Normoglycemic Rabbits Research Articles

Abstract 15480: Liraglutide Inhibits Atherosclerotic Plaque Progression in Rabbits Through the Downregulation of Multiple Inflammatory and Metabolic Pathways

Background: Liraglutide, a GLP-1- receptor agonists approved for the treatment of type 2 diabetes and obesity confers a lower CVD mortality. However, mechanisms underlying this finding remain unknown, particularly in normoglycemic subjects. We investigated the effects of liraglutide on the progression and pathobiology of atherosclerosis using multimodal intravascular imaging in rabbits. Methods: Rabbits atherosclerosis (N=16) were induced by balloon injury of the abdominal aorta and cholesterol feeding for 6 weeks. Then, rabbits were imaged with intravascular ultrasound (IVUS) and near-infrared fluorescence optical coherence tomography (NIRF-OCT) for the analysis of plaque burden and plaque inflammation (ProSense VM110 NIRF agent, 4 mg/kg/iv) respectively. Next, rabbits were randomized into: Control (n=8) or liraglutide (n=8, 0.1 mg/kg/day) groups. Imaging was repeated after 4 weeks, followed by histopathology and RNA analysis. On per-slice basis (every 0.4 mm) of IVUS imaging, the percent atheroma volume (PAV) was measured across the 40 mm balloon injured area. Atheroma progression was quantified as the ΔPAV between 6 and 10 weeks. Results: IVUS analyses (3200 slices/16 rabbits) revealed that liraglutide significantly reduced plaque progression (ΔPAV, 1.5% [0.2-2.8] vs. 9.3% [6.7-13.0] control, p=0.05). In vivo distance-corrected VM110 cathepsin inflammatory plaque activity was similar (ΔNIRF average plaque 25.2 [-9.8- 62] vs. 22.6 [3.9- 52.5] nM control, p=0.72). Plaques from liraglutide-treated animals however exhibited fewer RAM11+ macrophages (21.3±11.4 vs. control 30.9±16.7 macrophages/section, p=0.01) stry. Both plaques showed similar αSMA (45.2±6.7% vs 52.4±1.2% αSMA+ area/section, p=0.327). Liraglutide decreased inflammatory RNA transcripts (IL-6 and TNF-α), and RNA-seq transcriptomic analysis revealed that liraglutide altered inflammatory and metabolic pathways (as CRP, CYP3A6, Apo-A4 and FMO3). Blood glucose was normal and similar between groups (p>0.05). Conclusion: Liraglutide suppresses in vivo atherosclerotic plaque progression and plaque macrophage expression in normoglycemic rabbits. Further investigation of its plaque stabilizing effects in subjects with and without diabetes is warranted.

SCREENING THE INFLUENCE OF DILTIAZEM ON ORAL ANTIDIABETIC AGENTS IN EXPERIMENTAL ANIMALS

The main aim of this study was to assess the possibility of potential interaction of repaglinide and rosiglitazone with diltiazem. A calcium channel blocker, diltiazem potentially inhibits CYP3A4 and 2C8. Important to note, both drugs meglitinide and thiazolidinediones are actively metabolised by these isoenzymes. In the present study, various animal models like healthy rats, healthy rabbits and diabetic rats were used to assess possible interactions between the above said drugs. In normoglycemic rats, repaglinide induced hypoglycemia with onset at 1st h and duration was from 1st to 8th h, whereas in case of rosiglitazone, onset was at 2nd h and duration was up to 18 h. Normoglycemic animals pretreated with diltiazem had no effect on onset but duration of hypoglycemia induced by repaglinide was enhanced, whereas diltiazem caused early onset of hypoglycemia induced by rosiglitazone. In normoglycemic rabbits, hypoglycemia caused by repaglinide started at 1st h and continued upto 8th h, whereas rosiglitazone effect started at 4th h and continued upto 12th h. Diltiazem pre-treatment increased the duration of hypoglycemia caused by repaglinide. Diltiazem caused early onset and increase duration of hypoglycemia induced by rosiglitazone. After obtaining satisfactory results from the above two animal models, study was conducted on streptozotocin-induced diabetic rats. In diabetic rats, diltiazem has no hypoglycemic effect on group II animals. Repaglinide and rosiglitazone induced hypoglycemia from 1st h to 8th h and 2nd h to 18th h, respectively. Diltiazem pre-treatment had no effect on onset but significantly enhanced the peak and duration of hypoglycemia induced by repaglinide. Diltiazem pretreatment not only induced early onset but also enhanced peak and duration of hypoglycemia induced by rosiglitazone. Based on the results, it is concluded that the isoenzymes which are involved in the metabolism of repaglinide and rosiglitazone are sensitive to diltiazem and hence there is a need to go for therapeutic drug monitoring to readjust the dose and frequency of co-administration of these drugs.

SODIUM VALPROATE EFFECTS ON LIPID PROFILE AND GLUCOSE LEVEL IN NORMAL AND DIABETIC RABBITS

Background: Sodium valproate has turn out to be the most commonly prescribed antiepileptic drug (AED) worldwide. It is also prescribed to diabetic mellitus (DM) patient for treatment of neuropathic pain. Changes in lipid levels and lipid metabolism usually accompanied with diabetic disease leading to increases in circulating levels of free fatty acids (FFA), triglycerides and dense low-density lipoprotein together with reduced levels of high-density lipoprotein cholesterol levels. Objective: To investigate the effect of sodium valproate on lipid profile and glucose level and highlight these effects with and without diabetic disease. Methods: Thirty-two healthy, local domestic rabbits of both sexes were used in the present study. Animals were allocated into two main groups, group A and B. According to induction of diabetes both groups received the same food and put in the same environmental condition. blood glucose level and lipid profile has been done for all groups. Results: There was significant difference in the blood glucose level in the normoglycemic rabbits treated with sodium valproate (200 mg/kg) compared to the untreated (negative control group). The effect of valproate was also observed by the significant difference of blood glucose level in alloxan-induced diabetic rabbits treated with sodium valproate (200 mg) compared with the positive control group. Also, we have statistically observed the significant increase in total cholesterol (TC), low density lipoprotein – cholesterol (LDL-C), and triglyceride (TG) levels in normoglycemic rabbits treated with sodium valproate (200 mg/kg) compare to the negative control group, however, there is no significant difference regarding the high-density lipoprotein – cholesterol (HDL-C) level. As for the alloxan-induced diabetic rabbits, there was a statistically significant difference observed indicated an increase in level of TC, LDL-C, and TG and a decrease in HDL-C. Conclusion: The effect of sodium valproate on glucose level and lipid profile in diabetic rabbits could reflect a possible hypoglycemic and dyslipidemic effects which could be dangerous if the patient is on anti- diabetic drugs with or without cardiovascular accident, although it may be dose-dependent and still falls in the hypothesis field but further experimental studies on human are needed to explore this theory. Keywords: Sodium valproate, anticonvulsants, glucose, lipid Citation: Abdul Bari MA. Sodium valproate effects on lipid profile and glucose level in normal and diabetic rabbits. Iraqi JMS. 2018; 16(3): 247-257. doi: 10.22578/IJMS.16.3.4

English

In the present study, the ethanolic extract of Achyranthus aspera L. Leaves (EEA) were investigated for their pharmacognostic characteristics and hypoglycemic effects. The pharmacognosy of the plant was carried out using microscopic and macroscopic tools. Macroscopic studies revealed that the leaves were cauline, ramel, opposite, exstipulate, simple, sub-sessile, ovate, entire, acute, unicostate, reticulate, rough, coriaceous and hairy. The stem was erect, herbaceous, quadrangular, branched, solid, green and pubescent, while various internal parts were observed using powder drug for microscopic study. The hypoglycemic effect of the plant was studied in healthy normoglycemic rabbits. The EEA was tested in three doses (100, 150 and 200 mg/kg), and a dose dependent hypoglycemic effect was observed. The most significant hypoglycemic effect was observed against higher dose (200 mg/kg) which remained for 5 h while the hypoglycemic effect remained significant for 3 h against the lower dose. It was concluded that EEA has hypoglycemic properties and it is recommended for the treatment of diabetes mellitus II.   Key words: Pharmacognostic, hypoglycemic, Achyranthus aspera L.

Hypoglycemic effects of the aqueous extract of African Mistletoe, <em>Tapinanthus sesselifolius</em> (P. Beauv) van Tiegh (Loranthaceae)

The hypoglycemic effect of the aqueous extract of African mistletoe, Tapinanthus sesselifolius, was investigated in-vivo and in-vitro. Studies were carried out on normoglycemic and alloxan-induced hyperglycemic rabbits, and glucose uptake studies were done using the isolated intestine of normal rabbits. The safety studies (acute toxicity test) were carried out in mice. The results revealed that the aqueous extract of Tapinanthus sesselifolius exhibited transient reduction of blood glucose in normoglycemic rabbits and significantly lowered blood glucose level in hyperglycemic rabbits. The extract significantly decreased the level of glucose in serosal fluid dose dependently. The intraperitoneal (i.p.) LD50 of Tapinanthus sesselifolius was found to be 2000 – 2650 mg/kg within 95% confidence limits. The preliminary phytochemical screening showed positive test for biologically active substances such as saponins, tannins, flavonoids, terpenoids and glycosides. The data showed that Tapinanthus sesselifolius contain biologically active substances that may be useful in treatment of diabetes and thus gave a scientific basis for its use in herbal traditional medicine as an antidiabetic agent.Keywords: Phytomedicine, alloxan-induced hyperglycemia, glucose uptake

Antidiabetic properties of ethanolic fruit extract of <i>Solanium aethiopicum</i> L

The blood sugar lowering effect of the ethanolic fruit extract of Solanium aethiopicum L. (Solanaceae) was investigated on normoglycaemic and hyperglycaemic rabbits. The hypoglycaemic effect of Solanium aethiopicum L. was evaluated in alloxan-induced hypoglycaemia in rabbits at a dose of 80 mg/kg body weight. The evaluation was also done in normoglycaemic rabbits. The hypoglycaemic efficacy of the extract was compared to that of a standard drug, tolbutamide. The LD 50 was determined using mice. At a dose of 400 mg/kg body weight of the extracts, the fasting blood sugar (FBS) of normal rabbits was reduced by 49.1 % compared to that of tolbutamide 200 mg/kg body weight that caused a greater reduction of FBS by 73.3%. In alloxanized rabbits, blood sugar level was reduced by 37.0% and 54.2% by the extract and tolbutamide respectively. The LD50 of the extract in mice was calculated to be 2154.1±69.7 mg/kg. S. aethiopicum was found to be less potent when compared to tolbutamide in terms of their ability to reduce the blood sugar levels. Key words : Antidiabetic, ethanolic fruit extract, Solanium aethiopicum , hyperglycaemic, hypoglycaemic. Journal of Pharmaceutical and Allied Sciences Vol.2(2) 2004: 251-254

Hypoglycaemic effects of myrtle oil in normal and alloxan-diabetic rabbits

Myrtus communis L. (Myrtaceae) leaves as well as the volatile oil (Myrtii Oleum; MO) obtained from the leaves are used to lower the blood glucose level in type-2 diabetic patients in Turkish folk medicine. However, little attention has been paid to the therapeutic use of this plant. The present study was designed to investigate the oral hypoglycaemic activity of single and multiple doses of MO in normal and alloxan-diabetic rabbits. MO did not show any effect in normoglycaemic rabbits either in single or multiple dose administrations, but a good hypoglycaemic activity was observed 4 h after the administration to diabetic animals at 50 mg/kg. To investigate the effect of MO on repeated administration in both normal and diabetic rabbits, it was administered in 50 and 100 mg/kg doses once a day for one week. MO significantly lowered blood glucose by 51% in alloxan-diabetic rabbits on the fourth hour and the following days at a dose of 50 mg/kg ( P<0.001). The hypoglycaemic dose (50 mg/kg) was also determined by performing the oral glucose tolerance test (OGTT) in normal rabbits. The hypoglycaemic effect of the MO was 21% higher in rabbits, which received the glucose load orally, when compared with control group. However, MO did not affect serum insulin concentrations in normal and alloxan-diabetic rabbits but reduced the serum triglyceride concentrations by 14% in alloxan-diabetic rabbits. The above observations show that MO exerts hypoglycaemic as well as mild hypotriglyceridemic activity in diabetic animals. The reduction in blood glucose level may be due to the reversible inhibition of α-glucosidases present in the brush-border of the small intestinal mucosa, higher rate of glycolysis as envisaged by the higher activity of glucokinase, as one of the key enzymes of glycolysis, and enhanced rate of glycogenesis as evidenced by the higher amount of liver glycogen present after MO administration.

Lipid hydroperoxide induced corneal neovascularization in hyperglycemic rabbits

Purpose. To compare the effect of hyperglycemia on corneal neovascularization (NV) induced by linoleic acid hydroperoxide (LHP) in a rabbit model. Methods. Male New Zealand rabbits received 80mg/kg alloxan i.v. and subsequently developed hyperglycemia. Four weeks later, 10 µl of LHP (40mM) was injected into corneal stroma 5mm from the superior limbus with a 30 gauge needle. Vessel growth area from the limbal vasculature was measured over a period of 2 weeks and was correlated with plasma levels of insulin, HbA lc, and corneal vascular endothelial growth factor (VEGF). Results. Two days after alloxan, blood glucose was increased from 97 ± 4mg/dl in the untreated control group to 413 ± 3mg/dl. At 24 and 72 hours after LHP injection, VEGF in cornea of hyperglycemic rabbits was elevated 2 to 4 times above that of normoglycemic rabbits. At 14 days after LHP injection, the normoglycemic rabbits vessel growth area measured 2.42 ± 0.31mm², but in the hyperglycemic group, vessel growth area was significantly increased to 7.96 ± 2.26mm² (p < 0.05). At the end of the experimental period, HbA 1c was elevated from 3.9 ± 0.8 % to 8.4 ± 0.6 % and insulin was decreased from 440 ± 123.9pg/ml to 24 ± 11.0pg/ml. Conclusions. These data suggest that hyperglycemia may sensitize corneal and vascular endothelial cells, perhaps by glucose derived radicals, which enhance production of additional LHP through endogenous propagation reactions, and raise in turn the concentration of VEGF levels to induce an enhanced, sustained NV response.

Blood Sugar Lowering Effect of Anacardium occidentale Leaf Extract in Experimental Rabbit Model

Objective: The hypoglycaemic effect of A. occidentale aqueous leaf extract was evaluated on normoglycaemic and hyperglycaemic rabbits. Materials and methods: Antidiabetic activity of A. occidentale was evaluated using alloxan (80 mg/kg body weight, intraperitoneally) induced hyperglycemic rabbits. The potency of extract was compared with that of tolbutamide. The acute toxicity was determined using mice. Results: A dose 400 mg/ kg body weight of the extracts caused maximum lowering of blood sugar levels in both normal and alloxanized rabbits. The fasting blood sugar in the normoglycemic rabbits was reduced from 184.6 mg% to 74.2 mg% in three hours; while in alloxanized rabbits, blood sugar was reduced from 447.6 mg% to 242.8 mg% in three hours. The LD 50 of the extract in mice was 4000 mg/kg body weight when given intraperitoneally. Conclusion: A. occidentale is almost equipotent to tolbutamide in its ability to reduce the blood sugar levels. The above observation is consistent with the use of A. occidentale in foklore diabetes management.

The hypoglycaemic and antihyperglycaemic effect of Citrullus colocynthis fruit aqueous extract in normal and alloxan diabetic rabbits

Effects of the aqueous, glycosidic, alkaloidal and saponin extracts of the rind of Citrullus colocynthis on the plasma glucose levels were investigated in normal rabbits, while the effects of saponin extract on the fasting plasma glucose levels were studied in alloxan induced diabetic rabbits. In normal rabbits, oral administration of aqueous extract (300 mg/kg) produced significant reduction in plasma glucose after 1 h and highly significant after 2,3 and 6 h. Phytochemical screening revealed that the rind of C. colocynthis and its aqueous extract contains tertiary and quaternary alkaloids, glycoside and saponin components. The hypoglycaemic effects of these components given orally at a dose (50 mg/kg) were studied in normoglycaemic rabbits. Result showed that the alkaloidal extract did not significantly lower the blood glucose levels from 132 mg/100 ml at 0 h to 120 mg/100 ml after 6 h, while the glycosidic extract significantly lowered the fasting glucose levels after 2 and 3 h and highly significant after 6 h. The effect was more pronounced with saponin extract, the saponin significantly lowered the fasting glucose levels after 1 and 2 h and higly significant ( P<0.001) after 3 and 6 h. Graded doses (10, 15 and 20 mg/kg) of saponin extract, when given orally to alloxan diabetic rabbits, produced a significant reduction of plasma glucose concentration. These results suggest that the aqueous extract of the rind of C. colocynthis possesses a hypoglycaemic effect and its hypoglycaemic action could be attributed for more extent to the presence of saponin in addition to the presence of glycosidic components.

Effects of Hyperglycemia on Small Cerebral Infarctions in Awake Rabbits

This study concerns the effects of hyperglycemia on small infarctions in the rabbit brain. Small ischemic foci were produced in both normoglycemic (6 mM) and hyperglycemic (25 mM) rabbits, by injecting small plastic beads into the left heart ventricle under short-acting anaesthesia. 2-deoxy-D-[14C]glucose (2-DG) autoradiography was used to trace ischemic regions in which glucose uptake was increased, either shortly after, or six hours after, the embolization (in awake rabbits). A lesion was characterized by a 2-DG activity > 120%. The obtained freeze-dried sections were inspected for infarcts (with lost tissue structure and increased transparency to light).In the short experiments (< 1 hour), lesions could be detected throughout the brains, indicating hypoxic regions with enhanced glycolysis. In some foci, mostly located in the basal ganglia (the region containing the largest lesions), a central dip could be seen in the 2-DG accumulation, suggesting a poor glucose supply to the ischemic core. The lesions in the basal ganglia of rabbits that were made hyperglycemic were smaller and did not show such dips. No infarcts could be found in the tissue sections.In the long experiments (6 hours), both infarcts and lesions could be found. The impact of hyperglycemia on the infarction process in different brain regions was evaluated by measuring the infarct volumes, and by evaluating the fraction of infarcts - number of infarcts found in freeze-dried sections/number of foci (both lesions and infarcts) found in the 2-DG autoradiograms. Hyperglycemia reduced the fraction of infarcts in the cortex, and reduced the size of infarcted areas in the brain stem. In summary, this study shows that the impact of hyperglycemia on the ischemic outcome depends on where in the brain the ischemic focus is located. This adds interesting information as to what is known about the general effects of glucose on cerebral ischemia.

Antihyperglycemic Effect of Fresh Opuntia dillenii Fruit from Tenerife (Canary Islands)

The fresh fruit of Opuntia dillenii (Ker-Gawl.) Haw. is used as an antidiabetic agent in Canary Islands folk medicine. To determine whether or not there is a scientific basis for this popular use, the effects of the fruit's red palatable juice on blood glucose levels were assessed in normoglycemic and alloxan-induced diabetic rabbits. Single, or repeated (once a day for 7 consecutive days) oral doses (5 ml/kg) of the juice did not alter blood glucose levels in either normoglycemic or alloxan-induced diabetic rabbits. Instead, a single oral dose reduced significantly the percent increase of glucose-induced hyperglycemia in both normoglycemic and alloxan-induced diabetic rabbits. In normoglycemic rabbits, the hypoglycemic effect of the juice was comparable to that of an oral dose of tolbutamide (100 mg/kg) under the same oral glucose-tolerance conditions; however, the juice did not increase glucose-induced plasma insulin levels. Moreover, the antihyperglycemic effect of the drug was not detected when rabbit...

Baroreflex dysfunction in diabetes mellitus. II. Site of baroreflex impairment in diabetic rabbits.

In our companion paper [T. S. McDowell, M. W. Chapleau, G. Hajduczok, and F. M. Abboud, Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H235-H243, 1994] we report that baroreflex-mediated bradycardia is impaired in diabetic rabbits. The purpose of the present study was to identify the site of impairment. Diabetes was induced in rabbits by alloxan (90-100 mg/kg iv; n = 7). Alloxan-treated rabbits that remained normoglycemic (n = 8) and rabbits given saline instead of alloxan (n = 4) served as controls. Twenty-four weeks after administration of alloxan or saline, rabbits were anesthetized with alpha-chloralose. Aortic baroreceptor and renal sympathetic nerve activity (RSNA) were recorded during phenylephrine- and nitroglycerin-induced changes in arterial pressure. The slope of the baroreceptor pressure-activity relation was not significantly different in diabetic rabbits (1.3 +/- 0.3%/mmHg, n = 7) compared with either alloxan-treated (1.3 +/- 0.1%/mmHg) or saline-treated normoglycemic rabbits (1.2 +/- 0.2%/mmHg). The slope of the arterial pressure-RSNA relation was not significantly different in diabetic rabbits (-3.5 +/- 0.3%/mmHg, n = 7) compared with the alloxan-treated normoglycemic rabbits (-3.0 +/- 0.4%/mmHg, n = 8) and was greater than that in saline-treated normoglycemic rabbits (-1.9 +/- 0.3%/mmHg, n = 4; P < 0.05). The decreases in heart rate in response to electrical stimulation (10 V, 2 ms, 0.5-16 Hz) of the cut peripheral end of the right cervical vagus were similar in diabetic and alloxan-treated normoglycemic rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Baroreflex dysfunction in diabetes mellitus. I. Selective impairment of parasympathetic control of heart rate.

The purpose of this study was to determine the effect of diabetes mellitus on baroreflex control of heart rate. Diabetes (blood glucose = 378 +/- 21 mg/dl) was induced in rabbits by alloxan (n = 9). Alloxan-treated rabbits that remained normoglycemic (n = 9) and rabbits given saline instead of alloxan (n = 5) served as controls. Baroreflex control of heart rate was evaluated in conscious rabbits by measuring changes in heart rate during phenylephrine-induced increases and nitroglycerin-induced decreases in arterial pressure. In diabetic rabbits, the gain of the baroreflex-mediated bradycardia in response to increased pressure decreased significantly from -1.8 +/- 0.3 beats.min-1 x mmHg-1 before alloxan (n = 9) to -0.9 +/- 0.1 and -0.9 +/- 0.3 beats.min-1 x mmHg-1 after 12 and 24 wk of diabetes, respectively (n = 8; P < 0.05). There was no significant change in baroreflex gain in either alloxan-treated or saline-treated normoglycemic rabbits. Baroreflex-mediated bradycardia was not influenced significantly after beta-adrenergic blockade with propranolol (1 mg/kg) and was still impaired in diabetic vs. control rabbits after propranolol. The gain of the baroreflex-mediated tachycardia in response to decreased pressure was not altered in any of the three groups. Propranolol significantly decreased but did not abolish baroreflex-mediated tachycardia. Neither the vagal nor the sympathetic component of the tachycardia was altered significantly by diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood sugar lowering effect of Vernonia amygdalina Del, in an experimental rabbit model

AbstractThe aqueous leaf extract of Vernonia amygdalina, Del, (Compositae) given i.p. produced a dose‐related fall in blood sugar. A dose of 80 mg/kg body weight of adult rabbit produced a maximum lowering of blood sugar in both fasted normal and alloxanized rabbits. The fasting blood sugar in normoglycaemic rabbits was reduced from 96 mg% to 48 mg% in 4 h. In alloxanized rabbits, the blood sugar was reduced from the mean value of 520 mg% to 300 mg% in 8 h. The hypoglycaemic effects were compared with those of tolbutamide. Acute toxicity studies of the extract in mice gave LD50 value of 1122 mg/kg body weight when given i.p. The blood sugar lowering effect of Vernonia amygdalina extract may involve a mechanism not related to insulin secretion.

Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus

Salvia fruticosa Mill. has a folk reputation in the eastern Mediterranean region as a hypoglycémie agent. In order to confirm this claim, a 10% infusion of its leaves was tested, at an oral dose of 0.250 g kg b.wt., on normoglycemic rabbits and in rabbits made hyperglycemic by alloxan administration. This oral dose caused a statistically significant reduction in blood glucose levels in alloxan-hyperglycemic rabbits, but not in normoglycemic animals, only after repeated administrations of the infusion (once a day for 7 consecutive days). Instead, the hypoglycemic effect was evoked by single oral doses of infusion in both normoglycemic and alloxan-hyperglycemic rabbits orally loaded with glucose. However, in these animals S. fruticosa infusion did not modify plasma insulin levels. Moreover, the hypoglycemic effect of the drug was not evoked in rabbits which received the glucose load intravenously. These data strongly suggest that S. fruticosa treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose.

Hypoglycaemic Activity of Dioscoretine from Tubers ofDioscorea dumetorumin Normal and Alloxan Diabetic Rabbits

Dioscoretine isolated from the aqueous fraction of the methanol extract of Dioscorea dumetorum tubers when administered intra-peritoneally to normal and alloxan diabetic rabbits produces significant hypoglycaemic effects at a dose of 20 mg/kg. The fasting blood sugar in normoglycaemic rabbits was reduced from 112 mg/100 ml to 55 mg/100 ml after 4 hours. In alloxan diabetic rabbits, the blood sugar was lowered from 520 mg/100 ml to 286 mg/100 ml at the same time interval. The aqueous fraction of the methanol extract produced comparable effects at 100 mg/kg. The chloroform fraction of the same extract raised the fasting blood sugar of normal rabbits to 196 mg/100 ml after 6 h. The acute toxicity studies gave LD50 values of 1.4 g/kg for the aqueous fraction and 0.58 g/kg for dioscoretine when tested on mice. The hypoglycaemic effects were compared to those of tolbutamide.

Antidiabetic and aldose reductase activities of biflavanones of Garcinia kola

Kolaviron, a mixture of C-3/C-8 linked biflavonoids obtained from Garcinia kola produces significant hypoglycaemic effects when administered intraperitoneally to normal and alloxan diabetic rabbits at a dose of 100 mg kg-1. The fasting blood sugar in normoglycaemic rabbits was reduced from 115 mg/100 mL to 65 mg/100 mL after 4 h. In alloxan diabetic rabbits, the blood sugar was lowered from 506 mg/100 mL to 285 mg/100 mL at 12 h. The hypoglycaemic effects have been compared with those of tolbutamide. Kolaviron inhibited rat lens aldose reductase (RLAR) activity, with an IC50 value of 5.4 x 10(-6). The significance of these findings in the potential use of kolaviron as an antidiabetic agent is discussed.

Hypoglycaemic activity of Anthocleista vogelii (Planch) aqueous extract in rodents

AbstractThe hypoglycaemic effect of Anthocleista vogelii was studied in mice, rats and rabbits. Aqueous extract of the plant obtained by infusion from finely pulverized root was used. The extract (100, 400 and 800 mg/kg) induced significant hypoglycaemic activity in a dose‐related fashion at 2 h after oral administration in mice and rats with ED25 of 250 mg/kg and 350 mg/kg respectively. The extract (800 mg/kg, orally) similarly induced statistically significant lowering of blood glucose levels at 8 h in normoglycaemic rabbits. The extract (400 mg/kg and 800 mg/kg, orally) also caused reduction of blood glucose levels in alloxan‐induced diabetic animals. The results of this study indicate that the aqueous extract of the roots of Anthocleista vogelii possess favourable hypoglycaemic activity both in normo and hyperglycaemic animals compared to chlorpropamide as a standard.

Repair of the corneal epithelial adhesion structures following keratectomy wounds in diabetic rabbits

In corneal tissue from a diabetic patient 15 months after delayed epithelial healing following vitrectomy surgery, electron microscopy revealed a discontinuous basement membrane; immunohistochemically, fibronectin was present in the basement membrane zone. To determine whether alterations in repair of the basement membrane, anchoring fibrils and hemidesmosomes occur in wounds in diabetics, we studied the pattern of histochemical localization of bullous pemphigoid antigen (the intracellular hemidesmosome plaque component), laminin and type VII collagen (the anchoring fibril collagen) in alloxan-induced diabetic rabbits following superficial keratectomy. Ultrastructural studies of basal laminae and hemidesmosomes also were performed. Epithelial wound closure was complete by 66-72 h after 7-mm superficial keratectomies. Type VII collagen localized at the base of the epithelium at the wound periphery by 66 h, appearing as a beaded line underlying the epithelium; at 1 week, as in control rabbits, the localization zone extended across the wound bed. Polyclonal antibodies to laminin and bullous pemphigoid antigen showed similar localization. Small segments of basal laminae were noted by electron microscopy of the wound periphery as early as 66 h post-keratectomy. By 2 weeks, an increase in hemidesmonsomes associated with segments of discontinuous basal lamina was apparent. No obvious differences in the time or pattern of re-appearance of the adhesion complex in keratectomy wounds could be discerned between normoglycemic and hyperglycemic rabbits. Thus, healing defects in diabetics may be due to factors other than reassembly of adhesion structures.