ABSTRACT

This study investigated the effects of crude extract and fractions from Napoleonae imperialis leaves on G-protein coupled receptors (GPCR), AMPKinase. cAMP, insulin, glucagon and some biochemical parameters in streptozotocin induced diabetic rats using acceptable chemical and biochemical methods. Guide extiact and active fractions from N. imperialis were subjected to gas chromatography mass spectrometry (GCMS) for identification of active compounds in the plant. In phase one, forty two male albino rats of mean weight 140 g were used for the study. The animals were placed into seven groups of six rats each. Group 1 (normal conti of), group 2 (diabetic control), group 3 (drug control), groups 4, 5 and 6 were the test groups administered 250, 500 and 1000 mg/kgbwt of the crude extract, gioup 7 received 500 mg/kgbwt ofthe extract only. There was significant (p < 0.05) decrease in cAMP, glucagon, blood glucose concentration, glycated hemoglobin, AST, ALT, ALP, bilirubin, albumin, total cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol levels, MDA, troponin, C-reactive proteins, nitric oxide, creatinine, urea, Na+, K+, Cl', HCOf in groups 3,4,5,6 7 when compared with group 2. There was significant (p < 0.05) increase in GPCR, insulin, AMPKinase, total protein, GSH, catalase, SOD, vitamin C and E, HDL-cholesterol, Hb, MCHC, MCH, PCV and MCV, RBC, WBC concentrations and body weight in groups 3,4,5,6,7 when compared with group 2. In phase two, a total of 54 animals of mean weight 140 g were placed into nine groups of six rats each. Group 1 (normal control), group 2 (diabetic control), group 3 (drug control), while groups 4-9 received fractions 1 - 6 respectively for 28 days. The results showed that fractions 2, 5 and 6 significantly reduced cAMP, glucagon, blood glucose concentration, glycated hemoglobin, AST, ALT, ALP, bilirubin, albumin, total cholesterol, triacylglycerol, LDL-cholesterol and VLDL-cholesterol levels, MDA, troponin, C-reactive proteins, nitric oxide, creatinine, urea, Na+, K+, Cl", HCO3’ when compared with group 2. There was significant (p < 0.05) increase in the GPCR, insulin, AMPKinase, total protein. GSH, CAT, SOD, vitamin C and E, HDL-cholesterol, Hb, MCHC, MCH, PCV and MCV, RBC, WBC and body weight in fractions 2, 5 and 6 when compared with group 2. Histopathological investigation of the liver, kidney and pancreas showed that the crude extract and fractions regenerated and restored the histoarchitecture of the organs and reduced the vacuolations ofLangerhans islets cell resulting in the absence of necrosis near to normal. GCMS analysis ofthe crude extract and fractions showed the presence ofmany bioactive compounds. Molecular docking revealed that Dibutyl phthalate, 7,9-ditert-butyl-l-oxaspiro (4,5) deca,6,9-diene,2,8-dione and Guaiol bound favourably to the target receptor involved in glucose metabolism with a binding score of-7.3 kcal/mol and -7.5 kcal/mol against PPAR-y. The findings of this study indicated that the crude extract and fractions of N. imperialis ameliorated the studied indicators of diabetes and its complications in STZ-induced diabetic rats. The possible synergistic action of the bioactive agents present in the leaves might be responsible for the effects.