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BIO00210 - INVIVO ANTIDIABETIC EFFECT OF DANIELLA OLIVERI ON GLUCOSE-6-PHOSPHATE AND GLYCATED HAEMOGLOBIN ON STREPTOZOTOZIN-NICOTINAMIDE INDUCED DIABETIC RATS


CHAPTER ONE

INTRODUCTION

  • Background to the study

In Nigeria, herbal therapies occupy a very special position in health delivery, especially among the rural populace. Easy accessibility and low cost of treatment enhance patronage. Diabetes mellitus is the commonest noncommunicable endocrine disease and is considered one of the leading causes of death all over the world; affecting over 100 million people worldwide. Many traditional plant treatments for diabetes mellitus are used throughout the world, and some of these plants have been scrutinized while a good number of them are yet to receive scientific scrutiny.

Diabetes happen as a result defects in the metabolism of carbohydrates to the lack of secretion of the pancreas to insulin, which leads to higher percentage of sugar in the blood and urine (Luo et al., 2004).Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications.Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, and damage to the eyes.

Natural plant and food sources provide α-amylase and α-glucosidase inhibitors, which plays a role in offering techniques to control hyperglycemia with minimum side effects (Chattopadhya, 1999).

Available drug regimens for the management of diabetes mellitus have certain disadvantages (Shenfield 2013) so there is need to develop newtherapies that can improve hyperglycaemicmanagement, but with reduced side effects.

 

  • Literature review

Medicinal plants are still an important source of novel pharmaceutical products and

natural products still remain as one of the best reservoir of novel structural-typed bioactive compounds. More than 25% of present medicine comes from natural products and an additional25% are structural alteration of the lead compounds from natural source. It is estimated that only15% of higher plants have been investigated for potentially useful biological activity.

In spite of the presence of known antidiabetic medicine in the pharmaceutical market, remedies from medicinal plants are used with success to treat this disease. Numerous traditional plant treatments for diabetes are used throughout the world. Plant drugs and herbal formulations are frequently considered to be less toxic and free from side effects than synthetic one (De la Estrella, 2010).Based on the WHO commendation, hypoglycemic agents of plant origin, used in traditional medicine are significant. The antihyperglycemic properties of these plants are due to their capability to reinstate the function of pancreatic tissues by causing a raise in insulin outputor decline in the intestinal absorption of glucose. Therefore, treatment with herbal drugs has an effect on protecting β cells and smoothing out fluctuation in glucose levels.

In general, there is very little biological knowledge on the specific modes of action in the treatment of diabetes, but most of the plants have been found to contain substances like phenolics, glycosides, alkaloids, terpenoids, flavonoids etc., that are normally concerned as having antidiabetic effects. Hence, in modern days, huge attention has been directed towards recognition of plants with antidiabetic ability that may be used effectively for human consumption.

There has been rapid development of different classes of antihyperglycemic drugs with distinctive pharmacological mechanism of action and, also, they have various toxicologicalprofiles. Numbers of medications are reported for the management of hyperglycemia like insulin,sulphonylureas, biguanides, thiazolidinedione, alpha-glucosidase inhibitors, glucagon-like peptide-1 analogues, glycosourics and dipeptidyl peptidase- IV inhibitors. Side effect ofantihyperglycemic drugs may cause agitation, altered behaviour, excess sweating, inaudible speech, tachycardia, seizures, and coma (Turner et al., 1996). Side effect of subcutaneous dose of insulin is relatedwith deep risk blurred vision and hypoglycemia. Sulfonylureas can cause hypoglycemia, whichstimulates appetite and leads to weight gain. Biguanides causes anorexia and encourage weightloss. Thiazolidinediones like pioglitazone, rosiglitazone can cause hepatic dysfunctioning as anadverse effect on regular treatment. Still there is a challenge to the medical system forManagement of diabetes without any side effects. However, natural remedies are widely used around the world to treat diabetes, but medical research does not support their effectiveness (Lou et al., 2004). So, the search for natural drugs from medicinal plants is being increased because of its fewer side effects, willingly availability and low cost. Thus the scientific validation of medicinal plants traditionally used in the treatment and management of diabetes is demanded.

Daniella oliveri(Rolfe) Fabiaceae commonlyknown as Ilorin balsam (eepoiya) or copaihu Africana leaves are used traditionally totreat diabetes and yellow fever . The leaveswere found to contain quercitrin, quercameritrin,rutin and the rare flavoured glycoside quercitin-3- methoxy 3-o rhamnosylpranosyl [7,8]- β- d-Glycopyranoside (Narssine) isolated from nbutanol extract.

 

  • Statement of the research problem

Diabetes mellitus was coined from Greek word, ‘diabetes’ meaning Siphon; to pass through and ‘mellitus’ meaning honeyed or sweet (Leonid, 2009). Diabetes mellitus is a metabolic disease, characterized by hyperglycemia together with impaired metabolism of glucose and other energy-yielding fuels, such as lipids and proteins(Scheen, 1997). This metabolic disorder is the result of a deficiency in insulin secretion or a resistance to insulin action, or both (Vinik and Vinik, 2003). More than 220 million people worldwide have diabetes and this number is likely to more than double by the year of 2030 (WHO, 2010).

Diabetes mellitus is characterized by hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, resulting from defects in insulin secretion or reduced sensitivity of the tissue to insulin (insulin resistance) and/or combination of both (Mishra et al., 2009). Several pathogenic processes are involved in the development of diabetes (Carpenter and Coustan, 1982). These range from autoimmune destruction of the cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action.

The basis of the abnormalities in carbohydrate, fat, and protein metabolismin diabetes is deficient action of insulin on target tissues (American Diabetes Association, 1997). Deficient insulin action results from inadequate insulin secretion and/or diminished tissue responses to insulin at one or more points in the complex pathways of hormone action (American Diabetes Association, 2004). Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia (O’sullivan and Mahan, 1964). Symptoms of marked hyperglycemia include polyuria, polydipsia, weight loss, sometimes with polyphagia, and blurred vision. Impairment of growth and susceptibility to certain infections may also accompany chronic hyperglycemia (O’sullivan and Mahan, 1964).

Acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis or the nonketotic hyperosmolar syndrome (American Diabetes Association, 2003). Long-term complications of diabetesinclude retinopathy with potential loss of vision; nephropathy leading to renal failure; peripheral neuropathy with risk of foot ulcers, amputations, and Charcot joints; and autonomic neuropathy causing gastrointestinal, genitourinary, and cardiovascular symptoms and sexual dysfunction. Patients with diabetes have an increased incidence of atherosclerotic cardiovascular, peripheral arterial, and cerebrovascular disease (American Diabetes Association, 2004). Hypertension and abnormalities of lipoprotein metabolism are often found in people with diabetes (American Diabetes Association, 2003).

The worldwide survey reported that the diabetes is affecting nearly 10% of the population (Kimet al., 2006 and Shah et al., 2006). It is the third leading cause of death (after heart disease and cancer) in many developed countries. It is a serious endocrine syndrome with poor metabolic control and responsible for increased risk of cardiovascular diseases including atherosclerosis, renal failure, blindness or diabetic cataract worldwide (Prasad etal., 2009).

 Therapeutic options for diabetes are diet, exercise, oral hypoglycemic drugs, and insulin therapy.Diabetic patients exhibit oxidative stress, which leads to lipid peroxidation and tissue damage including retinopathy, nephropathy, and coronary heart disease (Lyons and Wolffeet al., 1991). Dyslipidemia or hyperlipidemia is also involved in the development of cardiovascular complications, which are a major cause of morbidity and mortality (Reasner, 2008).