IJRPC 2011, 1(3)
Sagar et al.
ISSN: 22312781

Available online at www.ijrpc.com

Research Article
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

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
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
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 bael fruit in combination with metformin in normal rabbits as a preliminary investigation. 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 tent/33/suplement1/s3.full.Retrived 2010-01-29. Mortality in a National Sample of U.S. Adults. Diabetes Care. 2001; Morrison K, Gerstein H, Raina P, Booker L and Yazid H. Diagnosis, Majumadar SR, Tsuyuki RT, Varey J and Johnson JA. Benefits and Harms of Anti Diabetic Agents in Patients with Diabetes and Heart Failure: Glucose Concentration, and Risk of Vascular Disease. A Collaborative Chandrasekhar K, madhusudhan RC, Madhusudhan Cephalexin on the Pharmacokinetics of Metformin in Healthy Human Leaf and Callus of Aegle marmelod in Rabbit, Short. Science Asia. Based on a thorough Systematic Review of the Available Scientific Complementary Therapies on the Professional

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