Streptozotocin-induced Diabetic Wistar Rats Research Articles

Protective effect of Berberis asiatica root on biochemical and histopathological changes in streptozotocin-induced diabetic Wistar rats

Background: This study was designed to evaluate the effect of Berberis asiatica root extract (BAE) against streptozotocin induced elevated blood glucose level and other liver and kidney functions changes in adult male Wistar rats.Methods: Thirty male Wistar rats were divided into five groups of six rats in each (Groups I-V). Group I and Group II served as normal control and disease control, respectively. Group III received standard anti-diabetic drug glibenclamide (5mg/kg), while Group IV and Group V received the low dose (250mg/kg) and high dose (500mg/kg) of BAE. Serum blood glucose, SGOT, SGPT, ALP, total bilirubin, BUN, serum creatinine, TC, TG, HDL-C, LDL-C, and VLDL-C were estimated using standard methods. After collection of samples for biochemical evaluation, the pancreas from each animal was isolated and examined for histological changes.Results: BAE and glibenclamide treated disease rats showed significant (p <0.05) decrease in blood glucose concentration. Treatment with BAE at 250mg/kg and 500mg/kg in Group IV and V and standard drug glibenclamide in Group III showed significant (p <0.05) reduction in the level of liver function substances such as SGOT, SGPT, ALP and total bilirubin as compared to disease group, as well as showed significant (p <0.05) decrease in renal panel. Liver function parameters were significantly (p <0.05) improved in groups treated with BAE. Histopathological analysis revealed the protective effect of BAE against streptozotocin induced damage to islets of Langerhans.Conclusions: This study showed the destruction of islets of Langerhans and elevation in blood glucose level as well as alteration in other biochemical parameters were ameliorated by the effect of Berberis asiatica extract.

Modulatory effect of garcinol in streptozotocin-induced diabetic Wistar rats

The objective of the study was to evaluate the efficacy of garcinol as an antidiabetic candidate in streptozotocin-induced diabetic Wistar rats. Diabetic rats showed a significant increase in the biochemical parameters such as fasting blood glucose, glycated haemoglobin, urea, alanine aminotransferase and aspartate aminotransferase, malondialdehyde, total cholesterol, triglycerides, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, atherogenic index and a significant decrease in plasma insulin, HOMA-β-cell functioning index, glycogen, high-density lipoprotein cholesterol, body weight and antioxidant enzyme activities, viz. superoxide dismutase, catalase and reduced glutathione. Oral administration of garcinol (10 and 20 mg/kg body weight/day) for 30 days improved the above-mentioned alterations. The effect produced by the drug was compared with that of glibenclamide, a standard hypoglycaemic drug. These findings reveal that garcinol can be a promising antidiabetic candidate in the future.

Sapium ellipticum (Hochst) Pax ethanol leaf extract modulates glucokinase and glucose-6-phosphatase activities in streptozotocin induced diabetic rats

ObjectiveTo examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. MethodsSTZ-induced diabetic Wistar rats (four groups, n = 8) were used in this study. SE was assessed at two different doses, 400 and 800 mg/kg BW, in comparison with metformin (METF) (12 mg/kg BW) as a reference antidiabetic drug. All treatments were done orally (p.o), twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols. Hepatic and muscle glycogen contents were estimated as well. ResultsSTZ caused significant decrease in glucose-6-phosphatase activity and concomitant increase in glucokinase activity. SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals. However, the effects were significantly lower than that of METF which enhanced glucokinase activity by 94.76% and simultaneously inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. ConclusionsThe ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential.

Aqueous root extracts of Dicoma anomala (Sond.) extenuates postprandial hyperglycaemia in vitro and its modulation on the activities of carbohydrate-metabolizing enzymes in streptozotocin-induced diabetic Wistar rats

Dicoma anomala Sond (Asteraceae) is widely incorporated as a treatment for diabetes mellitus among the Basotho tribe of the Eastern Free State Province, South Africa. The study examined the antidiabetic effect of the plant via the in vitro inhibition of α-amylase, and α-glucosidase as well as against streptozotocin (STZ)-induced diabetic Wistar rats. The in vitro antidiabetic activity of the plant is via the inhibition of α-amylase, and α-glucosidase using water, ethanol, hydro-ethanol and methanol extracts. The effect of administration of aqueous root extract of Dicoma anomala (AQRED) at 125, 250, and 500mg/kg bodyweight (b.w.) on water consumption, feed intake, body-weight, blood glucose, carbohydrate-metabolizing enzymes, antioxidant enzymes, glycosylated haemoglobin and lipid profiles was determined in STZ (60mg/kg b.w.)-induced diabetic rats with comparison with glibenclamide (5mg/kg b.w.). While all the extracts of D. anomala showed activity against α-amylase and α-glucosidase, water extract revealed the most effective inhibition with an IC50 of 51.90 and 27.41μg/mL respectively. The water extract displayed competitive and non-competitive inhibitors of α-amylase and α-glucosidase respectively. AQRED reversed towards normal control the elevated food/water intake, blood glucose levels, lipid peroxidation, lipid profiles, glycosylated haemoglobin and activities of gluconeogenesis enzymes with a concomitant decrease in body-weight, activities of enzymatic antioxidants, glycolytic enzymes as well as the high-density lipoprotein-cholesterol level brought-about by STZ administration. The result of our findings proved the antihyperglycaemic activity of the plant and therefore validates the folkloric usage of the herb.

Sapium ellipticum (Hochst) Pax ethanol leaf extract modulates glucokinase and glucose-6–phosphatase activities in streptozotocin induced diabetic rats

Abstract Objective To examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. Methods STZ-induced diabetic Wistar rats (four groups, n = 8) were used in this study. SE was assessed at two different doses, 400 and 800 mg/kg BW, in comparison with metformin (METF) (12 mg/kg BW) as a reference antidiabetic drug. All treatments were done orally (p.o), twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols. Hepatic and muscle glycogen contents were estimated as well. Results STZ caused significant decrease in glucose-6-phosphatase activity and concomitant increase in glucokinase activity. SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals. However, the effects were significantly lower than that of METF which enhanced glucokinase activity by 94.76% and simultaneously inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. Conclusions The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential.

A sub-acute oral toxicity analysis and comparative in vivo anti-diabetic activity of zinc oxide, cerium oxide, silver nanoparticles, and Momordica charantia in streptozotocin-induced diabetic Wistar rats

Type 2 diabetes mellitus (T2DM) is one of the most threatening, non-communicable ailments worldwide.

In vitro and in vivo antidiabetic potential of extracts and a furostanol saponin from Balanites aegyptiaca

Context: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are well-known antidiabetic drug in Egyptian folk medicine. Nevertheless, its mechanism of action is still unclear.Objectives: Searching for the possible mechanisms of action of the plant and identification of its bioactive compounds.Materials and methods: A bio-guided protocol based on the evaluation of α‐glucosidase (AG) and aldose reductase (AR) inhibitory activities was adopted to isolate the biologically active compounds from the methanol extract (MeEx). An in vivo antidiabetic study was conducted for the active extract, fraction and compound using streptozotocin-induced diabetic male albino Wistar rats at two dose levels (100 and 200 mg/kg.b/wt) for 2 weeks.Results: Three compounds were isolated and identified: a sterol, (1) stigmasterol-3-O-β-d-glucopyranoside; a pregnane glucoside, (2) pregn-5-ene-3β,16β,20(R)-trio1-3-O-β-d-glucopyranoside; a furostanol saponin, (3) 26-(O-β-d-glucopyranosyl)-22-O-methylfurost-5-ene-3β,26-diol-3-O-β-d-glucopyranosyl-(1 → 4)-[α-l-rhamnopyranosyl-(1 → 2)]-β-d-glucopyranoside. Only compound 3 possessed significant AG and AR inhibitory activities (IC50 = 3.12 ± 0.17 and 1.04 ± 0.02 μg/mL, respectively), while compounds 1 and 2 were inactive. The in vivo antidiabetic study revealed that MeEx and furostanol saponin 3 possessed significant activities at a dose of 200 mg/kg through reducing the fasting plasma glucose level by 46.14% and 51.39%, respectively, as well as reducing the total cholesterol by 24.44% and 31.90%, respectively. Compound 3 also caused increment in insulin and C-peptide levels by 63.56% and 65%, respectively.Discussion and conclusions: We presented a scientific base for using Balanites aegyptiaca, and shed the light on one of its saponins, as an antidiabetic agent in fasting and postprandial hyperglycaemia along with the improvement of diabetic complications.

Evaluation of the neurobehavioural and Histo-architecture changes of the hippocampus and pancreas of the streptozotocin-induced diabetic male wistar rats responding to Z. Officinale extract

Evaluation of the neurobehavioural and Histo-architecture changes of the hippocampus and pancreas of the streptozotocin-induced diabetic male wistar rats responding to Z. Officinale extract

Anti-inflammatory effects of tyrosol in streptozotocin-induced diabetic Wistar rats

The anti-inflammatory effect of tyrosol (4-(2-hydroxyethyl)), a phenolic compound in olive oil (20 mg/kg body weight), in streptozotocin (STZ)-induced diabetic rat was evaluated. Diabetic rats showed significant (P < 0.05) increase in plasma glucose and lipid peroxidation products and significant (P < 0.05) decrease in plasma insulin and enzymatic and non-enzymatic antioxidants in the liver and pancreas. The levels of inflammatory marker, C-reactive protein in plasma and protein expressions of nuclear factor-kappa B p65, tumour necrosis factor-alpha and interleukin-6 in the liver and pancreas were significantly (P < 0.05) increased in STZ-induced diabetic rats. Conversely, daily oral treatment with tyrosol for 45 days significantly (P < 0.05) restored all the above mentioned parameters to near normal levels. The immunohistochemical studies confirm the anti-inflammatory effects of tyrosol. Tyrosol exerts anti-inflammatory effects on the liver and pancreas of STZ-induced diabetic rats via its antioxidant activity, hence it may play an important role in the management of diabetes mellitus.

Effects of Caffeine Administration on Brain Sodium-Potassium ATPase Activity in Healthy and Streptozotocin-Induced Diabetic Female Wistar Rats

Background: Diabetes mellitus affects the morphology and plasticity of the brain, leading to cognitive and electrophysiological impairment. We aim to determine effects of caffeine on brain Na+/K+-ATPase activity in streptozotocin-induced diabetic female rats. Methods: Female Wistar rats weighing about 180–200 g were used for the study and were divided into three study groups. Study groups A 1, 2, 3 were healthy rats administered 15, 20, 25 mg/kg caffeine intraperitoneally (i.p), respectively, for 5 weeks; study groups B 1, 2, 3 administered 15, 20, 25 mg/kg caffeine (i.p), respectively, for 5 weeks and maintained on caffeine for 3 weeks after diabetes induction; study groups C 1, 2, 3, were diabetic rats administered 15, 20, 25 mg/kg caffeine (i.p), respectively, for 3 weeks; control and diabetic untreated were administered normal saline. After administration, brains were homogenized in sucrose solution and kept at 4°C. Enzyme assay was conducted. Results: A significant (p < 0.05) decrease in Na+/K+-ATPas...

Effects of glycaemic variability on cardiac remodelling after reperfused myocardial infarction: Evaluation of streptozotocin-induced diabetic Wistar rats using cardiac magnetic resonance imaging

AimsIn addition to hyperglycaemia, glycaemic variability seems to be associated with poor outcomes after acute myocardial infarction. This study explored the impact of glycaemic variability in diabetic Wistar rats subjected to myocardial ischaemia/reperfusion. MethodsAnimals with streptozotocin-induced diabetes received insulin either to maintain stable hyperglycaemia (Dh group) or to generate glycaemic variability (Dv). After experimental myocardial ischaemia/reperfusion was surgically induced, 7T cardiac magnetic resonance imaging (CMR) was performed at weeks 1 (w1) and 3 (w3). ResultsTwenty-six rats were randomized [sham group (S): n=5; control group (C): n=7; Dh group: n=6; and Dv group: n=8]. The mean amplitude of glucose reflecting glycaemic variability was higher in the Dv than in the Dh group (9.1±2.7mmol/L vs 5.9±1.9mmol/L; P<0.05). CMR assessment at w3 revealed ventricular enlargement in both Dh and Dv groups compared with the C and S groups (end-diastolic volume: 1.60±0.22 and 1.36±0.30mL/kg compared with 1.11±0.13 and 0.87±0.11mL/kg, respectively; P<0.05). Circumferential strain was altered between w1 and w3 in the remote area only in the Dv group, resulting in a lower value in this group than in the S, C and Dh groups (−0.11±0.01 vs −0.17±0.05, −0.15±0.03 and −0.16±0.03, respectively; P<0.05). In addition, at w3, oedema was also higher in the remote area in the Dv than in the C group (18.3±4.9ms vs 14.5±1.7ms, respectively; P<0.05). ConclusionIn the context of experimental myocardial ischaemia/reperfusion, our results suggest that glycaemic variability might have a potentially deleterious impact on myocardial outcomes beyond the classical glucose metrics.

Antihyperglycemic and antidiabetic effects of Ethyl (S)-2-(1-cyclohexylsulfamide carbamoyloxy) propanoate in streptozotocin-induced diabetic Wistar rats

In this study, we examined the antihyperglycemic and antidiabetic effects of a novel synthesized molecule, the Ethyl (S)-2-(1-cyclohexylsulfamide carbamoyloxy) propanoate (ESP1b), in streptozotocin (STZ)-induced diabetic Wistar rats. Experimental diabetes mellitus was produced by a single intraperitoneal injection of STZ (55mg/kg b.w.). Seven day post-injection, animals have received ESP1b orally at the doses of 5, 10 and 20mg/kg b.w. daily for 28 days. This resulted in a clear decline, in a dose dependent manner, of blood glucose levels during the oral glucose tolerance test (OGTT) and the four weeks of treatment period. ESP1b at 20mg/kg b.w. has alleviated body weight loss, improved plasma insulin concentration and at the same time markedly decreased the values of glycosylated hemoglobin, lipoproteins and atherogenic ratios. Additionally, ESP1b notably restored renal as well as hepatic functions tests. Histopathological examinations of pancreatic tissue also confirmed the previous biochemical findings. Considering the obtained results, it may be concluded that ESP1b possess a potent antihyperglycemic activity in STZ-diabetic rats possibly related to an insulin-secretagogue effect, which may be responsible for the moderate decrease in blood glucose concentration observed in normal rats administrated with this tested compound.

The antioxidant effect of mulberry and jamun fruit wines by ameliorating oxidative stress in streptozotocin-induced diabetic Wistar rats.

Polyphenols act by scavenging reactive oxygen species during oxidative stress and hence are useful in the treatment of metabolic disorders including diabetes. This study describes the effect of polyphenol rich mulberry and jamun wines fed to streptozotocin-induced diabetic rats. To male adult Wistar rats, divided into groups (n = 10 per group) intraperitoneal injection was administered with streptozotocin at 38 mg per kg body weight for inducing diabetes. After confirmation of diabetes, rats divided into groups were fed each day with 5.7 milliliter per kg body weight of mulberry, jamun, white and red grape wines for 6 weeks. One group of animals received resveratrol at 20 mg per kg body weight. After six weeks of treatment, blood glucose, urinary profile, lipid profile, plasma, liver, kidney, brain and eye antioxidant enzyme activities, lipid peroxidation, non-esterified fatty acids (NEFA) and hepatic glutathione (GSH) content were determined. Though wine and resveratrol feeding did not improve the glycemic status of diabetic rats, increases in antioxidant enzymes and GSH content accompanied by reduced NEFA and lipid peroxidation were observed. The kidneys and brains of resveratrol fed rats showed significant reduction in malondialdehyde equivalents, exhibited an improved antioxidant status of tissues and an increased glutathione content. The findings suggested that the wines can ameliorate the consequences of diabetes due to their antioxidants.

CHRONIC CAFFEINE'S EFFECTS ON BEHAVIOURAL CHANGES IN STREPTOZOTOCIN-INDUCED DIABETIC RATS.

Memory deficits, anxiety and depression are often associated with diabetes, worsening diabetic patients' prognosis. Caffeine, a worldwide used psychoactive substance, is a candidate for improving these conditions. The aim of this study was to assess the behaviour in streptozotocin-induced diabetic Wistar rats and to evaluate the behavioural effects of caffeine administration. Diabetes was induced by a single intraperitoneal injection of 50 mg/kg BW streptozotocin (n=10), while control rats received the vehicle (n=9). After six weeks, behavioural tests for anxiety, memory and depression were performed: elevated plus maze (EPM) test, novel object recognition (NOR) test and forced swimming test (FST), respectively. The tests were repeated after further 2 weeks of continuous caffeine administration (20 mg/kg BW/day in drinking water). Diabetic rats manifested a high anxiety level, showed by a reduced exploratory activity compared to control rats (p<0.05) and long-term memory impairment, spending more time near the old object in NOR test. Caffeine administered for 2 weeks did not modify glycemic values in either group, and attenuated the behavioural changes observed in the EPM test. Also, in NOR test for long-term memory, caffeine administration induced an increased time spent with the novel object than with the old one in both groups. Our data suggest that chronic caffeine administration has an anxiolytic effect in diabetic rats and improves long-term memory in both diabetic and control rats.

Evaluation of the Antidiabetic Properties of Hydro-Alcoholic Extract and Its Fractions from &amp;lt;i&amp;gt;Physalis peruviana&amp;lt;/i&amp;gt; L. Leaves on Streptozotocin-Induced Diabetic Wistar Rats

The purpose of this study was to investigate the antidiabetic activity of extracts from leaves of <i>Physalis peruviana</i> L. used in the Eastern part of the Democratic Republic of the Congo used against diabetes. Different fractions with hexane, ethyl acetate and residue were obtained from the hydroalcoholic extract of <i>Physalis peruviana</i> leaves. The antidiabetic evaluation of hydroalcoholic and its fractions was evaluated in diabetic rats by a single administration of streptozotocin (50 mg/kg body weight) intravenously. The Reference group received glibenclamide (6.5 mg/kg body weight) and each test group received 100 mg/kg of body weight. Those groups were compared with a control group which received only a Tween 20 solution (1 ml per 100 g body weight). Serum biochemical profiles were evaluated by some blood markers including serum glucose, serum alanine transaminase (ALT), serum aspartate transaminase (AST) serum creatinine, total protein, triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol. Antidiabetic profile evaluation showed no significant variation (P &lt; 0.05) in blood glucose between groups after 28 days of treatment. There was no significant difference in the biochemical markers change including creatinine, ALT, AST, total protein, triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol. The hydroalcoholic extract from the leaves of <i>Physalis peruviana</i> L. and its fractions showed antidiabetic activity suggesting future detailed studies for new chemical entities lead drug discovery.

Hypoxis hemerocallidea Significantly Reduced Hyperglycaemia and Hyperglycaemic-Induced Oxidative Stress in the Liver and Kidney Tissues of Streptozotocin-Induced Diabetic Male Wistar Rats.

Background. Hypoxis hemerocallidea is a native plant that grows in the Southern African regions and is well known for its beneficial medicinal effects in the treatment of diabetes, cancer, and high blood pressure. Aim. This study evaluated the effects of Hypoxis hemerocallidea on oxidative stress biomarkers, hepatic injury, and other selected biomarkers in the liver and kidneys of healthy nondiabetic and streptozotocin- (STZ-) induced diabetic male Wistar rats. Materials and Methods. Rats were injected intraperitoneally with 50 mg/kg of STZ to induce diabetes. The plant extract-Hypoxis hemerocallidea (200 mg/kg or 800 mg/kg) aqueous solution was administered (daily) orally for 6 weeks. Antioxidant activities were analysed using a Multiskan Spectrum plate reader while other serum biomarkers were measured using the RANDOX chemistry analyser. Results. Both dosages (200 mg/kg and 800 mg/kg) of Hypoxis hemerocallidea significantly reduced the blood glucose levels in STZ-induced diabetic groups. Activities of liver enzymes were increased in the diabetic control and in the diabetic group treated with 800 mg/kg, whereas the 200 mg/kg dosage ameliorated hepatic injury. In the hepatic tissue, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), catalase, and total glutathione were reduced in the diabetic control group. However treatment with both doses improved the antioxidant status. The FRAP and the catalase activities in the kidney were elevated in the STZ-induced diabetic group treated with 800 mg/kg of the extract possibly due to compensatory responses. Conclusion. Hypoxis hemerocallidea demonstrated antihyperglycemic and antioxidant effects especially in the liver tissue.

The Effects of the Wild African Potato (Hypoxis hemerocallidea) Supplementation on Streptozotocin-Induced Diabetic Wistar Rats Reproductive Function

Sixty adult male Wistar rats (230-260 g) were randomly divided into 5 equal groups: normal, diabetic, diabetic +800 mg/kg H. hemerocallidea diabetes+200 mg/kg H. hemerocallidea and non-diabetic+800 mg/kg H. hemerocallidea. Diabetes was induced with a single intraperitoneal injection of 50 mg/kg streptozotocin (STZ) and monitored during the study period. Blood glucose levels showed a significant increase (5.117 ± 0.2412 vs. 30.70 ± 1.2630; p<0.05) 3 days after diabetes was induced using STZ. No mortality was observed during the study period. Blood samples, testes and epididymis were collected on the day of sacrifice. Testicular and epididymal lipid peroxidation (LPO) also showed a significant increase when diabetic control was compared to normal control. Body weights (315.7 ± 9.348 (g) vs. 210.2 ± 6.256 (g); p<0.05), epididymis (1.005 ± 0.0415 (g) vs. 0.7557 ± 0.0279 (g); p<0.05) and testicular (2.995 ± 0.1179 (g) versus 2.140 ± 0.0911 (g); p<0.05) weights, sperm motility and morphology, superoxide dismutase, catalase, total glutathione, total antioxidant capacity, testosterone and estradiol levels (p<0.05) decreased in the diabetic Wistar rats. After 6 week administration of H.hemerocallidea there was a significant improvement in the above parameters in diabetic Wistar rats (p<0.05). In addition, the non-diabetic +800 mg/kg H.hemerocallidea group showed improvement in some sperm motility parameters, epididymal GSHt, testosterone and estradiol levels when compared to the normal control group (p<0.05).These results indicated that H.hemerocallidea supplementation is an effective approach to ameliorate male infertility in diabetic rats.

Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus.

Emerging evidence suggests a selective up-regulation of arginase I in diabetes causing coronary artery disease; however, the mechanisms behind this up-regulation are still unknown. Activated p38 MAPK has been reported to increase arginase II in various cardiovascular diseases. We therefore tested the role of p38 MAPK in the regulation of arginase I and II expression and its effect on endothelial dysfunction in diabetes mellitus. Endothelial function was determined in septal coronary (SCA), left anterior descending coronary (LAD) and mesenteric (MA) arteries from healthy and streptozotocin-induced diabetic Wistar rats by wire myographs. Arginase activity and protein levels of arginase I, II, phospho-p38 MAPK and phospho-endothelial NOS (eNOS) (Ser(1177) ) were determined in these arteries from diabetic and healthy rats treated with a p38 MAPK inhibitor in vivo. Diabetic SCA and MA displayed impaired endothelium-dependent relaxation, which was prevented by arginase and p38 MAPK inhibition while LAD relaxation was not affected. Arginase I, phospho-p38 MAPK and eNOS protein expression was increased in diabetic coronary arteries. In diabetic MA, however, increased expression of arginase II and phospho-p38 MAPK, increased arginase activity and decreased expression of eNOS were observed. All these effects were reversed by p38 MAPK inhibition. Diabetes-induced activation of p38 MAPK causes endothelial dysfunction via selective up-regulation of arginase I expression in coronary arteries and arginase II expression in MA. Therefore, regional differences appear to exist in the arginase isoforms contributing to endothelial dysfunction in type 1 diabetes mellitus.

Amelioration of chronic inflammation and oxidative stress indices in diabetic Wistar rats using methanol leaf extract of Bridelia micrantha (Hochst) Baill. (Euphorbiaceae).

Ethnopharmacological practitioners in Nigeria have used aqueous and ethanol extracts of Bridelia micrantha leaves to manage conditions associated with inflammation, and these include diabetes, chest pain, edema, arthritis and joint pains. This study aimed to evaluate the effects of methanol leaf extract of B. micrantha on chronic inflammation and oxidative stress which accompany diabetic conditions, in streptozotocin-induced diabetic Albino Wistar rats. The dried leaves were extracted by percolation in 80% methanol:water for 72 h after which the mixture was filtered using Whatman No. 1 (11 μm) filter papers. Acute toxicity studies were done using Wistar rats and given orally up to a dose of 2,000 mg/kg. The animals were monitored for 48 h. The experimental design involved five (5) groups of six (6) albino Wistar diabetic rats each. Groups A, B and C rats received 100, 200 and 400 mg/kg B. micrantha respectively while groups D (negative control) and E (positive control) rats received 10 mL/kg normal saline and 200 mg/kg acetylsalicylic acid (ASA) respectively by gastric gavage for 7 days. Two sterilized cotton pellets (10 mg each) were implanted subcutaneously into both sides of the dorsal area of each diabetic rat in all the groups. Post cotton pellet implantation, rats in three groups (A, B and C) were treated with 100, 200 and 400 mg/kg B. micrantha extract, while those in two groups (D and E) were treated with acetyl salicylic acid (ASA 200 mg/kg) and normal saline (10 mL/kg) respectively by gastric gavage for 7 days. Serum obtained from the animals on Day 8 of the cotton pellet test were used for malondialdehyde (MDA), catalase, superoxide dismutase (SOD) and glutathione (GSH) assays. The administration of the leaf extract up to a dose of 2,000 mg/kg to rats produced absolutely no death or observable signs of toxicity in 48 h. The cotton pellet granuloma weights in 200 mg/kg (44.88±1.2 mg), 400 mg/kg (42.10±1.2 mg) B. micrantha extract treated groups and ASA at 200 mg/kg (43.25±1.8 mg) were significantly lower compared to weight of granuloma (85.50±3.2 mg) obtained in the group treated with normal saline. Serum malondialdehyde (MDA) level in the 200 mg/kg (3.32±0.72 nmol/mL) and 400 mg/kg (1.88±1.27 nmol/mL) B. micrantha extract treated groups were significantly (p<0.05) lower compared to MDA level (6.88±0.79 nmol/mL) in the serum of normal saline treated group. Treatment of diabetic rats with the B. micrantha extract also caused significant (p<0.05) elevation in serum catalase, SOD and GSH levels. The study showed that B. micrantha methanol leaf extract significantly inhibited some chronic inflammation and oxidative stress parameters in diabetes mellitus.

In Vivo Anti-Hyperglycemic Potential of Brahmi Gritham and Docking Studies of Its Active Components Against Protein Kinase C and CD38

The anti-hyperglycemic and antioxidant effects of the Indian herbal formulation Brahmi gritham were studied in streptozotocin-induced diabetic female Wistar albino rats. Diabetes was induced by a single dose of streptozotocin (55 mg/kg body weight [b.w.], i.p.). Estimation of blood glucose levels, liver glycogen content and antioxidant levels were carried out in experimental rats. The tested parameters were compared with those of the glibenclamide (600 μg/kg b.w.) treated group. Molecular docking studies were carried out to analyze the interaction patterns of protein kinase C (PKC) and CD38 of chosen proteins of signal transduction pathways that are significant in the pathogenesis of diabetes against active components of Brahmi gritham. Immunohistochemistry of pancreas revealed that Brahmi gritham was able to restore β-cell mass and function near to that of the normal control. In silico studies showed that apigenin and quercetin showed significant interactions with PKC, while clitorin, bacopaside I and II showed significant interactions with CD38. Quercetin showed highest percentage inhibition of α-amylase enzyme. Practical Applications Brahmi gritham is a traditional polyherbal formulation used in Ayurveda to treat memory disorders. The individual components of this formulation are known to possess significant antioxidant properties and contain several biologically active compounds found to be effective in treating various disorders, including diabetes and obesity. The efficacy of Brahmi gritham in diabetes management has not yet been studied, and therefore, the present study provides insights into the anti-hyperglycemic potential of this formulation in rat model. In addition, the results of in silico analysis would pave way for better utilization of the flavonoids quercetin and apigenin in diabetes management and in particular microvascular diabetic complications.