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Indian Journal of Experimental Biology

Vol. 51, September 2013, pp. 702-708

Anti-diabetic and antihyperlipidemic effect of allopolyherbal formulation in


OGTT and STZ-induced diabetic rat model
Swati Manik, Vinod Gauttam & A N Kalia*
Department of Pharmacognosy, ISF College of Pharmacy, Moga, 1420 01, India
Received 11 October 2012; revised 3 June 2013
The present study was undertaken to evaluate the antidiabetic and antihyperlipidemic activities of Allopolyherbal
formulation (APHF) consisting of combinations of three well known medicinal plants used in traditional medicines (Trigonella
foenum graceum, Momordica charantia, Aegle marmelos) and synthetic oral hypoglycaemic drug (Glipizide-GL). The
optimized combination of lyophilized hydro-alcoholic extracts of drugs was 2:2:1 using OGTT model. The optimized PHF was
simultaneously administered with GL and optimized using OGTT model in diabetic rats and further studied in STZ-induced
diabetic rats for 21 days. The results (serum glucose level, lipid profile, hepatic enzymes and body weight) were compared with
the standard drug GL (10 mg/kg body wt). The optimized APHF (500+5 mg/kg body wt) has shown significant
antihyperglycemic and antihyperlipidemic activities. The results were comparable with the standard; even better than the GL
(10 mg/kg body wt) alone. The proposed hypothesis has reduced the no. of drug components from eight to three and dose
almost 50 % of both PHF and GL which fulfil the FDA requirements for export. Thus the developed APHF will be an ideal
alternative for the existing hypoglycemic formulations in the market with an additional advantage of hypolipidemic effect and
minimizing the cardiovascular risk factors associated with diabetes.
Keywords: Allopolyherbal formulation, Diabetes mellitus, OGTT model, Polyherbal formulation, Streptozotocin

Diabetes mellitus (DM) is one of the most severe,


incurable metabolic disorders characterized by
hyperglycaemia as a result of a relative, or an absolute,
lack of insulin, or the action of insulin on its target
tissue or both1. Besides hyperglycaemia, several other
symptoms, including hyperlipidemia, are involved in
the development of microvascular complication of
diabetes, which are the major causes of morbidity and
death2. It is a global public health problem, now
emerging as a world over epidemic. The number of
people with diabetes in India is currently around 40.9
million which is expected to rise to 69.9 million by
2025 unless urgent preventive steps not taken3.
Recently there has been a shift in universal trend
from synthetic to herbal medicine which can Return to
Nature as modern oral hypoglycaemic agents produce
undesirable side effects and herbal drugs/formulations
being preferred because of their effectiveness, minimal
side effects and relatively low cost4.
Management of diabetes without dyslipidemia and
various other associated side effects is still a challenge
to the medical community. Combination of allopathic

and herbal drugs can assist to overcome the resistance


due to insulin and/or oral hypoglycaemic therapy in
case of uncontrolled diabetes by reducing the dose of
allopathic drugs and their associated side effects.
There are so many oral hypoglycaemic drugs and
polyherbal formulations (PHFs) available in the
market but still diabetes is an uncontrolled disease, so
there is a need for alternative therapy for the
management of diabetes. An attempt has been made
to counteract the risk factors associated with chronic
oral hypoglycaemic drug by the new concept of
allopolyherbal formulation (APHF).
The literature survey also reveals that more than 50%
of polyherbal antidiabetic formulations available in the
market contain Trigonella foenum-graceum (Fenugreek,
Methi in Hindi), Momordica charantia (Bitter gourd,
Karela in Hindi) and Aegle marmelos (Wood apple, Bael
in Hindi) as one of their major components. Moreover,
these plants have been proved scientifically for their
antihyperglycemic and antihyperlipidemic, spasmolytic,
and digestive activities. They have different mechanisms
of action, therefore selected for the proposed study5-7.

____________
*Correspondent author
Telephone: 016363-324200 (O); +919915939996 (M)
E-mail: ankalia_47@rediffmail.com

Glipizide (GL) is one of the newest oral


hypoglycemic, effective and safe compound with
unique properties8.

MANIK et al: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECT OF ALLOPOLYHERBAL FORMULATION

Lyophilized extracts of Methi, Karela and Bael were


combined in different ratios to find out the best
antihyperglycemic combination and then the optimized
formulation based on preliminary screening using Oral
glucose tolerance test (OGTT) model, was combined
with GL as APHF in different doses and were used to
investigate their effect on blood glucose, body weight,
lipid profile, serum glutamic oxaloacetic transaminase
(SGOT) and serum glutamic pyruvate transaminase
(SGPT) in streptozotocin (STZ) induced diabetic rat
model.
Materials and Methods
ChemicalsSTZ was purchased from Sigma
Aldrich Co. (St Louis, MO, USA), GL was from USV
Limited (Mumbai, India) and the kits for glucose
determination; total cholesterol, triglycerides, high
density lipoprotein cholesterol (HDL-c), SGOT and
SGPT were purchased from Coral Company (Goa,
India). All other chemicals and reagents used were of
laboratory grade and were purchased from LDH,
Ranbaxy and MERCK etc.
Plant materialThe plant materials i.e. Methi
seeds, Karela fruits and Bael leaves were procured
locally, in the month of August and were
authenticated by Dr. Adarsh Pal, Head, Department of
Botanical and Enviornmental Sciences, Guru Nanak
Dev University, Amritsar (Punjab) and voucher
specimens were deposited in the department for future
reference.
Extraction and lyophilizationAll the drugs were
dried, coarsely powdered and stored in a closed
container. Dried powder of Methi was defatted with
petroleum ether and then extracted by triple
maceration with 70% ethanol whereas dried powder
of fruit and leaves of Karela and Bael were extracted
with 50 and 70% ethanol respectively using triple
maceration. These extracts were concentrated under
vacuum, deep freezed for overnight and were
lyophilized.
Development and optimization of polyherbal (PHF)
and allopolyherbal (APHF) formulationThe PHF
were developed by combining the lyophilized extracts
of selected plant materials in different experimental
ratios keeping Methi at constant ratio (Table 1) and
were optimized on the basis of OGTT study in normal
rats. The APHF were developed by mixing the
optimized PHF and GL in different experimental ratios
and optimized using OGTT studies in diabetic rats. The
optimized APHF was further evaluated by OGTT in
STZ-induced diabetic rat model.

703

AnimalsWistar rats (either sex) weighing


180-220 g were procured from the animal house of
I.S.F. College of Pharmacy, Moga (Reg. No.
816/PO/a/04/CPCSEA). The animals were kept in
polypropylene cages (3 in each cage) at an ambient
temperature of 252 C and 55-65% RH. A 12-12 h
light and dark schedule was maintained in the animal
house. The rats had free access to water and were fed
with commercially available feed. The protocol of the
experiment (IAEC/CPCSEA/2011/17) was approved
by Institutional Animal Ethics Committee and were
conducted in accordance with guidelines as per
Guide for the care and use of laboratory animal
and with permission from Committee for the Purpose
of Control and Supervision of Experiments on
Animals (CPCSEA).
Pharmacological screening
Optimization of PHF

Antihyperglycemic study in oral glucose tolerance


(OGTT) model in normal rats9Overnight fasted
normal rats were divided into 6 groups of 6 animals in
each. Gr. I Normal control (0.5% CMC solution); Gr. II
to IV were of different combination (PHF-A, PHF-B,
PHF-C)-1000 mg/kg b. wt; Gr. V PHF-B (500 mg/kg
body wt) and Gr. VI standard GL (10 mg/kg body wt).
The single dose of each prepared combination was
administered orally in the rats. All animals received
glucose (2 g/kg) orally after an hour of drug treatment.
The blood samples were withdrawn by retro-orbital
plexus under mild anaesthesia before administration of
the test drug-basal and at 0, 60 and 120 min after
glucose administration, the serum glucose was
estimated by glucose oxidase-peroxidase method10.
Induction of diabetesDiabetes was induced by a
single intra-peritoneal injection of freshly prepared
STZ (50 mg/kg body wt) in 0.1M citrate buffer (pH
4.5) to overnight fasted rats. STZ injected rats were
allowed to drink 20% glucose solution for 24 h to
prevent STZ-induced hypoglycaemic mortality11. The
development of diabetes was confirmed after 1 week
of STZ injection, the animals with fasting blood
Table 1Preparation of the polyherbal combination
Name of the formulation
Polyherbal formulation A
(PHF-A)-1000 mg/kg body wt.
Polyherbal formulation B
(PHF-B)-1000 mg/kg body wt.
Polyherbal formulation C
(PHF-C)-1000 mg/kg body wt.

Ratio of the plant material


Methi
Karela
Bael
2
1
2
2

INDIAN J EXP BIOL, SEPTEMBER 2013

704

glucose level more than 200 mg/dL were selected for


the present study12.
Optimization of the APHF

Antihyperglycemic study in oral glucose tolerance


test (OGTT) model in diabetic rats9Overnight
fasted diabetic rats were divided into 4 groups of 6
animals in each. Grouping of the animals was done as
mentioned below:
Gr. I Diabetic control (0.5% CMC solution); Gr. II
APHF A (500+5 mg/kg body wt); Gr. III APHF B
(750+5 mg/kg body wt) and Gr. IV GL (10 mg/kg
body wt).
Antihyperglycemic studies of optimized APHF in
STZ induced diabetic rat modelOn the basis of
OGTT studies in normal and diabetic rats dose was
selected for the STZ-induced diabetic rat model.
Experimental designAll diabetic rats were
randomly divided into following 5 groups of 6 each:
Gr. I
: Normal control (0.5% w/v CMC sol.)
: Diabetic control (0.5% w/v CMC sol.)
Gr. II
Gr. III : APHF A (500 mg/kg b. wt PHF-B+ 5 mg/kg
body wt GL)
Gr. IV : APHF B (750 mg/kg b. wt PHF-B+ 5 mg/kg
body wt GL)
Group V : GL 10 mg/kg body wt
All the test drugs were suspended in a vehicle
containing 0.5% (w/v) CMC in distilled water and
administered orally using an intra-gastric canula once
daily for 20 days.
The body weight of the animals was measured at
the onset of the study and at the regular intervals of
every week up to 21 days13.
The blood samples were collected on 0, 7, 14, 21
days of the study by puncturing the retro-orbital
plexus under mild anaesthesia. Serum was separated
by centrifugation at 3000 rpm for 15 min and used for

the estimation of glucose (GOD/POD method)10, total


cholesterol (CHOD/PAP method), total triglycerides
(TG) by GPO/PAP method, LDL-c, VLDL-c
(Freidewalds formula), and HDL-c levels (PEG
Precipitation method)14-17 Hepatic enzymes SGOT
and SGPT were determined using UV spectrometer18.
Postprandial studiesThe dose of APHF showing
the best antidiabetic activity in STZ-induced diabetic
rat model was selected for this study. Diabetic rats
fasted overnight were divided into four groups of six
rats each. Group I and III served as control (0.5% w/v
CMC sol.) and group II and IV received APHF B
(750 mg + 5 mg/ kg body wt).
In group I and III dose was given after meal and to
group II and IV it was given before meal. SGL was
taken initially and then food was given to the rats for
1 h and then dose was given after meal and before
meal to the respective groups and SGL was checked
at 2, 3 and 5 hrs after food administration.
Statistical analysisResults are presented as
meanSD. The statistical analysis involving two
groups was evaluated by means of two-way ANOVA
followed by Bonferroni post-test whereas one-way
ANOVA followed by Tukey post-test was used for
column analysis and P values (P<0.001 and P<0.05)
were considered to be significant.
Results and Discussion
Optimization of the formulation using OGTT normal
rat modelThe results showed 44.64 and 17.66% rise
in serum glucose level (SGL) after one hour of glucose
administration in vehicle control and GL (10 mg/kg b.
wt) pretreated groups, respectively. Whereas, group of
animals pretreated with the developed formulation
(PHF-A, PHF-B and PHF-C at the dose of 1000 mg/kg
b. wt, have shown rise in SGL by 28.26, 18.44 and
24.82%, respectively in comparison to 0 h (Table 2),

Table 2Effect of PHFs on serum glucose levels in OGTT model in normal rats
[Values are meanSD from 6 rate in each group. Figure in parentheses are % increase over O min values]
Groups
Normal control
PHF A (1000 mg/kg body wt)
PHF B (1000 mg/kg body wt)
PHF C (1000 mg/kg body wt)
PHF B (500 mg/kg body wt)
GL (10 mg/kg body wt)
a

Serum glucose levels (mg/dL


Basal
91.334.01
92.154.75
91.333.62
90.133.29
89.454.34
93.154.15

0 min
92.453.75
91.253.15
88.252.94
89.332.62
87.214.01
93.003.01

P< 0.001 vs normal vehicle control group. GL = Glipizide.

60 min
135.663.49 (44.64)
117.004.08 (28.26) a
105.003.01 (18.44) a
110.004.78 (24.82) a
110.004.15 (25.13) a
109.663.69 (17.66) a

120 min
99.253.16
96.663.85
93.753.75
94.002.16
94.373.75
95.002.63

MANIK et al: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECT OF ALLOPOLYHERBAL FORMULATION

on the basis of results PHF-B was administered at the


dose of 500 mg/kg b. wt and have shown an increase
of 25.49% rise in SGL just at par with the 1000 mg/kg
b. wt dose of PHF-A & PHF-C, hence selected for
further study in STZ induced diabetic rat model.
However, all groups of animals almost normalize the
SGLs within two hours indicating that the pancreas of
animals was healthy to clear out the glucose load from
the body. The result of OGTT study had shown that
PHF-B consisting of Methi, Karela and Bael (2:2:1)
have maximum antihyperglycemic activity even at par
with the standard drug. This is because of Methi and
Karela in the higher ratio, possessing insulin
modulation action and extra-pancreatic effects such as
the regulation of glucose uptake from the intestinal
lumen by the inhibition of carbohydrate digestion by
Methi19; acting like insulin or promoting insulin
release by Karela20 as well as the synergistic effect of
the Bael for its extra-pancreatic effect7. Therefore,
PHF-B was selected for further study in combination
with GL in diabetic rats.
Optimization of the APHF using OGTT diabetic rat
modelVehicle treated group and GL (10 mg/kg
body wt) showed 62.02 and 33.6% increase,
respectively in SGL at 1 h after glucose
administration whereas, APHF A (500 mg+5 mg/kg
body wt) and APHF B (750 +5 mg/kg body wt)
showed 30.52 and 27.52% rise, respectively in SGLs
at 1 h compared to 0 h (Table 3). The results showed
that APHF combinations (A, B) have significantly
improved glucose tolerance in glucose induced
hyperglycaemia in comparison to PHF-B (500 and
1000 mg/kg body wt). This is because of the presence
of GL, as it has rapid absorption and onset of action, it
further have potentiated the insulin action. Its insulin
action is associated with an increase in plasma
membrane insulin receptor number, involves some
post receptor events, and is significantly greater on
peripheral uptake of glucose than suppression of

hepatic glucose production.21 However, when


compared with standard drug its activity was at par
with GL (10 mg/kg body weightt) Hence, our concept
of the development of the APHF has been achieved
and it was selected for further chronic study in STZ
induced diabetic rats.
Effect of APHF on serum glucose level and other
parameters of diabetic ratsDiabetic control rats
showed consistent and gradual rise in the fasting SGL
during the study. GL, (10 mg/kg body wt), APHF-A
(500+5 mg/kg body wt) and APHF-B (750+5 mg/kg
body wt) treated rats showed a reduction in SGL by
20.07, 34.49 and 47.08 %; 23.35, 39.39 and 49.20 %;
27.56, 42.15 and 54.40 % on 7th, 14th and 21st day of
the study, respectively as compared to onset of the
study and the results were found to be statistically
significant (P<0.001) as compared to diabetic control
group (Table 4).
The effect was found to be time dependent up to 21
day of the study. Decrease in SGL was more
significant (P<0.001) on 21st day in comparison to
14th and 7th days. The effect of developed APHF was
significant (P<0.001) when compared with standard
drug. This effect of APHF on SGL was due to the
synergistic effect of PHF and of GL. The PHF might
be due to the regeneration of cell in presence of
Methi22, Bael23 and preventing the death of cell by
Karela24. However, no significant difference was
observed when the results were compared between
high and low doses of APHF (Table 4). Hence, the
lower dose of APHF (500 + 5 mg/kg body wt) is
recommended for the management of SGL.
Body weightTable 5 shows the average body
weights of animals on 21st day. Reduction in body
weight was observed in diabetic animals. However,
animals treated with APHF A, APHF B and GL
registered the significant (P<0.001) check on the loss
of body weight on 21st day in comparison to onset day
of the study. This effect may be attributed to increased

Table 3Effect of APHF on serum glucose levels in OGTT in diabetic rats


[Values are meanSD from 6 rats in each group. Figures in parentheses are % increase of serum glucose lever
over O min values]
Groups
Diabetic control
APHF A (500 mg+5 mg/kg body wt)
APHF B (750 mg+5 mg/kg body wt)
GL (10 mg/kg body wt)
a

P< 0.001 vs diabetic control group.

Serum glucose levels (mg/dL)


Basal
237.662.05
249.333.09
214.504.50
245.373.15

705

0 min
240.663.01
204.663.39
165.853.15
206.122.17

60 min
391.003.81 (62.02) a
268.003.55 (30.52) a
212.503.01 (27.52) a
275.452.84 (33.60) a

120 min.
301.332.34
221.004.32
174.504.01
228.423.75

INDIAN J EXP BIOL, SEPTEMBER 2013

706

insulin secretion and food consumption25, 26; increased


GLUT-4 transporter protein of muscles and increased
glucose utilization in the liver and muscle by Karela20.
Lipid profile and hepatic enzymesAfter 21 days of
the study, animals of the diabetic control group showed
a significant (P<0.05) rise in serum cholesterol, TG,
LDL-c, VLDL-c, SGOT and SGPT levels, whereas,
significant reduction (P<0.05) was seen in serum HDLc in comparison to normal rats. The animals treated
with GL, APHF A and APHF B showed significant
(P<0.05) check on these abnormal levels of cholesterol,
TG, LDL-c, VLDL-c, SGOT and SGPT levels and

HDL-c levels in comparison to diabetic animals (Table


5). The developed APHF has proved to be more
effective in improving lipid metabolism as compared to
GL because Bael exerts its action by interfering with
the biosynthesis of cholesterol and utilization of
lipids27, hypo-cholesterolemic effect of Karela20 and
Methi seeds increase biliary cholesterol excretion in
liver due to sapogenins28 and the lipotropic effect of the
lecithin22. These results implied that developed
formulation can reduce the complications of lipid
metabolism and associated cardiovascular risk factors
during diabetes.

Table 4Effect of 20 days treatment of APHF on serum glucose levels of STZ-induced diabetic rats.
[Values are meanSD from rats in each group. Figures in parentheses are % increase of serum glucose level
over O day values]
Groups

Serum glucose levels (mg/dL)


0 day

Normal group
Diabetic control
APHF A (500 mg+5 mg/kg body wt)

7 day

14 day

21 day

85.165.98
262.135.01
250.835.53

85.006.05
84.664.85
86.166.07
271.536.13a
293.225.23a
310.106.53a
189.506.99
149.336.03
122.337.90
(23.35) abc
(39.39) abc
(49.20) abc
APHF B (750 mg+5 mg/kg body wt)
254.836.05
181.837.13
145.165.74
112.506.45
(27.56) abc
(42.15) abc
(54.40) abc
GL (10 mg/kg body wt)
267.005.29
211.336.30
169.668.71
138.006.08
(20.07) ab
(34.49) ab
(47.08) ab
a
b
c
Pvlaues: <0.001; Vs normal control group; diabetic control group; cGL treated group Figures in parentheses
are % decrease of serum glucose level over 0 day values.
Table 5Effect of APHF treatment on body weight, serum lipids and hepatic enzymes in STZ-induced diabetic rats on 21 day
[Values are meanSD from 6 rats in each group. Figures in parentheses are % increase/decrease]
Parameters

Groups
Normal
control

Diabetic
control

Body weight (g)

209.805.96

Cholesterol (mg/dL)

96.455.38

TG (mg/dL)

61.536.01

HDL-c (mg/dL)

42.354.01

VLDL-c (mg/dL)

12.454.15

LDL-c (mg/dL)

42.724.63

SGOT (U/L)

25.473.15

SGPT (U/L)

27.384.01

105.126.83
(45.12%)*
250.106.3
(151.79%)a
142.375.10
(118.34%)a
21.374.01
(45.25%)a
27.574.53
(93.37%)a
201.535.75
(337.76%)a
82.122.15
194.40%)a
79.373.78
164.89%)a

Pvalues: *<0.001, a<0.05 vs normal group


#<0.001, b<0.05 vs diabetic group
$ <0.001, c<0.05 vs Glipizide group

APHF-A
APHF-B
GL
(500 mg+5 mg/kg bdy wt) (750 mg+5 mg/kg body wt) (10 mg/kg body wt)
165.227.23
(17.54%)*#$
122.136.57
(49.80%)ab
92.476.75
(32.71%)ab
31.756.01
(48.77%)ab
19.733.15
(28.72%)ab
69.733.75
(64.55%)abc
23.153.23
68.69%)bc
24.494.17
65.53%)b

158.125.15
(15.18)*#$
112.475.20
(54.10%)abc
80.127.01
(40.91%)abc
40.533.15
(72.12%)bc
16.154.32
(36.23%)b
54.383.79
(71.93%)abc
15.474.15
(76.71%)abc
17.013.78
74.99%)abc

143.345.01
(19.87)*#
130.737.01
(46.27%)ab
95.347.34
(30.37%)ab
27.575.34
(29.66%)a
20.473.25
(26.10%)ab
79.134.10
(59.24%)ab
29.143.78
(59.84%)b
29.784.01
(59.36%)b

MANIK et al: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC EFFECT OF ALLOPOLYHERBAL FORMULATION

707

Table 6Effect of APHF on serum glucose levels on postprandial studies in diabetic rats
[Values are meanSD from 6 rats in each group. Figures in parentheses are % increase of serum glucose level over O day values]
Groups
Dose administered after meal
Diabetic control group
APHF D
(750+5 mg/kg body wt.)

Serum glucose levels (mg/dL)


Basal

2h

3h

5h

204.002.94

302.332.05
(47.08)
257.453.01
(25.28)a

283.003.01
(38.20)
245.152.15
(18.95)a

268.662.86
(31.20)
230.753.15
(12.50)a

355.352.75
(40.34)
275.753.15
(14.29)a

311.753.45
(23.53)
252.272.75
(4.51)a

290.682.86
(15.04)
237.152.15
(1.93)a

205.152.75

Dose administered before meal


Diabetic control group

252.003.15

APHF D
(750+5 mg/kg body wt.)

240.004.01

P< 0.001 vs diabetic control group.

Hepatotoxicity is another risk factor associated


with oral hypoglycemics treatment on long term use.
This risk factor can be minimized by reducing the
dose of oral hypoglycemics in combination with
herbal drugs. Karela and Bael have been already
proved as hepatoprotective agents29,30. The APHFs (A,
B) exhibited better results than GL in the
improvement of hepatic enzymes SGOT and SGPT
levels (Table 5) indicating that the liver damage is to
a less extent in rats treated with APHFs than with GL
alone (10 mg/kg body wt).
Effect of APHF on postprandial studies in diabetic
ratsThe postprandial study in diabetic animals have
shown that the developed APHF is more effective if it
is given before food, which may be due to the
medication of enhanced insulin secretion by Bael and
the results were found to be significant (P<0.001) as
compared to respective diabetic control group
(Table 6). This effect may be due to the insulin
secretagogue effect by Bael; insulino-mimetic effect
of Karela and glucosidase enzyme inhibitory effect
of Methi. Moreover, blood glucose lowering effect of
the developed formulation is improved when it was
given before meal.
Toxicity studyThroughout the period of study,
animals treated with developed APHFs did not show
any behavioural changes and mortality as evident
from results showing normal hepatic functions,
therefore on this basis no separate toxicity studies
were carried out.
Conclusion
The postprandial study in diabetic animals have
shown that the developed APHF is more effective if it

is given before food, which may be due to the


mediation of enhanced insulin secretion by Bael,
inhibition of alpha amylase enzyme by Methi31 and
insulin like effect of Karela. Moreover, blood
glucose-lowering effect is improved when GL is
given before meal32 (Table 6).
The developed APHFs at lower dose of (500 mg/kg
body weight PHF + 5 mg/kg body wt GL) is
recommended for the management of diabetes and its
complications as it was found to be more effective
than standard drug GL (10 mg/kg body wt) alone and
the side effects associated with GL can be reduced as
its dose is reduced. There was no behavioural toxicity;
hepato-toxicity and mortality have been observed
during the complete duration of study. Hence,
developed APHF may be an ideal alternative for the
existing antihyperglycemic formulations with an
additional advantage of antihyperlipidemic effect and
minimizing the cardiovascular risk factors associated
with diabetes mellitus, hence, the concept has been
achieved.
It may be concluded that these findings will open a
new vista in the area of medical science for
the development of therapeutic approach for
the management of diabetes by simultaneous
administration of polyherbal formulation and synthetic
drug as this approach has reduced the dose, side effects
and adverse biological interaction of synthetic drug.
Acknowledgement
Thanks are due to Prof. P. L. Sharma, Head,
Department of Pharmacology for criticism and Shri
Parveen Garg (Chairman, ISFCP, Moga) for
infrastructure.

708

INDIAN J EXP BIOL, SEPTEMBER 2013

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