Project Materials

EFFECTS OF ETHANOL, METHANOL AND N-HEXANE LEAF AND FRUIT EXTRACTS OF Kigelia africana ON SOME OXIDATIVE AND BIOCHEMICAL PARAMETERS IN ALLOXAN-INDUCED DIABETIC RATS

ABSTRACT

The International Diabetes Federation (IDF) estimates that the global incidence of diabetes will reach 350 million by 2030. Kigelia africana is widely utilised for ethnomedicinal purposes, despite a scarcity of scientific information on its application. The purpose of this study was to assess the plant’s anti-diabetic and antioxidant properties. The investigation was conducted using ethanol, methanol, and n-hexane extracts of Kigelia Africana leaves. Alloxan diabetes was produced in 60 mature male albino rats weighing 90–160 g. Alloxan was dissolved in cold normal saline. After 72 hours, diabetes was established, and the rats were separated into twelve (12) groups of five (5) each. Group 1 served as the normal control, group 2 was the diabetic untreated, group 3 received 2.5 mg/kg b.wt of glibenclamide, groups 4, 6, and 8 received ethanol, methanol, and n-hexane leaves extracts, and groups 5, 7, and 9 received ethanol, methanol, and n-hexane fruit extracts at 500 mg/kg b.wt. Groups 10-12 received an equal combination of leaf and fruit extracts. The rats were fed orally for 21 days before being statistically evaluated for biochemical and oxidative markers. Standard phytochemical screening for diverse bioactive chemicals revealed the presence of flavonoids, alkaloids, saponins, soluble carbohydrates, tannin, steroids, glycosides, and reducing sugars. Proximate analysis revealed the presence of proteins (13.9%), carbs (63.5%), lipids and oils (11.4%), and crude fibre (2.2%). The LD50 values indicated that the extracts were safe.

Chapter one

INTRODUCTION

Diabetes mellitus is a metabolic condition caused by a deficiency in insulin secretion, insulin action, or both. Insulin insufficiency causes chronic hyperglycemia and abnormalities in carbohydrate, lipid, and protein metabolism (Kumar et al., 2011). During diabetes, the failure of insulin-stimulated glucose absorption by fat and muscle keeps blood glucose levels high, increasing glucose uptake by insulin-independent tissue.

Increased glucose flux enhances oxidant production while impairing antioxidant defences via multiple interacting non-enzymatic, enzymatic, and mitochondrial pathways (Klotz 2002; Mehta et al. 2006).

These include activation of protein kinase C isoforms (Inoguchi et al., 2000), increased hexosamine pathway (Kaneto et al., 2001), glucose autoxidation (Brownlee, 2001), increased methylglyoxal and advanced glycation end-product (AGE) formation (Thornalley, 1998), and increased polyol pathway flux (Lee and Chung, 1999).

These seemingly distinct mechanisms are the outcome of a similar process: superoxide overproduction by the mitochondrial electron transport system (Tushuizen et al., 2005).

This hyperglycemic-induced oxidative stress eventually results in modification of intracellular proteins resulting in an altered function and DNA damage, activation of the cellular transcription (NFK B), causing abnormal changes in gene expression, decreased production of nitric oxide, and increased expression of cytokines, growth factors, and pro-coagulant and pro-inflammatory molecules (Palmer et al., 1988; Evans et al., 2002; Klotz, 2002; Taniyama and Griendling, 2003

Oxidative stress causes molecular and cellular tissue damage in a wide range of human disorders (Halliwell, 1994), including diabetes mellitus.

Diabetes alters lipid profiles, particularly an increased sensitivity to lipid peroxidation (Lyons, 1991), which contributes to an increased incidence of atherosclerosis (Guigliano et al., 1996), a prominent consequence of diabetes mellitus.

These patients exhibit increased oxidative stress, as seen by increased free radical generation, lipid peroxidation, and decreased antioxidant status (Baynes, 1991).