CHAPTER 1

THE PROBLEM AND ITS BACKGROUND This chapter includes the introduction about traditional medicines, impact of diabetes mellitus in the society, as well as medicinal contribution of mango plant. The statement of the problem, objectives of the study, hypothesis, theoretical and conceptual framework, assumptions, significance of the study, scope and delimitation, and the definition of key terms were also included.

Introduction Diabetes Mellitus is defined as an elevated blood glucose associated with absent or inadequate pancreatic insulin secretion, with or without concurrent impairment of insulin action. The disease states underlying the diagnosis of diabetes mellitus are now classifiedinto four categories: type 1, insulindependent diabetes, type 2, non-insulin-dependent diabetes, type 3, other, type 4, gestational diabetes mellitus. Over time, diabetes can lead to blindness, kidney failure, and nerve damage. These types of damage are the results of damage to small vessels, referred to as microvascular disease. Diabetes is a also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other large blood vessel diseases. Diabetes is usually associated with hypertension, poor metabolic control, smoking and obesity.

Modern medicines like biguanides, sulphonylureas and thiozolidinediones are available for the treatment of diabetes. But they also have undesired effects associated with their uses. Alternative medicines particularly herbal medicines are available for the treatment of diabetes. Common advantages of herbal medicines are effectives, safety, affordability and acceptability. Medicinal plants and their products have been used in the Indian traditional system of medicine and have shown experimental or clinical anti-diabetic activity. Medicinal Plants are a rich source of natural products. Medicinal plants and their products have been widely used for treatment of diabetic populace all around the world with less known scientific basis of their functioning. Leaf of Mangifera indica L., commonly known as mango (Family; Anacardiaceae) is large evergreen tree of tropical and subtropical region has been used by traditional medicine of a number of peoples for centuries. In Ayurvedic literature of India, different parts of this plant have been recommended as a remedy for various ailments like antidiabetic, anti-oxidant, antiviral, cardiotonic, hypotensive, anti-inflammatory properties, various effects like antibacterial, anti fungal, anthelmintic, anti parasitic, anti tumor, anti HIV, antibone resorption, antispasmodic, antipyretic, antidiarrhoeal, antiallergic, immunomodulation, hypolipidemic, anti microbial, hepatoprotective, gastroprotective. The aqueous extract of the leaves of M. indica possess hypoglycaemic activity. The natural C-glucoside xanthone mangiferin [2-C-Dgluco-pyranosyl-1,3,6,7- tetrahydroxyxanthone;C19H18O11; Mw, 422.35;

melting point, anhydrous 271C has been reported in various parts of M. indica leaves.

Statement of the Problem The main problem of this study is to determine the hypoglycemic activity between the positive control (Metformin) and the experimental group (Mangiferin contain in the leaves extract of Mangifera Indica) in treating alloxan- induced diabetic mice, it attempts to answer the following research question: 1. What are the constituents of ethanol Leaves extract of Mangifera Indica responsible for being stated as antihyperglycemic agent? 2. What is the most important action of Mangifera Indica in treating diabetes? 3.Is there any significant differences between the Positive Control and the Experimental Group in treating alloxan-induced diabetic mice? 4.Is there any significant differences between the Negative Control and the Experimental Group in the level of glucose in blood serum diabetic mice?

Objectives of the Study The main purpose of this study is to determine the hypoglycemic activity between the positive control (Metformin) and experimental group (Mangiferin) in treating alloxan-induced diabetic mice. Specifically, it attempts to answer the following objectives:

1. To identify the constituents of ethanol-leaves extract of Mangifera indica responsible for being stated as anti-hyperglycemic agent. 2. To find out the most important action of Mangifera indica in treating diabetes. 3. To determine the significant differences between the Positive Control and the Experimental Group in treating alloxan-induced diabetic mice. 4. To determine the significant differences between the Negative Control and the Experimental Group in treating alloxan-induced diabetic mice.

Hypothesis Based on the foregoing research problems, the researcher formulated the following null hypothesis: 1. The leaves of Mangifera Indica was reported that rich in Mangiferin, a xanthone glycoside. 2. Ethanol extract of M. Indica was tested for antidiabetic activity might be due to a systemic action, i.e. as a result of the stimulation of pancreatic Bcells and improving the insulin secretory capacity or enhancement of insulin action by the extract. 3. There is no significant difference between the positive control and the experimental group related in the action taken in treating diabetic mice. 4. There is a significant difference between the Negative Control and the Experimental Group in level of blood glucose level in diabetic mice.

Theoretical and Conceptual Framework

INPUT

PROCESS

OUTPUT

Mango leaf extract Extract Concentration 50% of the Mango leaf extract 75% of the Mango leaf extract 100% of the Mango leaf extract Normal Control Healthy mice Positive Control drugs Healthy mice will be administered Alloxan to make diabetic. Induced-diabetic mice will be administered a dose of Metformin (150mg/kg) Negative Control Drugs Healthy mice will be administered Alloxan to make diabetic. Induced diabetic mice will be administered NSS Experimental Group Healthy mice will be administered Alloxan to make diabetic. Induced-diabetic mice will be administered a different dose of Mangiferin (150 mg/kg)

Confirmatory Test of the physiological active constituent.

Present of Active Constituents such as Alkaloid, Phenolic Compound, Flavonoids

Determination of Blood Glucose Level in Serum of Albino Mice extracted in tail vein The Baseline Blood Sugar Level (BSL) will be measured and recorded after 15 mins, 30 mins, & 1 Hour.

Positve for hypoglycemic activity as shown by the significant lowering Fasting plasma Glucose Level at different time intervals in Alloxan-induced diabetic mices.

Figure 1. This paradigm describes the hypoglycemic property or activity of the Mangifera Indica Extract (MIE) applied to albino mice and the outcome of the test.

Assumptions The following assumptions serve as asses for the present study: 1. The Mangifera Indica is a safe and effective as hypo-/hyperglycemic agent and no severe undesirable effect. 2. The Mangifera Indica encourages the individual to become herbal users rather than drug users. 3. The Mangifera Indica can decrease the over-growing diabetic patient in the country. 4. The aqueous leaf extract of Mangga contain an active constituents that may exhibit hypoglycemic activity.

Significance of the Study The main purpose of this study is to investigate hypo- / hyperglycemic effects of Mangifera Indica leaf extract in diabetic mice. Alloxan was used to induce diabetic mice.

This study is important to the following;

Students: In the field of Pharmacy, the study will serve as added information on related studies using Mangifera Indica. The study will also serve as future reference for next generation of Pharmacy. Community: The study promotes the value and utility of the Mango Leaves instead of discarding them; also help the society to educate about the medicinal use of Mango Leaves due to its hypoglycemic effect. Researchers: The study will contribute to the references of the local health researchers of the different agencies of the government particularly the Department of Science and Technology (DOST). Government: The study can contribute in programs and project of the Philippine Government regarding the promotion of traditional medicines as alternative medication, especially to patients who cannot afford to buy expensive medicines. Economy: The study can make economy progress from producing medications from natural resources that will minimize importation of expensive medication.

Scope and Delimitations of the Study The study will be limited only to the evaluation of hypo-/antihyperglycemic action of ethanol leaves extract of Mangifera Indica Linnin the alloxan induced diabetic mice. This will be conducted at Our Lady of Fatima University Pharmacy Laboratory in the first and second semester of school year 20112012.

The materials to be used in this study were leaves of Mango, test animals (albino mice), Metformin (positive control) and alloxan (induced-diabetic drug). There were 6 diabetic mice, which divided into 3 groups. First three diabetic mice will administer Mango Extract, serve as our experimental group. The second group, were three diabetic mice that will administer Insulin, positive control. The third group was three mice serve as normal mice, neither treated Mango Extract nor Metformin. And the last group was three diabetic mice that will serves as our diabetic control.

The blood-glucose level of the Positive mice, diabetic mice and experimental mice will be monitored by using any of these following Biochemical parameters: fasting blood sugar (FBS), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) levels and high-density lipoprotein (HDL) level in blood serum were measured.

Findings of the study would be based only to these experiments. Through these could be used as base for similar studies that would conducting using different materials and method.

Definition of Key Terms

Albino Mouse. : An albino form of the house mouse, widely bred as a pet and laboratory animal. Alloxan. : An oxidized product of uric acid that tends to destroy the islet cells of the pancreas, thus producing diabetes (alloxan diabetes). Antihyperglycemic. : An agent that counteracts high levels of glucose in the blood Blood Sugar. : Glucose occurring in the blood, or the amount of glucose in the blood. Blood Glucose Level. : Level of glucose in the bloodstream, normally about 70 to 115 mg/dL after fasting overnight. Higher levels may indicate diseases such as diabetes mellitus. Crude Extract. : A concentrated preparation of a drug obtained by removing the active constituents of the drug with suitable solvents, evaporating all or nearly all of the solvent, and adjusting the residual mass or powder to the prescribed standard. Decoction. : A liquid medicine made from an extract of water-soluble substances, usually with the aid of boiling water. Herbal remedies are usually decoctions. Diabetes Mellitus.: Is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both Experimental Group. : consists of four (4) albino mice, which were administered with Mangifera Indica (Mangga) leaves extract

Extract. : This refers to the concentrated preparations of vegetable or animal drugs obtained by removal of the active constituents of the respective drugs with suitable solvents, evaporating of all nearly all of the solvent, and adjusting of the residual masses or powders to the prescribed standards. Glycoside. : Any of a group of organic compounds, occurring abundantly in plants, that yield a sugar and one or more nonsugar substances on hydrolysis. Hyperglycemia. : The presence of an abnormally high concentration of glucose in the blood. Hypoglycemic agent. :Any of various agents that decrease the level of glucose in the blood and are used in the treatment of diabetes mellitus Metformin. : An oral antidiabetic agent that decreases glucose production by the liver and lowers plasma glucose levels Metformin Resistance. :The capacity of an organism or a tissue to withstand the effects of Metformin. Organoleptic Evaluation.: This refers to the physical evaluation of a sample by the use of different body senses. Phytochemical. : It is also phytonutrient or any of various bioactive chemical compounds found in plants considered to be beneficial to human health. Positive Control Group.: It refers to the four (4) albino mice which were administered with Metformin.

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