antidyslipidemic effect of ocimum sanctum leaf extract in streptozotocin induced diabetic rats
TRANSCRIPT
ORIGINAL ARTICLE
Antidyslipidemic Effect of Ocimum sanctum Leaf Extractin Streptozotocin Induced Diabetic Rats
Ishrat Husain • Ramesh Chander •
Jitendra Kumar Saxena • Abbas Ali Mahdi •
Farzana Mahdi
Received: 28 June 2013 / Accepted: 11 November 2013
� Association of Clinical Biochemists of India 2014
Abstract The antidyslipidemic activity of Ocimum sanc-
tum leaf extract was studied in streptozotocin induced diabetic
rats. In this model, there was significant increase in plasma
markers of diabetic-dyslipidemia following diminution of
lipid metabolizing enzymes. Oral administration of leaf
extract (500 mg/kg b.w.p.o.) for 15 days resulted in signifi-
cant decrease in diabetogenic and dyslipidemia parameters;
namely blood glucose, glycosylated hemoglobin, lipid per-
oxide, free fatty acids, small dense low density lipoprotein,
lipid and protein components of plasma lipoproteins, adipose
and liver. The regulation of lipids was accompanied by
stimulation of postheparin lipolytic activity, reactivation of
lecithin cholesterol acyl transferase and hepatic lipoprotein
lipase enzymes. The results of the present study demonstrated
antidyslipidemic and antioxidant activities in leaf extract of
O. sanctum which could be used in prevention of diabetic-
dyslipidemia and related complications.
Keywords Ocimum sanctum � Anti-dyslipidemic agent �Natural antioxidants � Postheparin lipolytic activity �Streptozotocin induced-diabetes �Hypoglycemic agent
Introduction
Ocimum sanctum, known as Tulsi in Hindi and Holy Basil in
English, is an aromatic-medicinal plant of the genus Oci-
mum belonging to family Lamiaceae. The plant is native
throughout the old world tropics, distributed and cultivated
throughout India. Tulsi, well known for its therapeutic
potential, has made an important contribution to the field of
science from ancient times as also to modern research due to
its large number of medicinal properties [1]. It has a variety
of biological/pharmacological activities such as antibacte-
rial, antiviral, antifungal, antiprotozoal, antimalarial, ant-
helmentic, antidiarrhoeal, analgesic, antipyretic, anti-
inflammatory, antiallergic, antihypertensive, cardio protec-
tive, central nervous system depressant, memory enhancer,
anti hypercholesterolemic, hepatoprotective, antidiabetic,
antiasthmatic, antithyroidic, anti oxidant, anticancer, chemo
preventive, radio protective, immunomodulatory, antifertil-
ity, antiulcer, antiarthritic, adaptogenic/antistress, anticata-
ract, antileucodermal and anti-coagulant activities [2, 3]. The
essential and fixed oils from Ocimum sanctum, containing
eugenol and ursolic acid as major constituent, found to
possess antidiabetic, cardio protective, vasorelaxant, hypo-
lipidemic and hepatoprotective activities [4].
It is well established that patients having diabetic–
dyslipidemia; the disorders of lipid and lipoprotein
metabolism associated with diabetes mellitus, are at
increased risk of so many vascular complications including
cardiovascular diseases (CVD), Cerebrovescular diseases,
atherosclerosis, coronary heart disease [5]. These second-
ary complications in diabetic patients accounts for more
than 70 % of all deaths in individuals with diabetes [6].
The centers for diabetes control and prevention reported
that 70–97 % of individuals with diabetes have dyslipide-
mia. Moreover, it is documented that diabetic-dyslipidemia
I. Husain � R. Chander � F. Mahdi (&)
Department of Biochemistry, Era’s Lucknow Medical College &
Hospital, Sarfarazganj, Hardoi Road, Lucknow 226003, India
e-mail: [email protected]; [email protected];
J. K. Saxena
Division of Biochemistry, Central Drug Research Institute,
Lucknow, India
A. A. Mahdi
Department of Biochemistry, King George’s Medical University,
Lucknow, India
123
Ind J Clin Biochem
DOI 10.1007/s12291-013-0404-2
is also associated with increased oxidative stress and dis-
playing impaired normal biological functions and impor-
tant activities in patients. Therefore, to decrease vascular
complications in patients with diabetes, equal effort must
be applied to controlling lipid level and oxidative stress as
well as blood glucose [7]. The current therapies used for
controlling dyslipidemia; fibrates, statins and bile acid se-
questraints or antidiabetic drugs; thiazolidinediones, and
biguanides are almost inefficient to regulate lipid metabo-
lism. Furthermore, these drugs also cause a number of
serious adverse effects in patients. On the other hand since
natural products are considered free from side effects, safe
and cost effective, being preferred for R&D of potential
drugs [8, 9]. This study was, therefore, planned to explore
antidyslipidemic activity of Ocimum sanctum leaf extract
in streptozotocin induced diabetic—dyslipidemia in rats.
Materials and Methods
Preparation of Leaf Extract
Ocimum sanctum leaves were collected from local area of
Lucknow and identified taxonomically by the Department of
Pharmacology, Era’s Lucknow Medical College and Hos-
pital, Lucknow. A voucher specimen was also submitted. O.
sanctum leaves were dried under shade and made into fine
powder using laboratory mill. Powder (250 g) was extracted
thrice with 500 ml portions of 95 % ethyl alcohol in a per-
colator at room temperature. Time allowed for each extrac-
tion was 4 h. The leaf extract obtained after third extraction
was colorless. All the extracts were mixed (1400 ml).Alco-
hol was distilled out at reduced temperature (20 �C) and
pressure (100 psi) in a rotatory evaporator. This whole mass
was taken out in a pre-weight beaker and subjected to vac-
uum drying for 6 h. Finally this yielded 16.25 g (6.5 %w/w)
of crude extract which was used for in vivo studies. Strer-
ptozotocin (STZ) and standard drug glibenclamide were
procured from Sigma Chemical Company; St. Louis, MO,
USA. All other chemicals used, were of high purity and
analytical grade. Both test drugs were macerated with 1 %
(w/v) aqueous gum acacia and a homogeneous suspension of
O sanctum leaf extract (50 mg/ml) and glibenclamide
(0.6 mg/10 ml) were prepared. These suspensions were fed
orally, once daily in experimental rats. The rats in control
group were fed with same amount of aqueous gum acacia.
The suspensions were prepared fresh daily.
Antidyslipidemic Activity in Streptozotocin Induced
Diabetic Rats
Animal study was performed with the approval of Animal
Care Committee of Era’s Lucknow Medical College and
Hospital, Lucknow, India and confirmed to the guide lines for
the Care and Use of Laboratory Animals of the Institute. Male
adult rats of Wistar strain (200–240 g) bred in the animal
house of the Institute were used. A group of six animals in a
cage were kept in controlled conditions, temperature
25–26 �C, relative humidity 50–60 % and 12/12 h light/dark
cycle (light from 08:00 AM–08:00 PM) and provided with
standard pellet diet(Dayal Industries, Barabanki, UP, India)
and water adlibitum. Diabetes was induced by intraperitoneal
injection of streptozotocin (65 mg/kg b.w) in animals
[10].After 3 days of injection, diabetes was confirmed by
glucometer. Rats with blood glucose level 300–350 mg/dl
were included in the study. Rest of the rats whose blood
glucose level was below 300 mg/dl, were rejected. The nor-
mal non-diabetic rats were used to serve as control.
Experimental Design
The rats were divided in four groups having six animals in
each as follows: Group 1, control rats (on 2 % aqueous gum
acacia); Group 2, STZ treated diabetic rats (on 2 % aqueous
gum acacia); Group 3, STZ treated diabetic rats ? O.
sanctum (500 mg/kg b.w); Group 4, STZ treated diabetic
rats ? glibenclamide (600 lg/kg b.w.). After 15 days of
feeding, rats were fasted overnight, anaesthetized with
thiopental solution, and injected (ip) with 0.1 ml/kg b.w. of
10 mg/ml solution of heparin. After 15 min blood was
withdrawn from retro-orbital plexus and collected in EDTA
coated tubes. Thereafter rats were sacrificed; their liver and
adipose tissue (Abdominal fat pads) were excised.
Biochemical Analysis of Blood and Plasma
Lipoproteins
The blood was centrifuged and plasma was separated. The
glycosylated hemoglobin (HbA1C) in RBC and plasma levels
of small dense low density lipoprotein (sd-LDL) were
assayed by standard spectrophotometric methods [11, 12].
Plasma was also used for the assay of lecithin cholesterol
acyl transferase activity (LCAT), postheparin lipolytic
activity (PHLA), glucose, free fatty acid (FFA), lipid per-
oxide (LPO)by the methods reported earlier [13]. A portion
of plasma was fractionated into very low density lipoprotein
(VLDL), low density lipoprotein (LDL) and high density
lipoprotein (HDL) by polyanionic precipitation methods
[14]. Plasma as well as lipoproteins were measured for their
total cholesterol (TC), phospholipids (PL), triglyceride (TG)
and protein by standard procedures reported earlier [15].
Biochemical Analysis of Adipose Tissue and Liver
Adipose tissue and liver were homogenized (10 % w/v) in
cold 100 mM phosphate buffer pH 7.2 and used for the
Ind J Clin Biochem
123
assay of lipoprotein lipase activity (LPL) as well as TC, PL
and TG content in them [15].
Statistical Analysis
One way analysis of variance (ANOVA-New man’s student
t test) was performed by comparison of values for STZ
treated group with control, STZ and drug treated group with
STZ. All hypothesis testing were two-tailed. p \ 0.05 was
considered statistically significant and the results were
expressed as mean ± SD. The statistical analysis was car-
ried out by the Graph Pad INSTAT 3.0 software.
Results
Effect of O. sanctum in Streptozotocin Induced
Diabetic Dyslipidemia
The challenge with streptozotocin (65 mg/kg; ip) caused a
significant increase in diabetogenic and dyslipidemia
parameters; namely blood levels of glucose by 270 %;
HbA1C, 57 %; LPO, 40 % and free fatty acids, 77 % in rats.
Although sd-LDL was not present in control rats, however, it
was shown to appear (4.83 mg/dl) in diabetic rats. Treatment
with O. sanctum leaf extract and glibenclamide caused
reversal in the levels of blood glucose by 32 and 50 %,
HbA1C by 18 and 21 %, LPO by 23 and 20 %, FFA by 35 and
36 % following decrease in the levels of sd-LDL by 38 and
15 % respectively (Table 1). The data in Table 2 show that
induction of diabetes in rats caused increase in their serum
levels of TC, PL, TG and protein by 58, 41,102 and 24 %
respectively. Treatment with O. sanctum caused reversal in
increased levels of TC, PL, TG and protein by 29, 30, 36 and
14 % respectively. The analysis of lipid and apoprotein
components of b-lipoproteins showed that administration of
STZ in rats caused significant increase in TC, PL, TG and
apoprotein components of VLDL by 72, 47, 82 and 33 % as
well as of LDL by 39, 55, 29 and 35 % respectively.
Treatment with O. sanctum afforded reversal in the levels of
VLDL-TC, PL, TG and apoprotein by 33, 30, 42 and 20 % as
well as LDL-TC, PL, TG and apoprotein by 21, 23, 18 and
18 % respectively. The lowering effect of O. sanctum for
PL, TG and protein components of these lipoproteins was
comparable to that of glibenclamide, however, cholesterol
lowering effect of test-extract was more than the standard
drug. Furthermore, induction of diabetes adversely affects to
HDL as it caused decrease in levels of lipids and apoprotein
components of this lipoprotein by 20–25 %.Treatment with
O. sanctum partially recovered the levels of HDL–TC, PL,
TG, and apo-HDL by 15, 19, 17 and 18 % respectively. The
recovery of lipid and apoprotein components of HDL by
feeding with glibenclamide was poor and non significant.
Ta
ble
1E
ffec
to
fO
.sa
nct
um
on
pla
sma
bio
chem
ical
par
amet
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stre
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cin
ind
uce
dd
iab
etic
-dy
slip
idem
iain
rats
Gro
up
sB
loo
dg
luco
se(m
g/d
l)G
lyco
syla
ted
hae
mo
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bin
(g%
)
Lip
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e
(lm
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MD
A/d
l)
Sm
all
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se-L
DL
cho
lest
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l
(mg
/dl)
Fre
efa
tty
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(lm
ole
/l)
Co
ntr
ol
85
.77
±1
2.5
31
.87
±0
.16
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2±
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23
0±
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Dia
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17
.47
**
*±
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.94
**
±0
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7)
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*±
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(?4
0)
4.8
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**
±1
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40
8*
**
±5
8(?
77
)
Dia
bet
ic?
O.
san
ctu
m(5
00
mg
/
Kg
b.w
.)
18
2.3
3*
*±
20
.31
(-3
2)
2.4
2*
±0
.22
(-1
8)
2.4
0*
*0
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(-2
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03
**
±0
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(-3
8)
26
4*
*±
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(-3
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(60
0l
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.)
15
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**
±1
7.6
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50
)2
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**
±0
.19
(-2
1)
2.4
9*
*±
0.2
4(-
20
)4
.09
3*
±1
.99
(-1
5)
26
3*
*±
41
(-3
6)
Val
ues
are
mea
n±
SD
of
six
rats
.V
alu
esin
the
par
enth
esis
are
%ch
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01
Ind J Clin Biochem
123
Effect of O. sanctum in Streptozotocin Induced Lipid
Changes in Adipose, Liver and Plasma of Diabetic Rats
The data in Table 3 show that induction of diabetes in rats
caused stimulation in LPL activity (79 %) following
depletion of TC (31 %), PL (26 %) and TG (48 %) in
adipose tissue, however these parameters were partially
reversed by 30, 14, 17 and 36 %, respectively, after treat-
ment with O sanctum. On the other hand, in case of liver,
the situation was just opposite, where diabetes caused
diminution of LPL activity (45 %), which was accompa-
nied with marked accumulation of TC, PL, TG by 67, 52
and 93 % respectively. Treatment with O. sanctum caused
reversal in altered levels of hepatic LPL activity, TC, PL
and TG by 54, 33, 23 and 34 % respectively. The challenge
with streptozotocin also caused the inhibition of PHLA
(41 %) and plasma LCAT activity (34 %) which was found
reactivated by 27 and 29 %, respectively, in O. sanctum
treated diabetic rats. The Antidyslipidemic effect of O.
sanctum treatment, on adipose tissue was comparable to
that of glibenclamide. However, lowering caused by O.
sanctum in the level of hepatic lipids, reactivation of LPL
as well as plasma PHLA and LCAT was comparatively
more than that of glibenclamide.
Discussion
In the present study, O. sanctum leaf extract was tested for
its antidyslipidemic activity in STZ induced diabetes in
rats. Challenge with STZ begin an autoimmune process
that results in the destruction of langerhans islets b-cells
with emergence of clinical diabetes within 2–4 days, and
that is why this animal model have been used for primary
screening of test drugs for antidiabetic activity [10]. We
found that intoxication with STZ caused a significant
increase in diabetogenic and dyslipidemia parameters;
namely blood glucose, HbA1C, LPO, FFA and sd-LDL
lipid and protein components of plasma lipoproteins, as
well as adipose and liver. The abnormality with lipid
metabolism was accompanied with diminution of PHLA,
LCAT and hepatic LPL activities in rats. Treatment with O.
sanctum and glibenclamide for 15 days caused reversal,
but with varying extents, in the levels of these biochemical
parameters of diabetic–dyslipidemia.
In diabetes mellitus, decreased bioavailability of insulin
suppresses the utilization of glucose in skeletal muscles
and other peripheral tissues thus produces hyperglycemia
which causes a variety of pathologic changes through the
formation and accumulation of advanced glycation end
Table 2 Effect of O. sanctum on lipid and apoprotein levels of plasma lipoproteins in streptozotocin induced diabetic dyslipidemia in rats
Groups/parameters Control Diabetic Diabetic ? O. sanctum
(500 mg/Kg b.w.)
Diabetic ? glibenclamide
(600 lg/Kg b.w.)
Serum
TC (mg/dl) 78.87 ± 5.90 124.55*** ± 15.96 (?58) 89.01** ± 11.79 (-29) 104.21* ± 13.35 (-16)
PL (mg/dl) 74.13 ± 6.50 104.48*** ± 9.18 (?41) 73.25** ± 7.15 (-30) 75.24** ± 6.16 (-28)
TG (mg/dl) 83.06 ± 9.55 168.08** ± 15.15 (?102) 107.28*** ± 11.63 (-36) 117.61** ± 11.07 (-30)
Protein (g/dl) 6.88 ± 0.80 8.51** ± 1.00 (?24) 7.30* ± 0.50 (-14) 7.01* ± 0.61 (-18)
VLDL
TC (mg/dl) 7.73 ± 0.92 13.26*** ± 1.32 (?72) 8.88** ± 1.32 (-33) 10.71* ± 2.13 (-19)
PL (mg/dl) 13.55 ± 1.04 19.96** ± 1.54 (?47) 13.95** ± 0.96 (-30) 16.08* ± 2.13 (-19)
TG (mg/dl) 37.36 ± 3.92 67.97*** ± 7.19 (?82) 39.38*** ± 4.21 (-42) 40.84** ± 3.49 (-40)
Apo protein (mg/dl) 6.37 ± 0.61 8.46*** ± 1.52 (?33) 6.77* ± 1.20 (-20) 6.54** ± 0.60 (-23)
LDL
TC (mg/dl) 16.25 ± 2.22 22.63** ± 2.82 (?39) 17.87* ± 1.17 (-21) 17.66* ± 1.94 (-22)
PL (mg/dl) 10.16 ± 1.63 15.75*** ± 1.78 (?55) 12.20* ± 1.07 (-23) 11.30** ± 1.31 (-28)
TG (mg/dl) 20.45 ± 2.13 26.36** ± 3.76 (?29) 21.67* ± 3.19 (-18) 21.10** ± 3.18 (-18)
Apo Protein (mg/dl) 13.08 ± 1.75 17.67*** ± 1.65 (?35) 14.45* ± 1.34 (-18) 14.64* ± 1.25 (-17)
HDL
TC (mg/dl) 44.33 ± 5.68 35.25** ± 3.71 (-20) 40.51** ± 4.37 (?15) 37.75NS ± 3.21 (?7)
PL (mg/dl) 40.17 ± 7.01 31.75** ± 2.70 (-21) 37.80** ± 3.96 (?19) 33.75NS ± 3.26 (?6)
TG (mg/dl) 16.43 ± 1.40 12.36** ± 1.53 (-25) 14.43* ± 1.43 (?17) 13.62NS ± 1.55 (?10)
Apo Protein (mg/dl) 169.14 ± 24.53 129.79** ± 15.85 (-23) 152.57** ± 19.67 (?18) 143.51NS ± 26.07 (?11)
Values are mean ± SD of six rats. Values in the parenthesis are % change. STZ treated diabetic group is compared with normal rats and
STZ ? drug treated groups with diabetic group
* p \ 0.05; * p \ 0.01, *** p \ 0.001
Ind J Clin Biochem
123
products, increased oxidative stress, activation of protein
kinase C pathway, increased activity of hexosamine path-
way, vascular inflammation and impairment of insulin
action in vascular tissues [16]. Insulin effects on liver
apoprotein production and VLDL secretion, regulation of
LPL, actions of cholesteryl ester transfer protein (CETP)
and lipolysis of fat in adipose tissue and glucose metabo-
lism in muscles. All these complications are likely to be
responsible for diabetic–dyslipidemia. Decreased bio-
availability of insulin or its resistance to adipocytes, pro-
vokes lipolysis of fat depots through activation of hormone
sensitive lipase which causes an increase in FFA flux, is
very likely the initial step in development of dyslipidemia.
The ensuing increase in fatty acid transport to the liver has
been shown to stimulate secretion of VLDL. Simulta-
neously, hyperglycemia induced activation of protein
kinase C increases expression of transforming growth
factor–b which suppresses the synthesis of glucosamino-
glycans in capillary endothelium surface that lead to defect
in LPL binding and consequent poor clearance of VLDL in
diabetics [17]. The involvement of hyperglycemia may
affect the synthesis, also cause structural modifications
such as glycosylation and oxidative degradation as well as
functional changes in proteins and lipids at any situation.
This is also true for CETP and LCAT which are reported to
be responsible for abnormalities with HDL metabolism and
appearance of sd-LDL in diabetics [18]. Furthermore,
structural modifications in lipoproteins made them a
defective substrate for their catabolism through LPL and
hepatic LDL receptors. Thus characteristic diabetic-dysli-
pidemia is that of low HDL–cholesterol, hypertriglycer-
idemia-predominantly in VLDL and presence of high
atherogenic sd-LDL particles.
Earlier studies have shown that feeding with O. sanctum
leaf extract caused lowering in blood sugar levels, serum
and tissue lipids in diabetic rats [19]. It regulate carbohy-
drate metabolism in STZ induced diabetes in rats [20]. The
glucose lowering effects of O. sanctum leaf was found to
be mediated through its insulin secretagogues effects on
pancreas [21]. The phytochemical studies showed that O.
sanctum contains a variety of medicinal-chemical com-
pounds. Some of the main constituents of leaf of O.
sanctum are phenolic compounds, flavonoids, sesquiter-
penes and monoterpenes, glycosides, Steroids, sterols as
well as volatile and non volatile, (Fixed) oils [2, 3]. It is
suggested that all or some of these bioactive compounds
may be responsible for hypoglycemic, antidyslipidemic
and antioxidant effects of the medicinal plants [22, 23].
Kelm et al. [24, 25] found that leaves and stems of Ocimum
sanctum contains cirsilineol, cirsimaritin, isothymusin,
isothymonin, apigenin, rosmarinic acid, and appreciable
quantities of eugenol and all these are known to possess
potent lipid lowering and antioxidant activities. Suanar-
unsawat et al. [26] also reported that feeding with essential
Table 3 Effect of O. sanctum and on adipose and liver lipids and plasma enzymes in streptozotocin induced diabetic-dyslipidemia in rats
Groups/parameters Control Diabetic Diabetic ? O. sanctum
(500 mg/Kg b.w.)
Diabetic ? glibenclamide
(600 lg/Kg b.w.)
Adipose tissue
TC (mg/dl) 4.50 ± 0.54 3.10** ± 0.35 (-31) 3.53* ± 0.61 (?14) 3.58* ± 0.40 (?15)
PL (mg/dl) 8.10 ± 0.73 5.99** ± 0.55 (-26) 7.05* ± 0.65 (?17) 7.31* ± 0.59 (?12)
TG (mg/dl) 451.26 ± 44.73 234.92*** ± 23.43 (-48) 319.73*** ± 31.33 (?36) 347.00*** ± 32.15 (?48)
LPL Activity (nmol free fatty acid
formed/h/mg protein)
85.09 ± 6.98 152.59*** ± 14.37 (?79) 106.85** ± 12.75 (-30) 98.42*** ± 13.40 (-35)
Liver
TC (mg/dl) 5.09 ± 0.56 8.54*** ± 0.88 (?67) 5.68*** ± 0.73 (-33) 6.55** ± 0.58 (-23)
PL (mg/dl) 16.54 ± 1.34 25.10*** ± 2.79 (?52) 19.39** ± 1.88 (-23) 21.42* ± 2.21 (-15)
TG (mg/dl) 10.05 ± 0.87 19.41*** ± 1.75 (?93) 12.70 *** ± 1.42 (-34) 15.17** ± 1.44 (-23)
LPL Activity (nmol free fatty acid
formed/h/mg protein)
145.26 ± 13.57 80.60*** ± 10.58 (-45) 124.40*** ± 12.57 (? 54) 100.19** ± 9.37 (?24)
Plasma
PHLA (nmol cholesterol released/h/
L plasma)
68.69 ± 5.54 40.39*** ± 8.8 51.25** ± 6.30 47.21* ± 6.73 (?17)
1 (-41) (?27)
LCAT (nmol free fatty acid formed/
mL plasma)
22.97 ± 3.16 15.26*** ± 1.47 (-34) 19.61** ± 1.05 (?29) 17.60* ± 1.41 (?15)
Values are mean ± SD of six rats. Values in the parenthesis are % change. STZ treated diabetic group is compared with normal rats and
STZ ? drug treated groups with diabetic group
* p \ 0.05; ** p \ 0.01, *** p \ 0.001
Ind J Clin Biochem
123
oil extracted from O. sanctum leaf exerted antidiabetic,
antidyslipidemic and antioxidant activity in cholesterol
fed—hyperlipidemic and STZ-induced diabetic rats.
The present work is a detail report on the mechanism of
action of O. sanctum leaf to act as an antidyslipidemic
agent in STZ induced diabetes in rats. Besides its antidia-
betic, antiglycation and antilipoperoxidative effects, the
lipid lowering action of O. sanctum may be due to reacti-
vation of, PHLA, LCAT and tissue LPL enzymes. Treat-
ment caused beneficial effect on HDL synthesis that may
also contributed to regulate lipid metabolism and to reduce
the formation of atherogenic sd-LDL in diabetic rats. The
study revealed that O. sanctum is a better drug as a natural
product to regress dyslipidemia and oxidative stress in
diabetes. Further work to assess the antidyslipidemic
activity of different fractions of O. sanctum leaf in STZ
induced diabetic rats is under progress to substantiate the
present findings.
Acknowledgments The author is thankful to Indian Council of
Medical Research, New Delhi for financial support vide project
sanction No. 45/37/2009/BMS/TRM, dated 22/12/2009.
References
1. NIIR Board. Ocimum sanctum. In: National Institute of Industrial
Research (NIIR Board) India, editor. Compendium of Medicinal
Plants. India: NIIR; 2004. p. 320. doi:978-81-86623-80-0.
2. Singh U, Singh S, Kochhar A. Therapeutic potential of antidia-
betic nutraceuticals. Phytopharmacology. 2012;2(1):144–69.
3. Pandey G, Madhuri S. Pharmacological activities of Ocimum
sanctum (tulsi): a review. Inter J Pharmac Sci Rev Res.
2010;5:61–6.
4. Singh S, Taneja M, Majumdar DK. Biological activities of Oci-
mum sanctum L. fixed oil: an overview. Indian J Exp Biol.
2007;45:403–12.
5. Mohammed K, Ali KM, Narayan V, Tandon N. Diabetes and
coronary heart disease: current perspectives. Indian J Med Res.
2010;132:584–97.
6. Kershnar AK, Daniels SR, Imperatore G, Palla SL, Petitti DB,
Pettitt DJ, Marcovina S, Dolan LM, Hamman RF, Liese AD,
Daniels SR, Imperatore G, Palla SL, Petitti DB, Pettitt DJ,
Marcovina S, Dolan LM, Hamman RF, Liese AD, Pihoker C,
Rodriguez BL. Lipid abnormalities are prevalent in youth with
type 1 and type 2 diabetes: the SEARCH for diabetes in youth
study. J Pediatr. 2006;149:314–9.
7. American Diabetes Association. Management of dyslipidemia in
adults with diabetes (position statement). Diabetes Care.
2003;26:S83–6.
8. Singh RK, Sharma B. Certain traditional Indian plants and their
therapeutic applications: a review. VRI Phytomed. 2013;1(1):1–11.
9. Jaiswal D, Rai PK, Mehta S, Chatterji S, Shukla S, Rai DK,
Sharma G, Sharma B, Watal G. Role of drumstick leaves (Mo-
ringa oleifera) in regulation of diabetes-induced oxidative stress
Asian Pacific. J Tropical Med. 2013;6:426–32.
10. Akbarzadeh A, Norouzian D, Mehrabi MR, Jamshidi Sh, Farh-
angi A, Allah Verdi A, Mofidian SMA, Lame RB. Induction of
diabetes by streptozotocin in rats. Indian J Clin Biochem.
2007;22(2):60–4.
11. Goldstein DE, Parker KM, England JD, Wiedmeyer HM, Raw-
lings SS, Randall H, Randier L, Simonds JF, Russell P. Clinical
application of glycosylated hemoglobin measurement. Diabetes.
1982;31(Suppl 3):70–8.
12. Hirano T, Ito Y, Saegusa H, Yoshino G. A novel and simple
method for quantification of small dense LDL. J Lipid Res.
2003;44:2193–201.
13. Kumar V, Singh P, Chander R, Mahdi F, Singh S, Singh R,
Khanna AK, Saxena JK, Mahdi AA, Singh VK. Hypolipidemic
activity of Hibiscus rosa-sinensis root in rats. Indian J Biochem
Biophys. 2009;46(6):507–10.
14. Burnstein M, Legmann P. Lipoprotein precipitation. In: Clarkson
TB, editor. Monographs on atherosclerosis, vol. II. London: S.
Kargar; 1982. p. 76–83.
15. Kumar V, Mahdi F, Chander R, Singh R, Mahdi AA, Khanna AK,
Bhatt S, Kushwaha RS, Jawad K, Saxena JK, Singh RK. Hypolipi-
demic and antioxidant activity of Anthocephalus indicus (Kadam)
root extract. Indian J Biochem Biophys. 2010;47(2):104–9.
16. Park Y, Wu J, Zhang H, Wang Y, Zhang C. Vascular dysfunction
in Type 2 diabetes: emerging targets for therapy. Expert Rev
Cardiovasc Ther. 2009;7(3):209–13.
17. Das S. Current understanding of risk factors and mechanisms in
the pathogenesis of macrovascular disease in diabetes mellitus.
Indian Acad Clin Med. 2001;2(3):214–21.
18. Goldberg IJ. Clinical Review 124; diabetic dyslipidemia :causes
and consequences. J Clin Endocrinol Metabol. 2001;86:965–71.
19. Suanarunsawat T, Ayutthaya WDN, Songsak T, Thirawarapan S,
Poungshompoo S. Lipid-lowering and antioxidative activities of
aqueous extracts of Ocimum sanctum L. leaves in rats fed with a
high-cholesterol diet. Oxid Med Cell Longev. 2011;. doi:10.1155/
2011/962025.
20. Vats V, Yadav SP, Grover JK. Ethanolic extract of Ocimum
sanctum leaves partially attenuates streptozotocin-induced alter-
ations in glycogen content and carbohydrate metabolism in rats.
J Ethnopharmacol. 2004;90:155–60.
21. Hannan JM, Marenah L, Ali L, Rokeya B, Flatt PR, Abdel Wahab
YH. Ocimum sanctum leaf extracts stimulate insulin secretion
from perfused pancreas, isolated islets and clonal pancreatic beta-
cells. J Endocrinol. 2006;189(1):127–36.
22. Mehta S, Rai PK, Rai DK, Rai NK, Rai AK, Bicanic D, Sharma
B, Watal G. LIBS-based detection of antioxidant elements in
seeds of Emblica officinalis. Food Biophys. 2010;5(3):186–92.
23. Sharma RK, Chatterji S, Rai DK, Mehta S, Rai PK, Singh RK,
Watal G, Sharma B. Antioxidant activities and phenolic contents
of the aqueous extracts of some Indian medicinal plants. J Med
Plants Res. 2009;3(11):944–8.
24. Kelm MA, Nair MG, Strasburg GM, DeWitt DL. Antioxidant and
cyclooxygenase inhibitory phenolic compounds from Ocimum
sanctum Linn. Phytomedicine. 2000;7(1):7–13.
25. Pandey G. An overview on certain anticancer natural products.
J Pharm Res. 2009;2(12):1799–1803. ISSN-0974-6943. http://
www.cabdirect.org/abstracts/20103127047.html;jsessionid=
5F7778EADAE7E0B28D0D470953E41206.
26. Suanarunsawat T, Ayutthaya WDN, Songsak T, Thirawarapan S,
Poungshompoo S. Antioxidant and lipid lowering effects of
essential oils extracted from Ocimum sanctum leaves in rats fed
with a high cholesterol diet. J Clin Biochem Nutr. 2010;46:52–9.
Ind J Clin Biochem
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