Normoglycemic Rats Research Articles

The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3',4'-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease.

The aim of this study was to analyze the possible nephroprotective effect of 3',4'-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7-7.8% reduction in DHPG-treated rats), as well as 38-56% reduction in urinary protein excretion and 22-46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson's coefficient 0.68-0.74), antinitrosative (Pearson's coefficient 0.83), and prostacyclin production regulator (Pearson's coefficient 0.75) effects.

Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT1D Receptor Activation via NO Pathway.

Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT1/5/7 agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT1D agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT1D antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT1D receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.

Effects on Blood Glucose of Ethyl Acetate-Butanol Fraction of Dialium guineense Aqueous Leaf Extract (Cesalpiniaceae)

Introduction: The overall objective of the study was to evaluate the effect on blood glucose of the ethyl acetate-butanol fraction (EABF) compounds of the aqueous leaf extract of Dialium guineense (Cesalpiniaceae).
 Materials and Methods: The powder of D. guineense leaves was subjected to decoction. The aqueous solution was respectively fractionated with ethyl acetate and butanol. The sub-fractions were grouped to form the ethyl acetate-butanol fraction (EABF), enriched in flavonoids and tannins. The condensed tannins of EABF were eliminated under the action of casein, resulting in a condensed tannin-free fraction (EAB-TFF). EABF and EAB-TFF were phytochemically characterized and tested in normo-glycemic rats, a glucose tolerance test and type 2 diabetic rats.
 Results, Analysis and Discussion: EABF (300 mg/kg, per os) has no significant effect on blood glucose in normo-glycemic rats (0.80±0.12 vs 0.81±0.01 g/L). Under the same conditions, EABF without tannins (EAB-TFF: 300 mg/kg, per os) is hypoglycemic (0.57±0.05 vs 0.82±0.05 g/L). These results suggest the existence of an antagonism, in the effects on blood glucose, between tannins and probably flavonoid-like compounds. In type 2 diabetic rats, the daily administration of EABF (300 mg/kg/day, per os) varied blood glucose from 2.73±0.39 to 1.14±0.58 g/L (n=5, p<0.05). Similar effects were observed with EAB-TFF (300 mg/kg/day, per os), administered under the same conditions (1.12±0.04 g/L vs 3.01±0.5 g/L) (p<0.05, n=5). EABF has no effect on blood glucose in normo-glycemic rats, whereas under the same conditions, EAB-TFF induces an hypoglycemic effect. These results suggest the existence of compounds acting in opposite directions, in the regulation of blood glucose.

Anti-hyperglycemic potential and chemical constituents of Aristolochia triangularis Cham. leaves − A medicinal species native to Brazilian forests

Ethnopharmacological relevanceAristolochia triangularis Cham. has been used in Brazilian traditional medicine for various therapeutic purposes, including as a leaf-based infusion for diabetes management. Aim of the study: This study was designed to chemically characterize an infusion of in natura A. triangularis leaves and evaluate the in vivo anti-hyperglycemic properties of this infusion. Materials and methods: Chemical composition was examined using liquid–liquid extraction procedure, chromatographic methods, NMR, and LC−MS/MS. The in vivo anti-hyperglycemic activity of the freeze-dried infusion of A. triangularis leaves (Inf-L-At) was assessed using oral glucose tolerance test (OGTT). Initially, normoglycemic male rats were pre-treated with orally administered Inf-L-At at doses of 62.5, 125, and 250 mg/kg for two consecutive days. On the day of the OGTT, fasting animals received a glucose load (4 g/kg) 30 min after treatment with Inf-L-At, and the blood glucose levels were verified at 15, 30, 60, and 180 min. Intestinal maltase, lactase, and sucrase activities and muscle and liver glycogen contents were also assessed after the OGTT. Results: Inf-L-At extract led to glycemic reduction with no dose-response at 15, 30, and 60 min comparable to that of the antidiabetic drug glibenclamide and was accompanied by an increase in hepatic and muscle glycogen contents. Additionally, there was a significant statistically decrease in the in vitro activity of disaccharidases. Maltase and sucrase activities were inhibited at all doses, whereas lactase activity was inhibited only at 62.5 and 250 mg/kg. In total, 75 compounds were found in the infusion, including seven new ones, (7S*,8S*,7ꞌS*,8ꞌR*)-4,4ꞌ-dihydroxy-3,3ꞌ-dimethoxy-7,9ꞌ-epoxylignan-7ꞌ-ol; 4ꞌ-hydroxy-3ꞌ-methoxy-3,4-methylenedioxy-7,9ꞌ-epoxylignan-9,7ꞌ-diol; triangularisines A, B, and C; N-ethyl-N-methyl-affineine; and N-methyl pachyconfine, and one previously not described as a natural product, epi-secoisolariciresinol monomethyl ether. Conclusion: The results demonstrated the anti-hyperglycemic activity of the infusion from A. triangularis leaves and showed that it is a rich source of lignoids, alkaloids, and glycosylated flavonoids, which are known to exhibit antidiabetic effects and other biological properties that can be beneficial for patients with chronic hyperglycemia, thus certifying the popular use of this herbal drink.

LC-MS-based metabolite profiling of aqueous extract of Pergularia tomentosa L. and its anti-hyperglycemic effect.

In this study, to find scientific evidence for the traditional use of Pergularia tomentosa as an anti-diabetic remedy, the effects of its aqueous extract on streptozotocin-induced diabetes mellitus in rats were evaluated. Wistar rats were fasted overnight and diabetes mellitus was induced using streptozotocin (50 mg/kg body weight). The rats were randomly and equally divided into four groups (n=5): group I (normoglycaemic control), group II (diabetic rats), group III (diabetic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa), group IV (normoglycemic rats treated with 200 mg/kg BW of an aqueous extract of P. tomentosa). Chemical profiling of the aqueous extract was carried out using liquid chromatography coupled with electrospray ionization and multiple-stage linear ion-trap and orbitrap high-resolution mass spectrometry (LC-ESI/LTQOrbitrap/MS/MS). In addition, the quantitative determination of the main cardenolides in the extract was carried out by an analytical approach based on LC coupled to tandem mass spectrometry with ESI source and hybrid triple quadrupole-linear ion trap mass analyzer (LC-ESI/QTrap/MS/MS). Aqueous extract of P. tomentosa showed a reasonable reduction in blood glucose level. Probably, the P. tomentosa effect on hyperglycemic and hyperlipidemic diabetic animals was associated with antioxidant properties, triglyceride levels, as well as liver enzymes. Meanwhile, LC-ESI/LTQOrbitrap/MS/MS analysis led to identification of double-linked cardenolides along with cardenolides and flavone glycosides as the main bioactive compounds. The extract decreased the glucose level and induced a beneficial effect on the lipid profile, probably due to the presence of cardenolide glycosides.

Effect of Pulicaria mauritanica on Glucose Metabolism and Glycogen Content in Streptozotocin-Induced Diabetic Rats.

The study aimed to assess the antihyperglycemic activity of Pulicaria mauritanica. Pulicaria mauritanica is a medicinal and aromatic plant used for the treatment of many diseases such as inflammation, diabetes, and intestinal disorders. The main goals of this present paper were to confirm the antihyperglycemic capacity of aqueous extract from Pulicaria mauritanica in normoglycemic and diabetic rats over a period of time (7 days of treatment). The effect of the aqueous extract of Pulicaria mauritanica from aerial parts (AEPM) on glucose and lipid metabolism was tested using an acute test (single dose during 6 hours) and subchronic assay (repeated oral administration for seven days) at a dose of 60 mg/kg and the serum glucose levels were measured in normoglycemic and streptozotocin(STZ)-induced diabetic rats. In addition, the glycogen content in the liver, extensor digitorum longus (EDL), and soleus was evaluated. The antioxidant activity, phytochemical screening, and quantification of some secondary metabolites of this extract were also performed. AEPM at a dose of 60 mg/kg reduced the plasma glucose concentrations significantly in STZ-induced diabetic rats after a single oral administration (p<0.05). This lowering effect became more significant during the repeated oral administration in hyperglycemic rats (p<0.0001). Also, the findings showed that this plant exhibited a significant increase in liver and skeletal soleus muscle glycogen content in diabetic rats. AEPM revealed a remarkable antioxidant activity in addition to the presence of polyphenol compounds such as flavonoids, tannins, saponins, sterols, glucides, terpenoids, quinones, anthraquinones, and mucilage. The study shows that AEPM exhibits antihyperglycemic activity in diabetic rats, and it increases liver and muscle glycogen content.

Potential cerebrovascular protective functions of lycium barbarum polysaccharide in alleviating hyperglycemia-aggravated cerebral ischemia/reperfusion injury in hyperglycemic rats.

Lycium barbarum polysaccharide (LBP) is the efficient primary compound of Lycium barbarum and has been shown to alleviate hyperglycemia-aggravated cerebral ischemia/reperfusion (I/R) injury. However, the cerebrovascular changes related to diabetes mellitus (DM) and the potential cerebrovascular protective effects of LBP are still unknown. This study aimed to explore the cerebrovascular protective functions of LBP on cerebral I/R injury in diabetic rats and its potential mechanisms. Sprague Dawley (SD) rats were separated into three groups: the normoglycemic (NG), diabetic hyperglycemic (HG), and HG + LBP (50 mg/kg) treatment groups. A 30 min transient middle cerebral artery occlusion (tMCAO) with 24 h reperfusion was established. The neurological deficits, cerebral water content, infarct volume, and cerebrovascular permeability were assessed to evaluate the extent of cerebral injury. Histopathological alterations were assessed by hematoxylin and eosin, Nissl, immunohistochemical, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. A transmission electron microscope was used to detect ultrastructural alterations, and a western blot was used to examine protein expression. The HG rats exhibited a significant increase in neurological deficits, cerebral water content, infarct volume, cerebrovascular permeability, neural cell death, and apoptosis compared with the NG rats, and the LBP treatment alleviated these effects. Cerebrovascular structure analysis showed that the cross-sectional area (CSA) and wall thickness were remarkably altered in the HG rats compared with the NG rats. The LBP treatment protected the cerebrovascular structure and vasoreactivity by decreasing the wall thickness and increasing the CSA, α-smooth muscle actin, and endothelial nitric oxide synthase expression of cerebral vessels. The intake of LBP benefits the cerebrovascular structure and vasoreactivity in diabetic rats. Our research provides a possible new strategy for treating stroke in patients with DM.

Antidiabetic Potential and Antioxidant Activity of Olea europaea subsp. Cuspidata (Indian Olive) Seed Extracts.

The aim of the present study was to evaluate the antioxidant and antidiabetic potential of Indian olive seed extracts. Plant seeds were sequentially extracted with n-hexane, chloroform, methanol, and water. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging and alpha-amylase inhibitory activities of extracts were carried out. Olea europaea methanolic extract (MEOE) and aqueous extract (AEOE) were orally administered to normoglycemic and alloxan-treated diabetic rats so as to determine their hypoglycemic effect. High-performance liquid chromatography (HPLC) analysis showed gallic acid, ferulic acid, quercetin, and vanillic acid in MEOE. It was found that the methanolic and aqueous extracts exhibited the maximum DPPH and alpha-amylase inhibition activities, respectively. MEOE and AEOE exerted a significant decline in the fasting blood sugar in diabetic animals (p < 0.05); however, they did not cause hypoglycemia in nondiabetic animals. Treatment with MEOE and AEOE reduced the aggravated liver and kidney function biomarkers. Aggravated levels of oxidative stress biomarkers including superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and malondialdehyde (MDA) were restored by treatment with MEOE. Moreover, MEOE improved the count of islets of Langerhans in the pancreas, fatty changes, and enlarged sinusoidal spaces in the liver and necrosis of the glomerulus and tubular cells of the kidney in diabetic rats. This study showed that the African olive seed extract effectively managed experimental diabetes and restored the normal functions and histology of the liver and kidney in diabetic rats through the reduction of oxidative stress.

Studies on Hypoglycaemic activity of the different extracts of Solanum torvum root

The objective of the study was to Studies on the hypoglycaemic activity of the different extracts of Solanum torvum (Solanaceae) root extracts on Wister albino rats. Solanum torvum roots were shade dried, powdered, and extracted by the Soxhlet extraction procedure using petroleum ether, chloroform, ethanol, and water. Swiss albino mice were chosen for the acute toxicity studies and follow the OECD guidelines 423. The hypoglycemic activity on adult Wistar albino rats at dose levels of 100, 200, and 400mg/kg p.o. respectively each using normoglycaemic, glucose loaded, and streptozotocin-induced hyperglycaemic rats. For activity comparison standard drug Metformin (150mg/kg) was used. Promising results were produced by the ethanol extract among all the tested extracts that are comparable to the reference standard metformin. The study entrenched the scientific foundation of the benefits of this plant in the medication of diabetes and asserts the use of the root of the plant for treating diabetes as demonstrate in folklore remedies.

The Effect of Metformin on Ethanol- and IndomethacinInduced Gastric Ulcers in Rats.

Background:Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies.Methods: After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1β level.Results:In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups.Conclusion:The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.

Effects of salvianolic acid A on intestinal microbiota and lipid metabolism disorders in Zucker diabetic fatty rats

Salvianolic acid A (SalA) is the main water-soluble component isolated from Salvia miltiorrhiza. This study explored the influences of SalA on intestinal microbiota composition and lipid metabolism in Zucker diabetic fatty (ZDF) rats. The 6-week-old male ZDF rats were treated with distilled water (N = 10) and low dose (SalA 0.5 mg/kg/d, N = 10), medium dose (SalA 1 mg/kg/d, N = 10), and high dose (SalA 2 mg/kg/d, N = 10) of SalA, with the male Zucker lean normoglycemic rats of the same week age as controls (given distilled water, N = 10). The blood glucose, body weight, and food intake of rats were examined. After 7 and 8 weeks of continuous administration, oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed, respectively. Serum fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) were determined. Liver tissues were stained using hematoxylin–eosin (HE) and oil red O staining. Fecal samples were analyzed by 16S rRNA gene sequencing. Small intestinal tissues were stained using HE and immunohistochemistry. The tight junction proteins (ZO-1/Occludin/Claudin-1) and serum levels of LPS/TNF-α/IL-6 were evaluated. SalA reduced insulin resistance, liver injury, serum FFA, liver TC and TG levels in ZDF rats, and improved lipid metabolism. After SalA treatment, intestinal microbiota richness and diversity of ZDF rats were promoted. SalA retained the homeostasis of intestinal core microbiota. SalA reduced intestinal epithelial barrier damage, LPS, and inflammatory cytokines in ZDF rats. Overall, SalA can sustain intestinal microbiota balance and improve the lipid metabolism of ZDF rats.

In-vivo evaluation and formulation development of polyherbal extract in streptozotocin-induced diabetic rat

BackgroundThe research focuses on polyherbal antidiabetic extracts from various plants that are utilized in the management of type 2 diabetes mellitus at various doses. Ayurvedic treatment is widely accepted throughout due to their efficacy, safety, less price, ubiquity, and acceptance. Polyherbal medicines, contain glycosides, alkaloids, flavonoids, and other compounds that have unique mode of action to treat diabetes, have long been used across the world. This study was carried out to investigate the hypoglycemic effects and antihyperglycemic activity of polyherbal (PH) extract in streptozotocin (STZ)-induced diabetic rats. Along with this, the antioxidant and antihyperlipidemic activity of Polyherbal extract (PH) were also studied. Further, polyherbal tablets were formulated and evaluated. MethodPolyherbal extract (hydroalcoholic) was tested for the hypoglycemic activity for 4 h in normoglycemic rats, oral glucose tolerance test (OGTT) (2 h), and antihyperglycemic activity (28 days) in non-diabetic and STZ-induced diabetic rats. Further, antihyperlipidemic and antioxidant activity were also studied along with histopathology and pre & post-compression tablet data. The effective antidiabetic activity was observed for PH I (400 mg/kg followed 200 mg/kg). OGTT has shown that PH I (200 mg/kg) extract is having a better glucose utilization capacity. The data also propose that PH I (400 mg/kg followed 200 mg/kg) exhibit significant and consistent hypoglycemic activity. ResultsOur findings explain that polyherbal extract in variant doses has antihyperlipidemic and antioxidant activity, which is manifested by decreasing total cholesterol, triglyceride, LDL, VLDL and MDA level. The extract also increased the HDL, SOD and reduced glutathione level in various treatment groups. The data propose that the combined extract showed a consistent and ameliorated hepatic and renal function, in the treatment groups. Polyherbal extract PH I (400 mg/kg) have manifested the most effective improvements in diabetic complications. All the pre & post-compression tablet data were within limits. The above results propose that this Polyherbal extract may be a potential source for the development of the new antidiabetic drug. ConclusionsThe proposed activity of the polyherbal extract is supported by various biochemical and histopathologic analyses. By examining its safety and in vivo efficacy, the combination of ayurvedic components will give us a novel glimmer of hope for the lifestyle illness.

HYPOGLYCAEMIC AND ANTIHPERGLYCAEMIC ACTIITIES OF AQUEOUS EXTRACT OF FICUS CARICA IN DIABETIC RATS

The Ficus carica ( fig ) is an important harvest worldwide for its dry and fresh consumption. Its common edible part is the fruit which is fleshy, hollow, and receptacle . The dried fruits of Ficus carica have been reported as an important source of vitamins, minerals, carbohydrates, sugars, organic acids, and phenolic compounds A short study was undertaken as a preliminary investigation to evaluate the antidiabetic effect of the aqueous leave extract by oral glucose tolerance test (OGTT) , normoglycemic and antihyperglycemic activity in streptozotocin (STZ)-nicotinamide in a dose of 120 mg kg induced non insulin-dependent diabetes mellitus Wister albino rats. Graded doses (250 and 500 mg/kg) of the aqueous leave extract suspended in gum acacia were administered to normal and experimental diabetic Wister albino rats. Effect on glucose tolerance test showed a significant reduction in the blood glucose level of extract treated animals after 1 hr, indicating its hypoglycemic activity. Continuous blood glucose lowering activity was observed till 4 hr of administration in normoglycemic and diabetic rats. The results were compared with standard drug glibenclamide. Also the extract showed a high LD50 value and could be used safetly.

Caffeic acid abrogates amyloidosis, hypospermatogenesis and cell membrane alterations in the testes and epididymis of fructose-diabetic rats by upregulating steroidogenesis, PCNA and Nrf2 expression

The fructose-streptozotocin (FRU-STZ) diabetic model has been presented as a viable model of type2 diabetes but its impact on the testes and epididymis of Wistar rats is yet to be investigated. In this study, we probed the role of caffeic acid, a potent antioxidant, in FRU-STZ diabetic rats. Twenty normoglycemic rats were randomly divided into four groups of five rats each: Control, Fructose-Streptozotocin (FRU+STZ), Fructose-Streptozotocin + Caffeic Acid (FRU+STZ+CA), and Caffeic Acid (CA). Diabetes was induced by the administration of 10 % fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of 50 mg/kg bwt of streptozotocin. Treatment with CA (50 mg/kg bwt) lasted for two weeks. Results showed that FRU-STZ diabetes was able to induce amyloidosis and histopathological deficits in the testis and epididymis characteristic of cytotoxic agents. Poor PCNA immunoreactivity, reactive Nrf2 expression, and defective steroidogenesis were also observed in the diabetic group. FRU-STZ diabetes was also associated with significantly increased Na+-K+ ATPase activity in both testes and epididymis. Treatment with caffeic acid was able to restore steroidogenesis and spermatogenesis in the diabetic rats to levels comparable to the control; histological features and Na+-K+ ATPase activity were also reduced in the CA-treated group. Generally, normal rats treated with caffeic acid did not evince any deleterious effects. Our study demonstrates that CA exerts a protective role in FRU-STZ diabetes.

In vivo evaluation of wound healing effect and antioxidant properties of extracts and fractions of Gymnema sylvestre

Among the causes of mortality, wound healing remains a major problem that often results from imbalance between prooxidants and endogenous antioxidants in diabetics. The aim of this study was to evaluate the wound healing activity of Gymnema sylvestre in normoglycemic rat, and its antioxidant properties in type 2 diabetic rat. Evaluation of the healing properties of extracts (aqueous and methanol) and fractions (methylene chloride and methanol) G. sylvestre (10% of fraction or extract) were conducted in female normoglycemic rats and 1% fluoxetine was considered positive control using glycerin as a vehicle, while antioxidant assessments were conducted in male diabetic rats. Type 2 diabetes was induced in male rats by a high sucrose diet for 12 weeks followed by daily intraperitoneal injection of dexamethasone (8 mg/kg) for 5 consecutive days. Animals with a blood glucose above or equal to 140 mg/kg after 12 hours of fasting were considered diabetic. For the evaluation of wound healing 5 groups consisting of 3 female rats each were formed. Fluoxetine (1%), aqueous (Aq) and methanol (MeOH) extracts as well as methylene chloride (F1) and methanol (F2) fractions of the plant were administered at 10% via utopian application on wounds of about 2.5 cm in diameter. For the estimation of oxidative stress parameters in the diabetic rat, 7 groups of 5 animals each were formed, with three control groups including two negative control groups (normoglycemic and diabetic) receiving the vehicle orally (DMSO 3%) and a positive control group receiving metformin (Met, 200 mg/kg). The four experimental groups were treated orally with administration of Aq (100 mg/kg), MeOH, F1 and F2 (7.5 mg/kg). The different treatments were administered once a day for 14 consecutive days. Results showed that G. sylvestre promoted wound healing (P&gt;0.05) in the normoglycemic rat with a stronger effect for F2 and MeOH compared to the untreated group. In the diabetic rat, extracts and fractions of G. sylvestre significantly reduced (P&lt;0.001) the MDA level, while F1 significantly increased (P&lt;0.01) the activity of catalase (CAT) and reduced glutathione (GSH) compared to the untreated diabetes group on day one. These results revealed that G. sylvestre exhibited strong wound healing effects and justify the use of this in traditional pharmacopoeia.

ASSESSMENT OF INULA CAPPA LEAVES EXTRACTS FOR ANTIDIABETIC POTENTIAL IN EXPERIMENTAL ANIMALS

Diabetes mellitus (DM) is a long-term disease that can be caused by a lack of insulin production by the pancreas, or by the ineffectiveness of the insulin produced. For the study, the antidiabetic effects of methanolic and 50% v/v hydroalcoholic methanolic and extracts of the leaves of Inula cappa were used as oral doses at 100, 200, and 400 mg/kg and Metformine (50 mg/kg) were administered continuously for 21 days as a single morning dose. 18 hours of fasting was used to assess the drug's anti-diabetic effects in normoglycemic rats. On the 0th, 10th, and 21st days of the experiment, glucose oxidase method readings were collected using an autoanalyzer to assess fasting blood glucose levels. Anti-oxidant parameters were determined including, total phenolic content, total flavonoid concentration, DPPH free radical scavenging activity, Hydroxyl radical scavenging activity, Scavenging of Hydrogen Peroxide, Superoxide radical scavenging assay, Nitric oxide scavenging activity and Reducing power assay. The methanolic (ICME) and hydroalcoholic (ICHE) extracts of Inula cappa leaves (100, 200, and 400 mg/kg, p.o.) passes the Oral Glucose Tolerance Test. Both extracts had a greater impact in lowering blood glucose levels. Out of which ICHE at all doses showed significant effect (P&lt;0.05-P&lt;0.001) when compared with control. ICME in terms of glucose tolerance at all doses had significant effects. Keywords: Diabetes mellitus, insulin, metformine, scavenging, Inula cappa.

Streptozotocin-induced diabetes in rats modifies the role D2 , D3 and D4 dopamine receptors play in cardiac sympathetic inhibition.

Diabetes mellitus is associated with abnormalities in peripheral/central catecholaminergic systems, including changes in catecholamine levels and receptor expression. Since quinpirole-induced cardiac sympathetic inhibition is greater in diabetic than in normoglycemic rats, this study pharmacologically investigated the dopamine D2 -like receptor subtypes that mediate cardiac sympathetic inhibition in diabetic (streptozotocin [STZ]-pretreated) pithed rats. Fifty male Wistar rats were pretreated with STZ, pithed and conditioned for spinal stimulation (C7 -T1 ) of the tachycardic sympathetic tone. The resulting increases in heart rate were evaluated following i.v. blocking doses of antagonists at D2 , D3 and D4 receptors during a continuous i.v. infusion of quinpirole (an agonist at D2 -like receptors) or saline (vehicle). With this experimental approach, the cardiac sympathetic inhibition produced by quinpirole in diabetic rats was:(i) unchanged after administration of vehicles and; (ii) abolished by the antagonists L-741,626 (D2 ), SB-277011-A (D3 ) or L-745,870 (D4 ). These findings in diabetic pithed rats imply that: (i) the cardiac sympathetic inhibition by quinpirole involves activation of D2/3/4 dopamine receptors; and (ii) there is a differential stimulation of these receptors compared to normoglycemic rats. These D2/3/4 receptor subtypes could be a novel drug target for the therapy of typical cardiac complications of diabetes.

Antihyperglycemic effects of Amrtottara Kvatha, an Ayurvedic polyherbal formulation in streptozotocin-induced diabetic rats by suppressing oxidative stress

Amrtottara Kvatha [KNM3] (AK) is a widely used Ayurvedic preparation, primarily utilized for hyperpyrexia (‘Jwara’). In the present study we evaluated the antidiabetic effect of AK against streptozotocin (STZ) induced diabetic murine model. The effects of AK on normoglycemic rats and glucose tolerance were also studied. The antidiabetic effect of AK was evaluated in streptozotocin (STZ, 55 mg/kg, i.p.) induced diabetic rats. AK was administered orally at four doses AK (1/4), AK (1/2), AK (T) and AK (DD) for fourteen days to examine the antidiabetic activity with glibenclamide (5 mg/kg) as reference standard. The effect of AK on blood glucose and insulin levels, biochemical parameters, oxidative stress biomarkers and histopathological examinations were studied. Oral administration of AK at doses AK (1/4), AK (1/2), AK (T) and AK (DD) to rats with streptozotocin induced diabetes showed significant (P&lt;0.01) decrease in blood glucose levels with improved insulin levels, liver glycogen and pancreatic protein content. The oxidative stress biomarkers (malondialdehyde and advanced oxidation protein products) were reduced in all AK treated groups with a significant (P&lt;0.01) increase in antioxidant enzyme status. Histopathological studies also supported the findings. The present study reports for the first time the antidiabetic effects of Amrtottara Kvatha by suppressing oxidative stress induced by streptozotocin in Wistar rats.

Prospective role of α2A/2B/2C-adrenoceptor subtypes in the modulation of cardioaccelerator sympathetic tone in an experimental model of diabetes

Abnormalities in the cardiac sympathetic innervation and tone, as well as in the noradrenergic system are associated, among other peripheral complications, with diabetes mellitus. Furthermore, B-HT 933, an agonist at α2-adrenoceptors, induces a greater cardiac sympathetic inhibition in diabetic rats than in normoglycaemic rats. Accordingly, this pharmacological study analysed the specific involvement of the α2A/2B/2C adrenoceptor subtypes mediating inhibition of the cardioaccelerator sympathetic tone (i.e. cardiac sympathetic inhibition) in an experimental model of diabetes induced by streptozotocin (STZ). Fifty male Wistar rats were consecutively: injected i.p. with STZ to cause diabetes; pithed after four weeks; and primed for electrical preganglionic stimulation (spinal C7-T1 segment) to selectively produce increases in heart rate. These responses were evaluated after i.v. bolus injections of relatively selective α2A-, α2B- and α2C-adrenoceptor antagonists (or vehicles) during an i.v. continuous infusion of B-HT 933 or vehicle. B-HT 933 produced a significant inhibition of the sympathetic tachycardic responses, which was: (i) unaffected after the vehicles saline or dimethyl sulfoxide (DMSO); (ii) partially attenuated after blocking doses of the antagonists BRL44408 (α2A) or JP-1302 (α2C); and (iii) abolished after blocking doses of the antagonist imiloxan (α2B). These findings in diabetic pithed rats indicate that the modulation of the cardioaccelerator sympathetic tone predominantly involves the α2B-adrenoceptor subtype and, to a lesser degree, the α2A- and α2C-adrenoceptor subtypes. Hence, blockade of the sympatho-inhibitory α2B-adrenoceptor subtype (absent in normoglycaemic rats) could denote a novel pharmacological strategy for the therapy of some cardiac disorders during the early stages of diabetes.

Antidiabetic and Antiradical Effects of Garcinia kola Seeds in Dexamethasone-Induced Hyperglycemic Rats

BackgroundIn traditional medicine, the maceration of seeds of Garcinia kola (GK) is used to treat various diseases including diabetes. In traditional pharmacopoeia, GK seeds are used to strengthen the immune system and as a stimulant and aphrodisiac.AimsThis study aimed to evaluate the antidiabetic free radical scavenging effects of the hydroalcoholic extract of GK seeds (HAEGS) in a dexamethasone-induced hyperglycemic (DexIH) rat model.Settings and DesignThis study was an interventional study.Subjects and MethodsHere using in vivo model, we assessed some pharmacological properties of HAEGS in DexIH rat. Hypoglycemia, antihyperglycemia, spasmolytic and laxative activities were also evaluated in DexIH. In vitro study assessed antiradical activity. The HAEGS was obtained by decoction introducing 250 g with water–ethanol mixture (30:70). The plant extract was administered to the animals at doses of 50 (GK50) and 100 (GK100) mg/kg body weight. All animal experiments were in accordance with ARRIVE guidelines and were performed in accordance with the scientific procedures of UK Animals. Antiradical activity of GK was assessed in vitro by inhibition of the activity of 2,2-diphenyl-1-picrylhydrazyl.Statistical Analysis UsedStatistical analysis was performed using GraphPad Prism 5.03 software, and P values less than 0.05 were considered statistically significant.ResultsAt doses 50 and 100 mg/kg, GK significantly (P < 0.001) regulated DexIH after two weeks of treatment compared to the normoglycemic control and hyperglycemic rats. The extract at both doses significantly (P < 0.001) inhibited the spasmolytic activity in both normoglycemic and hyperglycemic rats compared to Imodium®. In rats DexIH rats, only dose 100 mg/kg significantly (P < 0.05) increased laxative effects when compared to the negative control. In vitro antiradical activity of GK revealed vitamin C-like antiradical activity.ConclusionsThis study justifies the traditional use of GK seeds as an antidiabetic.