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 is a serious, chronic disease that occurs either when the pancreas

does not produce enough insulin (a hormone that regulates blood sugar, or

glucose), or when the body cannot effectively use the insulin it produces. Diabetes

is an important public health problem, one of four priority noncommunicable

diseases (NCDs) targeted for action by world leaders. Both the number of cases

and the prevalence of diabetes have been steadily increasing over the past few

decades.

Globally, an estimated 422 million adults were living with diabetes in 2014,

compared to 108 million in 1980. The global prevalence (age-standardized) of

diabetes has nearly doubled since 1980, rising from 4.7% to 8.5% in the adult

population. This reflects an increase in associated risk factors such as being

overweight or obese. Over the past decade, diabetes prevalence has risen faster

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in low- and middle-income countries than in high-income countries. Diabetes

caused 1.5 million deaths in 2012. Higher-than-optimal blood glucose caused an

additional 2.2 million deaths, by increasing the risks of cardiovascular and other

diseases. Forty-three percent of these 3.7 million deaths occur before the age of

70 years. The percentage of deaths attributable to high blood glucose or diabetes

that occurs prior to age 70 is higher in low- and middle-income countries than in

high-income countries.

Diabetes exerts a major impact in third-world countries, particularly in the

Philippines. It is said that Asia will see the greatest increase in the number of

people with diabetes by 2025. This increase in the burden of chronic diseases in

Asia will significantly affect nations' respective health care systems, both acutely

and chronically.

According to International Diabetes Federation (IDF), Philippines is one of the

22 countries and territories of the IDF Western Pacific Region. 425 million people

have diabetes in the world and 159 million people in the WP Region; by 2045 this

will rise to 183 million. There were over 3.721.900 cases of diabetes in Philippines

in as of 2017 which has a total adult population of 60,327,000, a prevalence of

diabetes among adults 6.2% and a total case of diabetes in adults of 3,721,900.

Diabetes mellitus is a metabolic disorder that is characterized by hyperglycemia

associated with impairment in insulin secretion and/or insulin action as well as

aberrations in intermediary metabolism of carbohydrates, proteins and lipids. The

effects of diabetes mellitus include long-term damage, dysfunction and failure of

various organs. Diabetes mellitus may present with classical characteristic

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features such as blurring of vision, excessive thirst (polydipsia), excessive feeding

(polyphagia) excessive urination (polyuria), and weight loss. In its most severe

forms, ketoacidosis may develop leading to stupor, coma and, in absence of

effective treatment death ensues.

The goals of therapy for diabetes consist of glycemic control by diet, lifestyle

modification, regular exercise, medication i.e., oral anti diabetic drugs and insulin

therapy to treat associated conditions like dyslipidemia, hypertension, obesity,

coronary heart disease and to screen for or manage complications of diabetes

like retinopathy, cardiovascular disease, nephropathy, neuropathy and other

complications.

Modern medicines like biguanides, sulphonylureas and thiazolidinediones 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.

Plants and their bioactive constituents are used for the treatment of diabetes

mellitus throughout the world; especially in countries where access to the

conventional treatment of diabetes mellitus is inadequate. Plants have been used

for food, medicine, building materials and fuel for many centuries until now. The

World Health Organization (WHO) noted that of the 119 plants derived

pharmaceutical drugs, 74 % are used in modern medicine in ways that correlated

directly with their traditional uses as Herbal plant medicine by native culture. WHO

estimated that about 80 % of the world population presently uses herbal medicine

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for some aspects of their primary health care needs while plant products also play

important roles in the health care system of the remaining 20%, who mainly reside

in developed countries.

There are various medicinal plants in the world, which are the potential sources

of the drugs. The discovery of the widely used hypoglycemic drug, metformin (N,

N• dimethylguanylguanidine) came from the traditional approach through the use

of Galega officinialis. Traditionally various plants are being used to treat diabetic

patients. It is believed that, herbal medicine has little side effects as well as it

requires no cost in few cases. Thus, it can solve the economic problem of the

poor. Now a day, the scientists and researchers are looking for natural plant

products by research all over the world and a large number of the evidence have

shown the immense potential of medicinal plants used traditionally. Therefore,

discovery and development of novel drugs for diabetes is still needed.

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. It is considered

as one of the main tropical fruits in the world believed to be originated from Asia.

It has been reported that China, India, Brazil, Nigeria, Pakistan, Mexico, Thailand,

and Philippine are well-known for mango cultivation with India being the highest

mango cultivating country. World production of mango is approximately 42 million

tons per year which is second only to banana production. There are about 1000

mango varieties grown all over the world.

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 The aqueous extract of the leaves of M. indica possess hypoglycaemic activity.

The natural C-glucoside xanthone mangiferin [2-C-β-Dgluco-pyranosyl-1,3,6,7-

tetrahydroxyxanthone; C19H18O11; Mw, 422.35; melting point, anhydrous 271°C

has been reported in various parts of M. indica leaves, which possesses

pharmacological effects, that is, antidiabetic, antioxidant, antimicrobial, anticancer,

and anti-inflammatory properties. It is a rich source of various polyphenolic

compounds, especially C-glucoside xanthone mangiferin [see Figure 1], which is

the major component that can be detected in all parts of the mango. This

compound is a xanthone derivative that referred as super antioxidant. It also has

been found for pharmacological effects including antioxidant, radioprotective,

antiallergic, antidiabetic, anticancer, antimicrobial, immunomodulatory, and anti-

inflammatory activities.

In the Philippines, Manga (local name) is a large tree, with a dense and

spreading crown. It is the national fruit of Philippines. Leaves are oblong to oblong-

lanceolate, 10 to 30 centimeters long. The flowers are yellow, small, 3 to 4

millimeters long, borne on erect and hairy panicles, which as often as long as the

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leaves. The fruit is a drupe, of varying shades of yellow, fleshy, oblong-ovoid,10 to

15 centimeters long, and slightly compressed, the skin is thin, and in the center is

a large flattened, fibrous seed, and when ripe, surrounded by an edible yellow pulp.

It is a widely cultivated tree for its fruit, with several varieties in cultivation.

The most popular are "carabao" and "piko," and the former used to be the preferred

export variety. The Guimaras mango is now considered the sweetest of mango

varieties produced in the Philippines.

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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. Are there any significant differences between the Positive Control and the

Experimental Group in treating alloxan-induced diabetic mice?

4. Are 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.

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 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 B-cells

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.

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Theoretical and Conceptual Framework

INPUT PROCESS OUTPUT

•Mango leaf extract •Confirmatory Test of •Present of Active

•Extract Concentration the physiological active Constituents such as
•50% of the Mango leaf constituent. Alkaloid, Phenolic
extract Compound, Flavonoids
•75% of the Mango leaf
extract
•100% of the Mango
leaf extract
•Normal Control •Positve for
•Healthy mice •Determination of Blood hypoglycemic activity
•Positive Control drugs Glucose Level in as shown by the
•Healthy mice will be Serum of Albino Mice significant lowering
administered Alloxan extracted in tail vein Fasting plasma
to make diabetic. •The Baseline Blood Glucose Level at
different time intervals
•Induced-diabetic mice Sugar Level (BSL) will
in Alloxan-induced
will be administered a be measured and
recorded after 15 diabetic mices.
dose of Metformin
(150mg/kg) mins, 30 mins, & 1
•Negative Control Drugs Hour.
•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)

Figure 2. This paradigm describes the hypoglycemic property or activity of the

Mangifera Indica Extract (MIE) applied to albino mice and the outcome of the test.

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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 constituent 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 Medicine, 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 Medicine Students in Gullas College of

Medicine.

Diabetic Patients: To raise awareness and knowledge on the health benefit of

using traditional medicine as an efficient and cost-effective complementary or

alternative way of controlling diabetes. Also, economically and geographically

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disadvantage patients can have an alternative way to control diabetes in a cost-

effective way which maximize the use of locally available resources.

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) and Pharmaceutical

companies to continue to innovate new medications that are produced with

readily available resources which are efficient and safe for general

consumptions.

Government and Department of Health: 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.

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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 L. the alloxan – induced

diabetic mice. This will be conducted at University of the Visayas Gullas College

of Medicine, Banilad, Mandaue City Cebu, Philippines in the first and second

semester of school year 2019-2020.

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.

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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

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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 non-sugar 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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