) leaf powder on diabetogenesis produced by Alloxan in rats was tested by giving 50 mg/rat/day Moringa oleifera leaf powder for 14 days orally as pre-treatment along with standard rat feed. Then alloxan was administered intraperitoneally on 15th day of the experiment and 50mg/rat/day Moringa oleifera leaf powder was given for 7 days as post-treatment. Results: No significant effect of MO on blood glucose level was observed on normal rats and non significant hypoglycaemic effect was found in rats that were pretreated with MO. Conclusion: The present study suggests that Moringa oleifera leaf powder did not produce any significant protective effect in diabetogenesis produced by alloxan though it has hypoglycaemic effect.
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Hyperglycemia is considered a primary cause of diabetic vascular complications and is associated with oxidative stress, impaired trace element and lipid metabolism as well as pancreatic enzyme abnormalities. The role of trace elements in some of the metabolic dysfunctions and their contributions in the development of vascular complications is not clear. Therefore, the present study investigates the relationship among diabetes mellitus, trace elements status, advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipid profiles, antioxidant status, nitric oxide and pancreatic amylase activity in the sera of 55 non-insulin-dependent diabetes mellitus (NIDDM; 35 with microvascular complications and 20 without vascular complications), 40 insulin-dependent diabetes mellitus (IDDM; 25 with microvascular and 15 without microvascular complications), and 20 nondiabetic healthy control subjects. The mean age of the diabetic patients was similar to that of control. The mean duration of the disease was 11.8 +/- 6.8 years (3-27 years) in IDDM and 7.1 +/- 4.7 years (1-15 years) in NIDDM. Plasma Cu, Zn, Mg, Ca, thiobarbituric acid-reactive substance (i.e. malondialdehyde; MDA), nitric oxide (NO), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), ceruloplasmin (Cp) and amylase activities as well as AOPP were assessed spectrophotometrically whereas AGEs were estimated spectrofluorometrically in two types of diabetes mellitus (DM) as well as control subjects of matched sex and ages. SOD, CAT and Cp activities were decreased whereas serum alpha-amylase activity was increased in two types of DM in comparison to the corresponding activities of the control subjects. The plasma levels of MDA, NO and Cu were increased but GSH, Zn, Mg and Ca levels were significantly diminished in diabetic patients as compared to the controls. The averages of total cholesterol (CHOL), triglyceride (TG) and low-density lipoprotein-cholesterol (LDLc) were higher in both types of diabetes mellitus in comparison to the control subjects. The mean value of high-density lipoprotein-cholesterol (HDLc) was lower in both types of diabetes mellitus. Further, the mean values of AGEs and AOPP were elevated in diabetic patients vs. control. These parameters are significantly higher in NIDDM patients when compared to the IDDM subjects. Slight but not significant differences in these parameters were observed in patients with diabetic complications when compared to that of without diabetic complications. These findings may explain the role of impaired trace element status, defect of antioxidants and increased of AGE and AOPP in the pathogenesis of pancreas and the vascular complications of diabetes mellitus. Oxidative stress is increased in both types of DM, but it is more in NIDDM patients than in IDDM subjects. In addition, oxidative stress also plays an important role in the formation of AGEs and AOPP in DM.