IJRPC 2011, 1(3) Sagar et al. ISSN: 22312781 INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACY AND CHEMISTRY Available online at www.ijrpc.com Research Article BENEFICIAL EFFECT OF ETHONOLIC EXTRACT OF BAEL FRUIT IN COMBINATION WITH METFORMIN HCL IN NORMAL VIDYA SAGAR K*, SHIVA KRISHNA N, SRIPATHI BN, TEJA SRUTHI PVR, RAMANA REDDY K, SUNITHA P, SRIKANTH P
Dr. Samuel George Institute of Pharmaceutical Sciences, Markapur, Prakasam
*Corresponding Author: sagar951@gmail.com
ABSTRACT
Diabetes mellitus is a chronic disease, Metformin an allopathic drug used in the treatment of
diabetes as it causes side effects to reduce such side effects ethonolic bael extract a herbal
drug which has no side effects is used with combination of metformin. The influence of
single drug and multiple drug effect of the selected drugs on hypoglycemic activity were
studied in normal rabbits. Rabbits were selected as suitable animal models for the study of
the above parameters since adequate quantities of blood samples can be collected at the
desired intervals of time. The selection of the rabbits in the study also represents non-rodent
model apart from ease of collection of sufficient volume of blood sample. In this study we perform about the hypoglycemic effect of the ethonalic bael extract and metformin
hydrochloride, individually and in combination in normal rabbits. Here we maintained same group of animals with appropriate wash out periods.
Keywords: Diabetes mellitus, Ethanolic bael extract, Hypoglycemia, Metformin hydrochloride. INTRODUCTION DIABETES MELLITUS Diabetes mellitus, often simply referred to as diabetes—is a group of metabolic diseases in
which a person has high blood sugar, either
Type 1 Diabetes
because the body does not produce enough
Type 1 diabetes mellitus is characterized by
insulin, or because cells do not respond to the
loss of the insulin-producing beta cells of the
insulin that is produced. This high blood sugar
islets of Langerhans in the pancreas leading to
produces the classical symptoms of polyuria
insulin deficiency. This type of diabetes can be
(frequent urination), polydipsia (increased
further classified as immune-mediated or
thirst) and polyphagia (increased hunger).
idiopathic. The majority of type 1 diabetes is of
the immune-mediated nature, where beta cell
loss is a T-cell mediated autoimmune attack.[1]
There is no known preventive measure against
Lanka, Burma, and Thailand. The tree is a
type 1 diabetes, which causes approximately
slender, aromatic perennial, 6.0–7.5 m tall and
90–120 cm in girth. It flowers from May to July
affected people are otherwise healthy and of a
and yields an annual average of 300–400 fruits
healthy weight when onset occurs. Sensitivity
(200–250 kg) per tree. Various parts of the tree,
and responsiveness to insulin are usually
normal, especially in the early stages. Type 1
diabetes can affect children or adults but was
possesses a hypoglycemic effect. The incidence
of diabetes is increasing. The effect of an
because it represents a majority of the diabetes
aqueous extract of Aegle marmelos fruits on
Type 2 Diabetes Metformin is an oral ant diabetic drug in the
Type 2 diabetes mellitus is characterized by
biguanide class. It is the first-line drug of
insulin resistance which may be combined
choice for the treatment of type 2 diabetes, in
with relatively reduced insulin secretion. The
particular, in overweight and obese people
defective responsiveness of body tissues to
and those with normal kidney function.[1][2][3]
insulin is believed to involve the insulin
Evidence is also mounting for its efficacy in
receptor. However, the specific defects are not
gestational diabetes, although safety concerns
still preclude its widespread use in this
defect are classified separately. Type 2
setting. It is also used in the treatment of
diabetes is the most common type. There is no
investigated for other diseases where insulin
diabetes, which causes approximately 90%-
95% of diabetes mellitus cases. In the early
stage of type 2 diabetes, the predominant
diabetes however is increasingly being used in
abnormality is reduced insulin sensitivity. At
polycystic ovary syndrome (PCOS),[10] non-
this stage hyperglycemia can be reversed by a
alcoholic fatty liver disease (NAFLD)and
variety of measures and medications that
premature puberty, three other diseases that
improve insulin sensitivity or reduce glucose
feature insulin resistance; these indications are
still considered experimental. The benefit of
Aegle Marmelos(Rutaceae) is a popular
metformin in NAFLD has not been extensively
medicinal plant in the Ayurvedic and Siddha
studied and may be only temporary; although
systems of medicine and folk medicines used
some randomized controlled trials have found
to treat a wide variety of ailments. The plant,
significant improvement with its use, the
popularly known as the bael tree, is native to
the Indo-Malayan region and is currently cultivated in India, Pakistan, Bangladesh, Sri
MATERIALS AND METHODS
The following drugs and other chemicals were used in the present study.
Aegle marmelos(Bael tree) extract
a beep sound will let you know that the test
Albino rabbits of either sex weighing between
1.30 and 1.75 kg obtained from the animal
3. In 10 seconds, the blood glucose value
house were used in the study. All the rabbits
were maintained on uniform weight of leafy
vegetable food and water. The animals were
maintained at 25±1 0C in 12h/12h light/dark
cycle. All the animals were fasted for 18 h before the experiment and water was
Preparation of Drug Solutions Bael solution Blood Glucose Testing Meter 250mg /kg body weight of bael extract was
The Eukare blood glucose testing strip is to be
weighed accurately and was dissolved in a
used with the EUKare blood glucometer to test
5ml/kg body weight using distilled water.
glucose levels in the whole blood. When the
blood sample is in contact with blood sample
Metformin Hcl Tablet Solution
inlet of the test strip, it will flow in to the reaction area automatically and start the test.
Only small amount of blood is needed (3µ/
one test). The testing range of blood glucose is
Testing Principles The therapeutic dose of metformin for rabbit
considering the safety of rabbits. The dose was
2. After filling up the reaction area, the
calculated according to equivalent factor of
metformin hydrochloride tablets 11.16mg/kg
body weight of tablet powder was dissolved
in 5ml/kg body weight using distilled water.
Administration of Drugs
4. The test strip is an electro chemical
The drugs were administered by oral route
with the help of oral feeding tube as described
below. The rabbit was fixed in rabbit holder
with its head protruding outside. Then a
mouth gag was introduced in between the two
5. Then the blood glucose meter releases
jaws and held in position by holding the upper
an electric current at a regular voltage,
jaw and lower jaw with left hand. Infant
on the surface of the test strip will be
introduced into the mouth through the central
hole of the mouth gag. The tube was pushed
6. The current detected will be converted
slowly such that it enters the oesophagus and
in to a special formula built inside the
reaches the stomach. To the other end of the
administering 2 ml of distilled water to ensure
Testing Procedure
free flow into the stomach, the required
1. Insert the test strip into the test slot of
administered through the syringe and feeding
tube. This was followed by 5 ml of distilled
water to ensure the administration of the dose
2. Prick the ear vein with the needle and
of the drug accurately. The tube was removed
Single Drug Treatment with the Selected
drug administration. The blood samples were
Drug (SD)
collected into clean disposable centrifuge
All the four rabbits were observed in single
group. The experiment was conducted in four
immediately for blood glucose levels using
stages with one week washout period between
Stage-I Rabbits were administered with
collected at different time intervals (0-24hrs)
The glyceimic levels of the rabbit with vehicle
and were estimated for blood glucose. These
(water) used in experiment are observed.
results were used as control. After this stage
The average mean & standard deviation
values are mentioned in table number 1.0(A)
maintained and the rabbits were utilized for
The percentage reduction of blood glucose
levels are mentioned in Table number 1.0(B)
Stage-II Rabbits were treated with dose of
Bael extract and blood samples were collected
The glyceimic levels changes in the rabbit with
and analyzed for blood glucose serum levels.
After this stage seven days washout period
has been maintained and the rabbits were
The average mean& standard deviation values
Stage-III After seven days washout period,
The percentage reduction of blood glucose
the same groups of animals were treated with
levels are mentioned in Table number 1.1(B)
dose of metformin. After this stage seven days
washout period has been maintained and the
The glyceimic levels changes in the rabbit with
rabbits were utilized for further experiment.
Stage-IV After seven days washout period,
the animals were treated with combination of
The average mean & standard deviation
drugs in individual dose with 30mins gap of
values are mentioned in table number 1.2(A)
The percentage reduction of blood glucose
Collection of Blood Samples
levels are mentioned in Table number 1.2(B)
The blood samples were collected by pricking
the marginal ear vein. The veins were dilated
The glyceimic levels changes in the rabbit with
by warming the ears on a low voltage lamp or
Dose of Metformin tablet powder and bael
extract used in experiment are observed.
punctured with a surgical needle opposite to
The average mean & standard deviation
samples were collected in predose sample
The percentage reduction of blood glucose
and15min, 30min, 1,2,4,6,8,12 and 24 h after
levels are mentioned in Table number 1.3(A)
Reduction % Values of phase 0 Time(hr) Reduction% Values of phase 1 Reduction% Values of phase 2 Reduction% Values of phase 3 Graphical representation of comparison of% reduction of blood sugar levels of the rabbits DISCUSSION CONCLUSION
The present study in normal rabbits reveals
demands lifelong medication to maintain the
that the ethonolic extract of bael fruit haven’t
body’s glucose homeostasis with the aid of
shown any effect on blood glucose level on its
single/multiple drug therapy. It is well known
that the allopathic medications on long run
metformin, it tend to enhance its effect and
usage tend to cause side effects and even in
even extended its therapeutic value. So from
condition. Hence there is growing interest and
conclude that, ethonolic extract of bael fruit is
demand for the herbal drugs as supplements
to the therapy because of their no or less side
chronic therapy like diabetes mellitus by
effects even in chronic administration. Apart
which one can reduce the dose of metformin
from their fewer side effects they usually
required to maintain glucose homeostasis
posses multiple beneficiary effects such as
antioxidant and anti-inflammatory etc. Hence
antihyperglycaemic agents. To validate its
in many parts of the rural areas of india it has
become practice to use the herbal drugs in
combination with allopathic drug with or
prove it’s worthy to be used in long run.
without the consultation of the physicians for
many other ailing conditions. The present study focused to give sufficient scientific
REFERENCES
evidence in the usage of ethonolic extract of
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The ethonolic extraction of Aegle marmelos has
Metformin an allopathic drug had shown a
When ethonolic extract of bael fruit was
administered in combination with metformin
quite interestingly it shown synergistic action
sustained activity by increasing the rate of
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Wednesday October 31, 2012 Exodus 9:13 – 10:29 I. Who Are the Warrior Kings? A. Then Moses said to God, “If I come to the people of Israel and say to them, ‘The God of your fathers has sent me to you,’ and they ask me, ‘What is his name?’ what shall I say to them?” God said to Moses, ‘I AM WHO I AM.” 1. “In the beginning God created the heavens and the earth.” (Genesis