antidyslipidemic effect of ocimum sanctum leaf extract in streptozotocin induced diabetic rats

6
ORIGINAL ARTICLE Antidyslipidemic Effect of Ocimum sanctum Leaf Extract in Streptozotocin Induced Diabetic Rats Ishrat Husain Ramesh Chander Jitendra Kumar Saxena Abbas Ali Mahdi Farzana Mahdi Received: 28 June 2013 / Accepted: 11 November 2013 Ó 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 Á Anti-dyslipidemic agent Á Natural antioxidants Á Postheparin lipolytic activity Á Streptozotocin induced-diabetes Á 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 Á R. Chander Á F. Mahdi (&) Department of Biochemistry, Era’s Lucknow Medical College & Hospital, Sarfarazganj, Hardoi Road, Lucknow 226003, India e-mail: [email protected]; [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

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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];

[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.

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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.

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