Antihyperglycemic action of angiotensin II receptor antagonist,valsartan, in streptozotocin-induced diabetic rats

OBJECTIVES: In the present study, we use valsartan, a highly selective antagonist for angiotensin(1) (AT(1)) receptor subtype, to investigate the effect of AT(1) receptor on the plasma glucose metabolism in streptozotocin-induced diabetic rats (STZ-diabetic rats). METHODS: The plasma glucose concentration was assessed by glucose oxidase method and plasma insulin was measured using enzyme-linked immunosorbent assay. Systolic blood pressure (SBP) was determined by the tail-cuff method. The intravenous glucose challenge test (IVGCT) was carried out to evaluate the effect of valsartan on the glucose utilization in vivo. The mRNA levels of the subtype 4 form of glucose transporter (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver were detected by Northern blotting analysis. Moreover, the protein levels of GLUT4 in isolated soleus muscle and hepatic PEPCK were investigated using Western blotting analysis. RESULTS: A single intravenous injection of valsartan decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Plasma glucose-lowering action of valsartan also observed in normal rats although in a way not so effective as that in STZ-diabetic rats. Valsartan at the dose of 0.2 mg/kg that produced the maximal plasma glucose-lowering activity in STZ-diabetic rats is also effective to lower the SBP. However, oral treatment with nifedipine or nicorandil in STZ-diabetic rats at the dose sufficient to decrease SBP showed no change of plasma glucose. Otherwise, infusion of saralasin (10 microg/kg per min) into STZ-diabetic rats produced a plasma glucose-lowering activity similar to that by valsartan at 0.2 mg/kg. Moreover, valsartan (0.2 mg/kg) significantly attenuated the raise of plasma glucose induced by IVGCT in normal rats. Repeated intravenous administration of valsartan (0.2 mg/kg) in STZ-diabetic rats resulted in the lowering of plasma glucose after 3 days. The mRNA and protein levels of GLUT4 in the soleus muscle were increased after repeated intravenous administration of valsartan in STZ-diabetic rats for 3 days. Moreover, similar repeated treatment with valsartan reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. CONCLUSIONS: These results suggest that the plasma glucose-lowering activity of AT(1) receptor antagonism was associated with an increase in the glucose utilization in peripheral tissue and/or a reduction in hepatic gluconeogenesis in the absence of insulin.     

Antidiabetic potentials of the methanol leaf extract of Oxytenanthera abyssinica

Oxytenathera abyssinica is used for the treatment of diabetes mellitus in folklore medicine in Nigeria. In this study, we evaluated its antidiabetic activity in alloxan-induced diabetic mice. Diabetes was induced in the mice by a single intraperitoneal injection of alloxan monohydrate and the fasting blood glucose (FBG) levels measured with blood from the tail snip at 0, 1, 3 and 6 h. The activity was compared with reference drug, glibenclamide (2 mg/kg) and negative control. Oral glucose tolerance test (OGTT) was evaluated by loading glucose to rats at the dose of 2,000 mg/kg and checking their FBG at 0, 60 and 180 min. Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP) and 1, 1- diphenyl-2- hydrazyl (DPPH) photometric assay. The extract and the reference drug caused a significant (P?<?0.02–P?<?0.002) time and dose dependent decrease in the FBG levels of the mice when compared to the negative control; the extract (500 mg/kg) reduced FBG by 38.0 % at the 6th hr as against 45.6 % by glibenclamide. In OGTT the extract caused a time dependent decrease in the blood glucose level up to 33.3 % at 180 min at the dose of 300 mg/kg. The extract also caused a concentration dependent increase in antioxidant activity having 91 % increase and 1.95 total antioxidant activities at a concentration of 400 μg/ml. Extract of Oxythenanthera abyssinica showed significant antidiabetic activity.     

Antidiabetic activity of aqueous leaf extract of Atriplex halimus L. (Chenopodiaceae) in streptozotocin-induced diabetic rats

Objective

To investigate the antidiabetic effect of A. halimus leaf in streptozotocin-induced diabetic rats.

Methods

The aqueous extract of the plant leaf was tested for its efficacy in streptozotocin-induced diabetic rats. The extract was evaluated for its acute and short term general toxicity in male mice and for its antihyperglycemic activity using glucose tolerance test in rats. The aqueous extract was subjected to phytochemical screening and determination of total phenolic contents.

Results

The statistical data indicated the significant increase in the body weight and decrease in the blood glucose and hepatic levels. The total protein level was significantly increased when treated with the extract.

Conclusions

These results suggest that the aqueous leaf extract of A. halimus has beneficial effects in reducing the elevated blood glucose level and hepatic levels in streptozotocin-induced diabetic rats.     

Effects of co-administration of methanol leaf extract of Catharanthus roseus on the hypoglycemic activity of metformin and glibenclamide in rats

ObjectiveTo investigate the interacting effects of co-administration of methanol leaf extract of Catharanthus roseus (C. roseus) on the hypoglycemic activity of metformin as well as glibenclamide using experimental rats.MethodsPhytochemical analysis as well as acute toxicity and lethality (LD₅₀) test were carried out on its methanol leaf extract. The alloxan model for experimental induction of diabetes in rats was employed. Six groups comprising five rats each were used. Groups II, III and IV received 250 mg/kg of extract, 100 mg/kg of metformin and 1 mg/kg of glibenclamide respectively, while V and VI were administered metformin-extract and glibenclamide-extract combinations respectively at doses as above. Group I served as negative control and received only distilled water. All administration was done once daily for seven days. Fasting blood glucose was determined at 2, 12, 24, 72 and 168 h using a glucometer. One-way ANOVA with post-hoc tests was used to assess for significant difference due to administration of drug alone and with co-administration of drug and extract.ResultsThe LD₅₀ was 2 121.32 mg/kg. The phytochemical studies indicated the presence of saponins, tannins, alkaloids, phlotatannins, flavonoids, triterpenoids, reducing sugars, anthraquinones and glycosides. All medicaments significantly reduced blood glucose levels when compared with control alone (P<0.05) with the highest percentage reduction in blood glucose (64.86%) exhibited by metformin-extract combination.ConclusionsThe leaf extract of C. roseus significantly increases the hypoglycemic effect of metformin.     

Antidiarrheal activity of Pterocarpus erinaceus methanol leaf extract in experimentally-induced diarrhea

ObjectiveTo investigate the antidiarrheal activity of the methanol leaf extract of Pterocarpus erinaceus in vivo.MethodsThe methanol leaf extract of Pterocarpus erinaceus was evaluated using different doses (100, 200 and 400 mg/kg body weight) orally for antidiarrheal activity using castor oil-induced diarrhea, charcoal meal transit time and castor oil-induced enteropooling in different groups of albino Wistar mice. The activity of the extract at different doses were compared to diphenoxylate (5 mg/kg) and atropine sulphate (3 mg/kg) which were used as standard reference drugs and also to the distilled water administered negative control group of mice.ResultsThe extract at the doses used caused a significant (P< 0.01) reduction in the wet faeces passed by the mice in the castor oil-induced diarrhea, decreased the distance travelled by the charcoal meal by up to 54.8% and also caused a dose dependent and significant (P< 0.001) reduction in the intraluminal fluid accumulation in the castor oil-induced enteropooling.ConclusionsOur results indicate that Pterocarpus erinaceus extract produced significant antidiarrheal activity and the action may attribute to inhibition of gastrointestinal movement and fluid secretion.     

Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats

Momordica charantia (karela) is commonly used as an antidiabetic and antihyperglycemic agent in Asian, Oriental and Latin American countries. This study was undertaken to investigate the effects of long term feeding (10 weeks) of M. charantia fruit extract on blood plasma and tissue lipid profiles in normal and streptozotocin (STZ)-induced Type 1 diabetic rats. The results show that there was a significant (P < 0.05) increase in plasma non-esterified cholesterol, triglycerides and phospholipids in STZ-induced diabetic rats, accompanied by a decrease in high density lipoprotein (HDL)-cholesterol. A moderate increase in plasma (LPO) product, malonedialdehyde (MDA), and about two-fold increase in kidney LPO was also observed in STZ-induced diabetic rats. The treatment of diabetic rats with M. charantia fruit extract over a 10-week period returned these levels close to normal. In addition, karela juice also exhibited an inhibitory effect on membrane LPO under in vitro conditions. These results suggest that M. charantia fruit extract exhibits hypolipidemic as well as hypoglycemic effects in the STZ-induced diabetic rat.     

Phytochemical analysis, hepatoprotective and antioxidant activity of Alchornea cordifolia methanol leaf extract on carbon tetrachloride-induced hepatic damage in rats

ObjectiveTo investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A. cordifolia) leaf extract.MethodsVarious solvent fractions of the methanol extract of the leaf of the plant A. cordifolia Mull. Arg (Fam: Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT/AST), serum glutamate pyruvate transaminase (SGPT/ALT), alkaline phosphatase (ALP) and total bilirubin. The in vitro antioxidant activity of the extract was also evaluated by the 1, 1-diphenyl- 2-picrylhydrazyl (DPPH) free radical scavenging assay. The extract was subjected to preliminary phytochemical screening.ResultsThe ethyl acetate and chloroform fractions, at a dose of 300 mg/kg, produced significant (P<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. The effects were comparable to those of the standard drugs used for the respective experiments, silymarin and ascorbic acid. Alkaloids, flavonoids, saponins and tannins were detected in the phytochemical screening.ConclusionFrom this study, it was concluded that the plant of A. cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract.     

Antimalarial potency of the methanol leaf extract of Maerua crassifolia Forssk (Capparaceae)

ObjectiveTo investigate the in vivo antiplasmodial effect of methanol leaf extract of Maerua crassifolia in mice infected with chloroquine sensitive Plasmodium berghei berghei.MethodsThe extract was evaluated for activity against early infection, curative effect against established infection at dose levels of 100, 200 and 400 mg/kg p.o. Chloroquine at 10 mg/kg was used as standard drug.ResultsA dose dependent chemo-suppression of the parasites was obtained at different dose levels of the extract tested with a considerable mean survival time.ConclusionsThe results support continued investigation of components of traditional medicines as potential new antimalarial agents.     

Long-term effects of chitosan oligosaccharide in streptozotocin-induced diabetic rats

Streptozotocin has been used to induce an experimental model for diabetes to study the activity of anti-diabetic agents. The cholesterol-lowering effect of chitosan makes a continued issue in the field of diabetes, but the hypoglyecemic effect is inconclusive to date. Unlike chitosan, the water soluble chitosan oligosaccharide may possess various biological properties for diabetes. The present study was designed to investigate the long-term effects of chitosan oligosaccharide in normal and streptozotocin-induced diabetic rats using glycated hemoglobin and C-peptide. Chitosan oligosaccharide feeding did not cause any harmful effect on plasma glucose as well as plasma lipid metabolism in normal rats, although slightly elevated triglyceride was observed. As compared with the diabetic control rats, effects of chitosan oligosaccharide for 12 weeks in the diabetic rats were summarized as follows; (1) the blood glucose concentrations fell significantly and it was confirmed by decreased glycated hemoglobin, (2) the plasma C-peptide was increased and provided elevated degree of insulin secretion, and (3) relatively well reconstructed pancreatic islet with β-cells and additional insulin-immunolabeled cells in the pancreatic acinus and in the intercalated duct were observed. These results suggested that chitosan oligosaccharide could improve the altered blood glucose metabolism in the diabetic rats by various mechanisms such as accelerated proliferation or neogenesis of β cells and increased secretory capacity of insulin.     

Long-term effects of chitosan oligosaccharide in streptozotocin-induced diabetic rats

Streptozotocin has been used to induce an experimental model for diabetes to study the activity of anti-diabetic agents. The cholesterol-lowering effect of chitosan makes a continued issue in the field of diabetes, but the hypoglyecemic effect is inconclusive to date. Unlike chitosan, the water soluble chitosan oligosaccharide may possess various biological properties for diabetes. The present study was designed to investigate the long-term effects of chitosan oligosaccharide in normal and streptozotocin-induced diabetic rats using glycated hemoglobin and C-peptide. Chitosan oligosaccharide feeding did not cause any harmful effect on plasma glucose as well as plasma lipid metabolism in normal rats, although slightly elevated triglyceride was observed. As compared with the diabetic control rats, effects of chitosan oligosaccharide for 12 weeks in the diabetic rats were summarized as follows; 1) the blood glucose concentrations fell significantly and it was confirmed by decreased glycated hemoglobin, 2) the plasma C-peptide was increased and provided elevated degree of insulin secretion, and 3) relatively well reconstructed pancreatic islet with β cells and additional insulin-immunolabeled cells in the pancreatic acinus and in the intercalated duct were observed. These results suggested that chitosan oligosaccharide could improve the altered blood glucose metabolism in the diabetic rats by various mechanisms such as accelerated proliferation or neogenesis of β cells and increased secretory capacity of insulin.     

Potent hypoglycaemic activity of the aqueous extract of Chamaemelum nobile in normal and streptozotocin-induced diabetic rats

The purpose of this study was to investigate the effect of both a single dose and daily oral administration for 15 days of the aqueous extract of the aerial part of Chamaemelum nobile (C. nobile) at a dose of 20mg/kg body weight on blood glucose concentrations and basal insulin levels in normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of C. nobile aqueous extract reduced blood glucose levels from 6.0 +/- 0.3 mmol/l to 4.9 +/- 0.09 mmol/l (P < 0.05) 6h after administration in normal rats and from 21.1 +/- 1.3 mmol/l to 14.5 +/- 0.9 mmol/l (P < 0.001) in STZ diabetic rats. Furthermore, blood glucose levels were decreased from 6.1 +/- 0.06 mmol/l to 4.6 +/- 0.17 mmol/l (P < 0.01) and from 21.1 +/- 1.31 mmol/l to 13.7 +/- 0.9 mmol/l (P < 0.01) in normal and STZ diabetic rats, respectively, after 15 days of treatment. Basal plasma insulin concentrations remain unchanged after treatment in both normal and STZ diabetic rats so the mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of C. nobile exhibits a significant hypoglycaemic effect in normal and STZ diabetic rats without affecting basal plasma insulin concentrations and support, therefore, its traditional use by the Moroccan population.     

Early treadmill exercise decreases intrastriatal hemorrhage-induced neuronal cell death and increases cell proliferation in the dentate gyrus of streptozotocin-induced hyperglycemic rats

Intracerebral hemorrhage (ICH) is a severe complication in diabetic patients. Currently, physical exercise is recommended as a behavioral intervention to promote functional recovery in brain diseases, including ICH. Recently, hyperglycemia is known to aggravate brain injury in experimental ICH. Here, we examined the effect of treadmill exercise on the intrastriatal hemorrhage-induced neuronal cell death and cell proliferation in the dentate gyrus of hyperglycemic rats. Hyperglycemia was induced by the intraperitoneal injection of 50 mg/kg streptozotocin (STZ). Intrastriatal hemorrhage was induced by the infusion of 0.2 U collagenase into the striatum using stereotaxic instrument. Rats in the exercise groups were forced to run on a treadmill for 30 min daily for 10 days. Apoptosis was assessed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Cell proliferation was assessed by the 5-bromo-2′-deoxyuridine (BrdU) immunohistochemistry. Our data showed that in rats started treadmill exercise 24 h after ICH induction, the size of lesion induced by hemorrhage and the number of apoptotic cells were decreased significantly. The number of proliferating cells in the dentate gyrus was significantly decreased in hyperglycemic rats. Treadmill exercise markedly enhanced cell proliferation in the dentate gyrus of hyperglycemic rats. The data suggest that treadmill exercise may provide therapeutic value to ICH patients with hyperglycemia by suppressing neuronal apoptosis and increasing cell proliferation.     

吡格列酮对高血糖肥胖大鼠胰岛素敏感性及脂联素水平的影响

吡格列酮应用于肥胖和高血糖大鼠，能改善正糖钳夹试验所证明的胰岛素敏感性，升高脂联素水平，降低肿瘤坏死因子α(TNF-α)和游离脂肪酸(FFA)血水平     

Neuroprotective effects of Pouteria ramiflora (Mart.) Radlk (Sapotaceae) extract on the brains of rats with streptozotocin-induced diabetes

Diabetes mellitus is a chronic disease involving persistent hyperglycemia, which causes an imbalance between reactive oxygen species and antioxidant enzymes and results in damage to various tissues, including the brain. Many societies have traditionally employed medicinal plants to control the hyperglycemia. Pouteria ramiflora, a species occurring in the savanna biome of the Cerrado (Brazil) has been studied because of its possible ability to inhibit carbohydrate digestion. Rats with streptozotocin-induced diabetes treated with an alcoholic extract of Pouteria ramiflora show an improved glycemic level, increased glutathione peroxidase activity, decreased superoxide dismutase activity, and reduced lipid peroxidation and antioxidant status. The extract also restored myosin-Va expression and the nuclear diameters of pyramidal neurons of the CA3 subregion and that of the polymorphic cells of the hilus. We conclude that Pouteria ramiflora extract exerts a neuroprotective effect against oxidative damage and myosin-Va expression and is able to prevent hippocampal neuronal loss in the CA3 and hilus subfields of diabetic rats. However, future studies are needed to understand the mechanism of action of Pouteria ramiflora extract in acute and chronic diabetes.     

Gastroprotective effect of the aqueous leaf extract of Guiera senegalensis in Albino rats

ObjectiveTo evaluate the effect of aqueous leaf extract of Guiera senegalensis (G. senegalensis) on gastric mucosal damage using different ulcer models.MethodsConsidering the above claims, the present study was undertaken to validate the gastroprotective potential of the aqueous leaf extract of this plant against ethanol, water immersion and Aspirin induced ulcer models.ResultsThe leaf extract (50, 100 and 200 mg/kg, p.o.) significantly (P<0.05) decreased the ulcer index in all assays used.ConclusionsThe results obtained, provide strong evidence of antiulcer activity of the leaf extract of G. senegalensis and support the traditional uses of the plant for the treatment of ulcer.     

Antihyperglycemic effect of Passiflora glandulosa cav. fruit rinds flour in streptozotocin-induced diabetic mice

Objective:To investigate the effect of administration of Passiflora glandulosa(P.glandulosa) fruit rinds flour on streptozotocin(STZ)-induced diabetic mice.Methods:The preliminary phytochemical screening and parameters such as centesimal composition and brine shrimp toxicity were evaluated.For in vivo study Swiss female mice were divided into four groups:NC-normal control;DC-diabetic control animals receiving saline;MET-diabetic animals receiving metformin(200 mg/kg);PFRF-diabetic animals receiving P.glandulosa fruit rinds flour(200 mg/kg).All of them were treated for 28 d.STZ was used in a single dose of 120 mg/kg to establish diabetic models.Body weight,water and food intake,fasting blood glucose were measured.Histopathological analysis of pancreas and liver were performed to evaluate STZ-induced tissue injuries.Results:Phytochemical screening showed the presence of flavanones and triterpenoids.The P.glandulosa fruit rinds flour was non-toxic by the brine shrimp test.The fruit rinds flour also reduced the loss of body weight and significantly decreased food intake in the diabetic mice.Additionally,a significant reduction in blood glucose was observed for 15 d and this was maintained on 21 d and 28 d when compared with diabetic mice.Furthermore,the P.glandulosa fruit rinds flour has a favourable effect on the histopathological changes of the pancreas in STZ induced diabetes.Conclusions:It is concluded that P.glandulosa fruit rinds flour is a natural product that contains potent antioxidant compounds and presents good prospects for the improvement of diabetic mellitus by reducing serum glucose levels.     

Hypoglycemic,hypolipidemic, and hepatoprotective effects of Polyscias fulva (Hiern) Harms ethanolic bark extract in streptozotocin-induced diabetic Wistar rats

International Journal of Diabetes in Developing Countries - Polyscias fulva (Hiern) Harms stem bark is used in traditional folk medicine in Kenya for diabetes mellitus and obesity management. This...