Effects of Ficus exasperata vahl. (moraceae) leaf aqueous extract on the renal function of streptozotocin-treated rats.

The present study was undertaken to evaluate the possible reno-protective effect of Ficus exasperata leaf aqueous extract (FEE) in a rat experimental paradigm of diabetes mellitus. Forty Wistar rats (weighing 200-230 g) were divided into four (A, B, C, and D) groups, each group consisting of 10 rats. Group A rats served as 'control' animals and received citrate buffer (pH 6.3) solution in quantities equivalent to intraperitoneally-administered volumes of streptozotocin (STZ) and FEE. Diabetes mellitus was induced in Groups B and C rats by intraperitoneal injections of STZ (75 mg/kg). Group C rats were additionally treated with FEE (100 mg/kg/day, p.o.) 4 weeks post STZ injections, for 4 consecutive weeks. Group D rats received FEE (100 mg/kg/day p.o.) only for 4 weeks. Post-euthanisation, kidney tissues were excised for histopathological evaluation and processed for light microscopy. Plasma malondialdehyde and tissue nitric oxide were determined. Serum creatinine, blood urea nitrogen, nitrite, and albumin concentrations were measured for the evaluation of renal function. The diabetic rats significantly lost more weight and their blood glucose levels were significantly elevated as compared to the 'control' group of animals. Renal dysfunction was evidenced by kidney hypertrophy, decreased renal blood flow, and increased serum creatinine and nitrite concentrations. Furthermore, vascular dysfunction, as evidenced by decreased carotid blood flow, was observed in the diabetic rats. FEE treatment positively ameliorated the alterations in the biochemical variables in the STZ + FEE-treated rats. In conclusion, our findings suggest that FEE treatment ameliorates STZ-induced nephrotoxicity.

Insulin-induced immunohistochemical and morphological changes in pancreatic beta-cells of streptozotocin-treated diabetic rats.

This study was undertaken to investigate insulin-induced changes in the immunohistochemistry and morphometry of pancreatic beta-cells, plasma insulin and blood glucose concentrations of streptozotocin (STZ)-treated diabetic rats. Fifty male Wistar rats (200-250 g) were randomly divided into three experimental groups (viz., A: control group, B: STZ-treated group, and C: STZ+insulin-treated group). Diabetes was induced in group B and group C rats by single intraperitoneal injections of STZ (75 mg/kg body weight), while each animal in the "control" group A received equal volume of citrate buffer solution (pH 6.3) intraperitoneally. STZ+insulin-treated group C diabetic rats were additionally treated with subcutaneous injections of lente insulin (0.5 U/kg body weight) daily from Day 10 to Day 30 of our 40-day study period. The rats used were sacrificed at different time intervals (10th, 20th, 30th and up to the 40th day) following STZ treatment. Fragments of endocrine pancreas of each rat were randomly processed for immunohistochemistry staining and pancreatic insulin content. In diabetic state, pancreatic beta-cells showed a weak immunostaining for insulin on Day 10. Thereafter, insulin administration (in the group C rats) caused a significant decrease (p < 0.05) in the elevated blood glucose levels, and a significant increase (p < 0.05) in the serum insulin concentrations. The surviving beta-cells regenerated and virtually regained their normal immunostaining and functional status for insulin. On the 30th day, the pancreatic insulin contents of the insulin-treated group C rats showed approximately 45-fold increase in immunoreactivity when compared with the immunoreactivity of the same STZ+insulin-treated rats on Day 10 of the 40-day study period. The present study illustrates the sequence of morphological changes that occur in the islets of Langerhans following STZ administration and subsequent insulin treatment. The study also suggests that administration of a moderate single dose of STZ in Wistar rats produces specific necrosis of beta-cells, typical of type 1 insulin-dependent diabetes. The experimental evidence obtained in this study appears to suggest that induction of regenerative stimulus (by insulin treatment) in diabetic state triggers pancreatic regenerative processes, thereby restoring functional activities of the pancreas.

Hyperglycaemic effect of Artocarpus communis Forst (Moraceae) root bark aqueous extract in Wistar rats.

Decoctions and infusions of Artocarpus communis (Forst) (family: Moraceae) root bark are traditionally used among the Yoruba-speaking people of western Nigeria as folk remedies for the management, control and treatment of an array of human diseases, including type 2 diabetes mellitus. Although numerous bioactive prenylflavonoids have been isolated from the roots, stem bark and leaves of A communis, to the best of our knowledge, the effects of the plant's root bark extract on animal models of diabetes mellitus have hitherto not been reported in the biomedical literature. In our pilot study, we observed that A communis root bark aqueous extract (ACE) raised blood glucose concentrations in rats. In view of this finding, the present study was undertaken to investigate the glycaemic effect of ACE in comparison with that of streptozotocin (STZ) in Wistar rats. Four groups (A, B, C and D) of Wistar rats, each group consisting of 10 rats, were used in this study. Group A rats received distilled water in quantities equivalent to the volume of ACE administered. Diabetes mellitus was induced in the animals in groups B and C by intraperitoneal (ip) injections of STZ (75 mg/kg body weight). The rats in group C were additionally treated with ACE (50 mg/kg body weight ip) from the third to the tenth day following STZ treatment. Group D rats received ACE (12.5-100 mg/kg body weight ip) only. The effects of ACE were compared with those of STZ on blood glucose concentrations, serum and pancreatic insulin levels, hepatic hexokinase (HXK) and glucokinase (GCK) activities, and hepatic glycogen contents in the experimental animal paradigm used. The rats in treated groups B, C and D exhibited pronounced polyuria, hypo-insulinaemia and hyperglycaemia. Group D rats developed significant hyperglycaemia (p < 0.05) immediately after ACE administration, whereas groups B and C rats became hyperglycaemic 24 to 72 hours post STZ and STZ + ACE treatments, when compared with the control group A rats. Hepatic glycogen contents significantly increased (p < 0.05), while HXK and GCK activities significantly decreased (p < 0.05) in the treated groups B, C and D rats, when compared with the control group A rats. The findings of this laboratory animal study indicate that A communis root bark aqueous extract induced acute hyperglycaemia in Wistar rats, and that it disrupted the biochemical variables of the rat pancreas and liver.

Hypoglycaemic and hypotensive effects of Globimetula cupulata (DC) Van Tieghem (Loranthaceae) aqueous leaf extract in rats.

The leaves of some mistletoes, specifically Loranthus micranthus Linn, Tapinanthus dodoneifolius (DC) Danser and Globimetula cupulata (DC) Van Tieghem (family: Loranthaceae), are used traditionally in Nigerian folk medicine to manage, control and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the folkloric, ethnomedical uses of Globimetula species, the present study was undertaken to investigate the hypoglycaemic and hypotensive effects of Globimetula cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) in rat experimental paradigms. The hypoglycaemic effect of the plant extract was examined in normal (normoglycaemic) and diabetic (hyperglycaemic) rats using a streptozotocin (STZ)-induced diabetes model. Normotensive Wistar and hypertensive Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant extract. Metformin (MFM, 500 mg/kg po) was used as the reference hypoglycaemic agent for comparison. Acute oral administrations of G cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal and STZ-treated diabetic rats. Furthermore, acute intravenous administrations of GCE (50-800 mg/kg iv) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressure and heart rates of the normotensive and hypertensive rats used. Although the exact hypoglycaemic and hypotensive mechanisms of action of the plant extract still remain speculative, it is unlikely that the extract induced hypotension in the mammalian experimental animal model via cholinergic mechanisms, since its cardiovascular effects were resistant to atropine pretreatment. However, the findings of this experimental study indicated that Globimetula cupulata aqueous leaf extract possesses hypoglycaemic and hypotensive properties. This therefore lends pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/ or control of diabetes mellitus and hypertension among the Yoruba-speaking people of western Nigeria.