ANTIHYPERGLYCEMIC AND ANTIHYPERLIPIDAEMIC EFFECTS OF EXTRACTS AND FRACTIONS OF CLEOME RUTIDOSPERMA DC AND SENECIO BIAFRAE (OLIV. & HIERN) IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
ANTIHYPERGLYCEMIC AND ANTIHYPERLIPIDAEMIC EFFECTS OF EXTRACTS AND FRACTIONS OF CLEOME RUTIDOSPERMA DC AND SENECIO BIAFRAE (OLIV. & HIERN) IN STREPTOZOTOCIN-INDUCED DIABETIC RATS
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Date
2015-01
Authors
OKORO, ISRAEL OGHENEVWODOKOHWO
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Abstract
The antihyperglycemic and antihyperlipidaemic effects of leaves of Cleome rutidosperma and roots of Senecio biafrae were investigated in streptozotocin (STZ)- induced diabetic mice and rats. Both short term and long term effects of four different solvent extracts (petroleum ether, acetone, ethanol and water extracts) of both plants were evaluated. Single administration of the extracts at a dose of 500 mg/kg body weight was done for the first phase of the study (acute study) while graded daily doses (125 mg/Kg, 250 mg/Kg and 500 mg/Kg) were administered orally to diabetic rats in the second phase of the study (long term, 28 days). To further evaluate the antidiabetic activity of the most active extract (aqueous) of both plants, a bioassay guided fractionation of this crude extract was carried out. Fractions of both plants were tested in different prandial states; fasting, postprandial and post glucose loaded. All the extracts as well as the standard drug, glibenclamide (at 600 μg/kg body weight) significantly (p< 0.05) lowered blood glucose level of the diabetic mice and rats for both phases. The effect was highest with the aqueous extracts of both plants. The oral median lethal dose (LD50) of the extracts in rats was > 5000 mg/kg body weight. The aqueous extract of both plants at different doses administered for 28 days, produced significant (p < 0.05) changes in the diabetes indices evaluated; there was significant (p<0.05) decrease in the level of fasting blood glucose, feed and water intake as well as serum cholesterol, triacylglycerols, low density lipoprotein (LDL), creatinine, urea, bilirubin and activities of liver marker enzymes (AST, ALT and ALP). Significant (p < 0.05) increases occured in body weight, High density lipoprotein (HDL), and activities of Superoxide dismutase (SOD), Catalase (CAT), Glutathione-S-Transferase (GST) and Glutathione Reductase (GR). The aqueous extracts of both plants stimulated hepatic glucokinase activity and inhibited the gluconeogenic enzyme, glucose-6-phosphatase.
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Fractions of both plants produced significant reduction of blood glucose level at different prandial states. Fractions of both plants at doses of 125 and 62.5 mg/kg b.w., significantly (p<0.05) reduced postprandial hyperglycemia after 6 hour of administration. Likewise, glucose tolerance activity was significantly (p<0.05) improved in the presence of fractions of the plants to varying extent. Therefore, the results suggests that the plant possess antidiabetic and antilipidaemic properties mediated through: (a) Reduction of postprandial hyperglycemia and improvement of glucose tolerance activity and (b) Inhibition of glucose 6-phosphatase resulting in reduction of hepatic gluconeogenesis and glycogenolysis. C. rutidosperma and S. biafrae hold promise for development as new and safe oral antidiabetic agents for the management of diabetes mellitus.
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A DISSERTATION SUBMITTED TO THE SCHOOL POSTGRADUATE STUDIES, AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA.
IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR AWARD
OF A
DOCTOR OF PHILOSOPHY IN BIOCHEMISTRY
DEPARTMENT OF BIOCHEMISTRY
FACULTY OF SCIENCE
AHMADU BELLO UNIVERSITY, ZARIA, NIGERIA.
Keywords
ANTIHYPERGLYCEMIC,, ANTIHYPERLIPIDAEMIC EFFECTS,, EXTRACTS,, FRACTIONS,, CLEOME RUTIDOSPERMA DC,, SENECIO BIAFRAE,, (OLIV. & HIERN),, STREPTOZOTOCIN-INDUCED,, DIABETIC RATS,