Investigation of anti-diabetic properties of Psidium guajava leaf in streptozocin induced diabetic rats.

Doctor of Philosophy in Biochemistry. University of KwaZulu-Natal, Westville 2015.Diabetes mellitus results in chronic hyperglycaemia, leading to defects in carbohydrate, fat and protein metabolism. Diabetes mellitus is also linked with elevated plasma cholesterol and triglyceride levels, which may promote the development of cardiovascular disease. Psidium guajava(PG) leaf is known to have a blood-glucose lowering effect in diabetic rats. The aim of this study was to carry out a phytochemical study of PG leaf extract; investigate its protective effect on pancreas and also its effect on muscle and liver glycogen synthase and phosphorylase activities in streptozotocin induced diabetic male Sprague-Dawley rats; Serum biomarkers of liver and muscle dysfunction such as alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) were also analyzed. The effect of PG on markers of lipid metabolism and on hormone sensitive lipase (HSL) enzyme was also investigated. A single dose of 40 mg/kg body weight of streptozotocin was administered to fasted male Sprague-Dawley rats intraperitoneally for diabetes induction. The aqueous extract of PG leaves was used to treat both normal and diabetic animals (400 mg/kg body weight) for 2 weeks while control animals were treated with the vehicle. After 2 weeks of treatment, PG was shown to enhance lowering of blood glucose in diabetic rats following a glucose load and protected pancreatic tissue from diabetic damage. GC-MS analysis of the aqueous extract of PG indicated the presence of phenolic compounds and triterpenes. In acute study, PG activated Protein kinase B(PKB/Akt) in skeletal muscle of streptozotocin induced diabetic rats. In the sub-chronic study, the treatment of rats with PG extract restored glycogen synthase activity depressed by diabetes and decreased glycogen phosphorylase activity in skeletal muscle. These changes in enzyme activity mirrored those in enzyme expression. It also restored glycogen synthase activity depressed by diabetes which was accompanied by reduced glycogen phosphorylase activity and increased glycogen levels in liver. PG decreased HSL activity in adipose tissue and liver and this was accompanied by reduced levels of serum triglycerides, total cholesterol, LDL-cholesterol, cardiac risk factor, atherogenesis and increased HDL-cholesterol. We conclude that PG has significant antidiabetic and hypolipidemic effects, and that these effects may be associated with the presence of triterpenes and phenolic compounds. PG increased GS activity, glycogen storage and reduced GP activity. It also reduced HSL activity and improved serum lipid profile