CHAPTER ONE
1.0 INTRODUCTION
1.1 BACKGROUND OF STUDY
Diabetes mellitus is the third leading cause of death, after heart attack and cancer. It is one of the most common endocrine dysfunction in the world resulting from a defect in insulin dynamics and has caused significant morbidity and mortality due to microvascular (retinopathy, neuropathy and nephropathy) and macrovascular (heart attack, stroke and peripheral vascular disease) complications with no known cure (Abdirahman et al.,2015; Patel et al.,2011). Diabetes mellitus affects millions of people worldwide and its prevalence increases and is projected to reach 500 million by the year 2030 (IDF, 2014). Reasons for this rise include increase in sedentary lifestyle, consumption of energy rich diet, obesity, higher life span, etc. (Yajnik, 2001). Regions with greatest potential are Asia and Africa; diabetes mellitus rates could rise to 2–3folds than the present rates (ADA, 1997). Diabetes mellitus (DM) is caused by the abnormality of carbohydrate metabolism which is linked to low blood insulin level or insensitivity of target organs to insulin (Maiti et al., 2004). Currently, available therapies for management of DM include insulin and various oral anti- diabetic agents such as sulfonylureas, biguanides, metformin, alpha-glucosidase inhibitors, thiazolidinediones and meglitinides. Despite considerable progress in the treatment of diabetes by oral hypoglycemic agents, search for newer drugs continues because the existing synthetic drugs have severe limitations (Maiti et al., 2004). Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. Treatment of illness and maintenance of health using herbal medicines is the oldest and most popular form of healthcare practice known
to humanity that has been practiced by all cultures in all ages throughout the history of civilization (Chikezie et al., 2015). WHO has recommended the evaluation of traditional plant treatments for diabetes because they are readily available, have low side effect and are considered to be excellent aspirants for oral therapy (Shokeen et al., 2008). In the developed countries, the rate of dependence on herbal medicine decreased based on the availability of synthetic drugs during the early part of the twentieth century. The resurgence of interest in anti-diabetic medicinal plant in developed countries is believed to be motivated by several factors that include: adverse reactions, high secondary failure rates and cost of conventional synthetic anti-diabetic remedies (Gurib-Fakim, 2006). Many herbal medicines have been recommended for the treatment of diabetes; the ethno- botanical information reports about 800 plants that may possess antidiabetic potential (Alarcon- Aguilara et al., 1998). Most antidiabetic plants belong to the family Leguminoseae, Curubitaceae, Liliaceae, Laminaceae, Asteraceae, Rosaceae, Euphorbiaceae, Moraceae, and Araliaceae (Saravanamuttu and Sudarsanam, 2012). The herbal drugs with antidiabetic activity are yet to be commercially formulated as modern medicines, even though they have been acclaimed for their therapeutic properties in the traditional systems of medicine (Wadkar et al., 2008). The biological effects of the plants or herbal products used as alternative medicines to treat diabetes are related to their chemical composition. Most of plants containing phytochemicals like glycosides, alkaloids, terpenoids, flavonoids, carotenoids, etc. are frequently implicated as having antidiabetic effect. Many of such plants known to be used primitively to alleviate symptoms of illnesses have been screened to have medicinal importance, some of which include:
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Azadirachta indica, Vernonia amygdalina, Allium sativum, Allium cepa, Ocimum gratissimum, Zingiber officinale, Momordica charantia, Carica papaya, Aloe vera, Ocimum sanctum (Udochukwu et al., 2015). Vernonia amygdalina is one of the most popular antidiabetic traditional herbal remedy in Nigeria (Gbolade, 2009). V. amygdalina, also known as ‘‘African bitter leaf’’, is a plant vegetable used for both food and traditional treatment of diseases that is, the leaves are macerated and used in cooking, while the extracts are used as tonic for prevention of certain illness (Farombi and owoeye, 2011). V. amygdalina is a valuable medicinal plant that is widespread in West Africa, it is known as bitter leaf due to its characteristic bitter taste and flavour, and can be used as an active anticancer, antibacterial, antimalarial, anti-diabetic and anti-parasitic agent (Udochukwu et al., 2015). V. amygdalina contains complex active components (phytochemicals) that are useful pharmacologically (Udochukwu et al., 2015). Phytochemicals are natural occurring bioactive compounds known for their health benefits. They are majorly responsible for the colour, flavour and aroma of fruits and notably vegetables (Kadiri and Olawoye, 2016). The phytochemical studies of V. amygdalina reveals the presence of saponins, flavonoids, alkaloids, terpenes, steroids, coumarins, phenolic acids, lignans, xanthones, anthraquinones, edotides and sesquiterpenes (Owoeye et al., 2010). Liver enzymes such as Aspartate amino transferase (AST), Alanine amino transferase (ALT), Gamma glutamyl transferase (GGT), and Alkaline phosphatase (ALP) is the most common laboratory test for the detection of liver disease and are regarded as liver marker enzymes. Elevation of liver marker enzymes is strongly related to obesity, diabetes and dyslipidemia, and
their measurement may act as a surrogate marker for determining the presence non-alcoholic fatty liver disease (NAFLD) (Angulo, 2002; Trombetta et al., 2005). Diabetes mellitus (DM) is associated with non-alcoholic fatty liver disease (NAFLD) including its severe form, non-alcoholic steatohepatitis (NASH) (Matteoni et al., 1999; Marchesini et al., 1999). Oral administration of the aqueous extract from V. amygdalina leaves could accelerate the reversion of liver damage through reduction of liver marker enzymes, including aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), glutamate- oxaloacetate amino transferase, glutamate pyruvate amino transferase, lactate dehydrogenase (LDH) and bilirubin indices in liver biochemical tests (Arhoghro et al., 2009; Iwalokun et al., 2006).
1.2 STATEMENT OF RESEAR CH PROBLEM
The research project is based on the effect of V. amygdalina (Bitter leaf) on diabetes mellitus as a result of the increase or decrease of the activities of the following enzymes; aspartate amino transferase (AST), alanine amino transferase (ALT), lactate dehydrogenase (LDH) and gamma glutamyl transferase (GGT) in blood serum.
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1.3 JUSTIFICATION OF STUDY
Studies in metabolism of biomolecules have established a relationship between carbohydrate and lipid metabolism which aids comprehension of the clinical significance; diabetes mellitus and non-alcoholic fatty liver disease (NAFLD). Diabetes Mellitus may be at higher risk for developing non-alcoholic fatty liver disease. There is need for future studies that would integrate more precise and proximal measures of liver health.
Increased level of liver enzymes like aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) characterize the non-alcoholic fatty liver disease (NAFLD), indicating hepatocellular injury (dysfunction) which could result to metabolic diseases and further leading to death. Adequate insight into the phytochemical properties and bio-molecular activities of V. amygdalina (Bitter leaf) and its interaction with the cells will give a better understanding in relation to its effects on Diabetes Mellitus.
1.4 AIM AND OBJECTIVES OF THE STUDY
The aim and objective of the study is: 1. To determine the phytochemical components of V. amygdalina (Bitter leaf) 2. To determine the bio-active compounds in the V. amygdalina (Bitter leaf) with GC-MS 3. To administer the methanol leaf extract and determine the effects of V. amygdalina on some plasma enzymes (AST, ALT, LDH and GGT) activities in streptozotocin induced diabetic rats.
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