Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic β-cells of streptozotocin-induced diabetic rats

Background: The present study investigated the effects of Nigella sativa aqueous extract and oil, as well as thymoquinone, on serum insulin and glucose concentrations in streptozotocin (STZ) diabetic rats. Methods: Rats were divided into five experimental groups (control, untreated STZ‐diabetic, and aqueous extract‐, oil‐, or thymoquinone‐treated diabetic rats). Treated rats received 2 mL/kg, i.p., 5%N. sativa extract, 0.2 mL/kg, i.p., N. sativa oil, or 3 mg/mL, i.p., thymoquinone 6 days/week for 30 days. Serum insulin and glucose concentrations, superoxide dismutase (SOD) levels, and pancreatic tissue malondialdehyde (MDA) were determined. Electron microscopy was used to identify any subcellular changes. Results: Diabetes increased tissue MDA and serum glucose levels and decreased insulin and SOD levels. Treatment of rats with N. sativa extract and oil, as well as thymoquinone, significantly decreased the diabetes‐induced increases in tissue MDA and serum glucose and significantly increased serum insulin and tissue SOD. Ultrastructurally, thymoquinone ameliorated most of the toxic effects of STZ, including segregated nucleoli, heterochromatin aggregates (indicating DNA damage), and mitochondrial vacuolization and fragmentation. The aqueous extract of N. sativa also reversed these effects of STZ, but to a lesser extent. The N. sativa oil restored normal insulin levels, but failed to decrease serum glucose concentrations to normal. Conclusions: The biochemical and ultrastructural findings suggest that N. sativa extract and thymoquinone have therapeutic and protect against STZ‐diabetes by decreasing oxidative stress, thus preserving pancreatic β‐cell integrity. The hypoglycemic effect observed could be due to amelioration of β‐cell ultrastructure, thus leading to increased insulin levels. Consequently, N. sativa and thymoquinone may prove clinically useful in the treatment of diabetics and in the protection of β‐cells against oxidative stress.     

Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia

Background: Oxidative stress, produced under diabetic conditions, may cause tissue damage. Although several drugs are currently available for the treatment of diabetes, their continued use may cause unwanted side effects. The aim of the present study was to evaluate the antioxidant potential of β‐sitosterol (BS), a phytosterol from Solanum surattense, using an experimental model for diabetes‐induced oxidative damage. Methods: The effects of 21 days treatment with BS (10, 15 and 20 mg/kg, p.o.) on blood, serum, and tissue biochemical parameters were evaluated in control and streptozotocin‐induced diabetic rats. Nine experimental groups, including a control group, a diabetic group, and BS‐ and glibenclamide‐treated diabetic groups, were evaluated. Results: All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels. Furthermore, treatment with BS doses also increased pancreatic antioxidant levels, with a concomitant decrease in thiobarbituric acid‐reactive substances. Conclusions: β‐Sitosterol has promising antidiabetic as well as antioxidant effects and may be considered in clinical studies for drug development.     

Antioxidant potential of zinc–flavonol complex studied in streptozotocin‐diabetic rats (锌黄酮醇复合物在链脲霉素‐糖尿病大鼠中的抗氧化作用)

Background: Diabetic oxidative stress coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Zinc is an essential trace element with significant antidiabetic activity. However, the acceptance of zinc compounds as promising therapeutic antidiabetic agents has been slowed due to concerns regarding chronic toxicity. Recently, we have designed, synthesized and characterized a novel zinc–flavonol complex and evaluated its antidiabetic efficacy in streptozotocin (STZ)‐diabetic rats. The aim of the present study was to evaluate the role of the zinc–flavonol complex in the antioxidant status of diabetic rats. Methods: Diabetes was induced in rats by i.p. injection of STZ. Diabetic rats were then treated with the zinc–flavonol complex (5 mg/kg, p.o.) for 30 days. The extent of oxidative stress was assessed by determining lipid peroxide levels, pancreatic tissue antioxidant enzyme activities and plasma concentrations of non‐enzymatic antioxidants. In addition, nuclear levels of nuclear factor (NF)‐κB p65, pancreatic nitric oxide (NO), and plasma levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β and IL‐6 were determined. Pancreatic tissues were examined histologically. Results: Oral treatment with the zinc–flavonol complex significantly improved antioxidant levels and alleviated levels of oxidative stress markers. Furthermore, significant increases were seen in NF‐κB p65, NO, TNF‐α, IL‐1β and IL‐6 levels. Histological observations revealed that the zinc–flavonol complex effectively protects pancreatic β‐cells against oxidative damage. Conclusion: The results of the present study indicate that the zinc–flavonol complex has an antioxidative and anti‐inflammatory role in the diabetic milieu.     

Antidiabetic activity of gossypin, a pentahydroxyflavone glucoside, in streptozotocin-induced experimental diabetes in rats

Background: Most of the currently available oral hypoglycemic drugs for the treatment of diabetes mellitus elicit detrimental side effects. Hence, the search for plant‐derived products for the treatment of diabetes continues. Gossypin, a pentahydroxy flavone glucoside found in the flowers of Hibiscus vitifolius, has many biological properties, including as an antioxidant, anti‐inflammatory and anticancer agent. The aim of the present study was to evaluate the effect of gossypin in streptozotocin (STZ)‐induced experimental diabetes in rats. Methods: Diabetic rats were administered 20 mg/kg per day gossypin orally for 30 days. On the 28th day, rats were subjected to an oral glucose tolerance test. In addition, blood glucose, plasma insulin, hemoglobin, and HbA1c levels were determined, as was the glycogen content of the liver and muscles. Plasma protein and blood urea were also estimated. Results: Oral administration of gossypin to diabetic rats resulted in improved glucose tolerance. Increased blood glucose and HbA1c levels and the reduced plasma insulin and hemoglobin levels in diabetic rats were significantly reversed to near normal after oral administration of gossypin. Furthermore, the glycogen content of the liver and muscles was significantly improved after gossypin treatment of diabetic rats, and plasma protein and blood urea levels were almost normalized. The data obtained in gossypin‐treated rats were comparable with those obtained following gliclazide treatment of rats, a standard reference drug for diabetes. Conclusions: The results of the present study indicate that gossypin has potent antidiabetic activity in STZ‐induced experimental diabetes in rats.     

Antioxidant activity and protection of pancreatic β-cells by embelin in streptozotocin-induced diabetes

Objectives: The aim of the present study was to evaluate the antioxidant potential of embelin in streptozotocin‐induced diabetes. Methods: Diabetes was induced in rats fasted overnight by the administration of a single dose of streptozotocin, and analyzed for blood, serum, and biological and histological pancreatic tissue parameters in intact control, diabetic, and embelin‐treated diabetic rats (n = 9) at the dose levels of 15, 25, and 30 mg/kg/day for 21 days. Results: Diabetes caused highly significant abnormalities in blood, serum, and pancreatic tissue biochemical parameters. Embelin and glibenclamide administration to diabetic rats caused a highly significant decline in the blood glycated hemoglobin and serum glucose levels and nitric oxide activity, with a concomitant increase in the serum insulin level (P < 0.001). Furthermore, embelin and glibenclamide treatment increased the pancreatic antioxidant enzyme status (superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione S‐transferase, and ascorbic acid), and also decreased the thiobarbituric acid reactive oxygen species contents (P < 0.001). The histoarchitecture of the diabetic rats typically showed a degenerated pancreas with reduced β‐cell counts, while embelin treatment was shown to significantly regenerate islet cells. Conclusion: The study proves the potent antioxidant activity of embelin, which has been found to be effective in managing severe hyperglycemia.     

Evaluation of antihyperglycemic and antioxidant properties of Streblus asper Lour against streptozotocin–induced diabetes in rats

ObjectiveTo evaluate antidiabetic and antioxidant role of methanol extract of Streblus asper (S. asper) root bark in Wistar rats.MethodsDiabetes was induced in rats by single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight). Three days after STZ induction, the diabetic rats were treated with S. asper orally at dose of 200 and 400 mg/kg body weight daily for 15 days. Glibenclamide (0.25 mg/kg, orally) was used as reference drug. The fasting blood glucose levels were measured on every fifth day during the 15-day treatment. Serum biochemical parameters such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, total cholesterol total protein and serum triglycerides were estimated. Antioxidant properties were assessed by estimating liver and kidney thiobarbituric acid reactive substances, reduced glutathione and catalase.ResultsS. asper in STZ-induced diabetic rats, at doses of 200 and 400 mg/kg bw produced reduction in blood glucose levels when compared with the STZ control group. Serum biochemical parameters antioxidant levels were significantly restored toward normal levels in S. asper treated rats as compared with STZ control.ConclusionsThe present study infers that the methanol extract of S. asper root bark demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats. The potential antidiabetic action is plausibly due to its underlying antioxidant role.     

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats

Background: Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long‐term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. Methods: The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan‐induced diabetic rats. The effects of these extracts were compared with the effect of 30‐days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Results: Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. Conclusion: The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development.     

Salutary Effect of <Emphasis Type="Italic">Cassia auriculata</Emphasis> L. Leaves on Hyperglycemia-Induced Atherosclerotic Environment in Streptozotocin Rats

Diabetes mellitus is very often associated with dyslipidemia, increased oxidative stress and endothelial dysfunction that could develop atherosclerosis and consequently cardiovascular diseases. Medicinal plants with reputed traditional use to treat diabetes and cardiovascular diseases might provide valuable drugs. Therefore, the present study was designed to evaluate anti-atherosclerotic potential of aqueous extract of Cassia auriculata L. leaves in streptozotocin (STZ)-induced diabetic rats. The rats were rendered diabetic by STZ (45 mg/kg, ip). Diabetic rats were orally administered C. auriculata leaf extract at 400 mg/kg dose daily for 21 days. The supplementation of extract to the diabetic rats produced significant reduction in fasting blood glucose along with significant reversal in altered serum lipid profile and apolipoprotein B. Lipid peroxidation was found to be significantly suppressed in extract-fed diabetic rats. The significant reduction in serum levels of oxidized low-density lipoprotein, soluble vascular cell adhesion molecule and plasma fibrinogen with a concomitant elevation in serum nitric oxide was observed in diabetic rats following treatment with extract. Histopathological examination of heart myocardium of extract-treated diabetic rats revealed reversal of fatty change toward normal. These results suggest that C. auriculata aqueous leaf extract exhibits anti-atherosclerotic role in the diabetic state and it indicates toward the notion that extract may help to prevent the progression of cardiovascular diseases.     

Antidiabetic, antihyperlipidemic and antioxidant potential of methanol extract of Tectona grandis flowers in streptozotocin induced diabetic rats

ObjectiveTo investigate antidiabetic, antihyperlipidemic and antioxidant activity of methanol extract of Tectona grandis (T. grandis) flowers (METGF) in streptozotocin (STZ) induced diabetic rats to supports its traditional use.MethodsAcute toxicity study of METGF was carried out in rat to determine its dose for the antidiabetic study. Oral glucose tolerance test (OGTT) was performed to evaluate METGF effect on elevated blood glucose level. Diabetes was induced in rats by administration of STZ (60 mg/kg, ip.) and it was confirmed 72 h after induction. METGF was orally given to the diabetic rats up to 28 days and blood glucose level were estimated each week. On 28 day of the experiment, diabetic rats were sacrificed after the blood collection for the biochemical parameters analysis and liver, kidney was collected to determine antioxidants levels.ResultsIn acute toxicity, METGF did not show toxicity and death up to a dose 2 000 mg/kg in rats. Administration of METGF 100 and 200 mg/kg significantly (P<0.001) reduced blood glucose levels in OGTT and STZ-induced diabetic rats. Both doses of METGF treatment significantly (P<0.001, P<0.01 and P<0.05) increased body weight, serum insulin, haemoglobin (Hb) and total protein levels in diabetic rats. Also, MEGTF treatment reduced elevated glycosylated haemoglobin (HbA1c) and other biochemical parameters levels significantly (P<0.001) in diabetic rats. Altered lipid profiles and antioxidants levels were reversed to near normal in diabetic rats treated with METGF.ConclusionsThese results concluded that METGF possesses antidiabetic, antihyperglycemic and antioxidant activity which supports its traditional use.     

The antidiabetic effect of Geigeria alata is mediated by enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant activity in streptozotocin-induced diabetic rats

In Sudanese folk medicine, Geigeria alata roots have been used for the management of diabetes for a long time. However, its antidiabetic activity is unreported. In this study, G. alata methanolic extract was tested for its antidiabetic, antioxidant, and β-cell modulatory effects in a streptozotocin-induced diabetic rat model. In this model of diabetic rats, the oral glucose tolerance test with G. alata extract at 125, 250, and 500?mg/kg doses revealed the efficacy of the 250?mg/kg dose in improving glucose tolerance comparable to the standard drug glibenclamide. Diabetic rats were treated with a 250?mg/kg dose of G. alata extract orally for 2?h (acute) or 14 days (chronic). In the case of acute treatment, the extract lowered blood glucose levels significantly at 120?min both in nondiabetic and diabetic rats. Chronic treatment of diabetic rats with 250?mg/kg of G. alata extract resulted in a significant decrease in blood glucose level closer to that of nondiabetic rats. Interestingly, increased serum insulin, improved β-cell function, and antioxidant status were observed in G. alata-treated diabetic rats. G. alata also showed strong antioxidant and α-glucosidase inhibitory activities in in vitro assays. These data show direct evidence that G. alata has antidiabetic activity and suggest that the antidiabetic activity is due to enhanced insulin secretion, modulation of β-cell function, and improvement of antioxidant status.     

Modulation of methylglyoxal and glutathione by soybean isoflavones in mild streptozotocin-induced diabetic rats

Background and aimsEvidence shows that methylglyoxal (MG), a very reactive metabolite of glucose, plays a critical role in the pathogenesis of diabetes and diabetic complications. Although soy isoflavones have beneficial effects in diabetes, the role of soy isoflavones in regulating MG levels is unknown. The present study investigates the effects of soy protein isoflavones on MG and reduced glutathione (GSH).Methods and resultsMild diabetes was induced in male Sprague-Dawley rats by intraperitoneal injection of 35 mg/kg streptozotocin (STZ). The diabetic rats were then randomly divided into three groups and received a special diet supplemented with casein (control), low-isoflavone soy protein (LIS), or high-isoflavone soy protein (HIS) for eight weeks, respectively. Compared to the control or LIS group, HIS diet significantly increased serum insulin levels (p < 0.01 or 0.05) and reduced serum glucose and MG levels (p < 0.05). Serum GSH levels were increased in HIS-fed rats compared with the control or LIS group (p < 0.01). Serum total cholesterol and homocysteine levels were significantly lower in HIS and LIS rats than those of the control rats.ConclusionsBoth LIS and HIS diets can lower serum lipid and homocysteine levels in this mild diabetic model. HIS diet enhances insulin secretion and reduces glucose level. Moreover, the HIS diet has potential in reducing MG and increasing GSH levels. In addition to its hypoglycemic effect, the antioxidant protection may provide beneficial effects in preventing the development of diabetic complications.     

Antidiabetic and antihypertensive effect of a polyphenol-rich fraction of Thymelaea hirsuta L. in a model of neonatal streptozotocin-diabetic and N(G) -nitro-l-arginine methyl ester-hypertensive rats

Background: The present study examined the effect of the polyphenol‐rich fraction from Thymelaea hirsuta (PRF‐Th) in a rat model of streptozotocin (STZ)‐diabetes and nitric oxide (NO)‐deficient hypertension. Methods: Diabetes was induced by a single dose of STZ (90 mg/kg, i.p.). To induce NO‐deficient hypertension, rats were treated with the NO synthase inhibitor N^G‐nitro‐l ‐arginine methyl ester; l ‐NAME; 30 mg/kg per day, p.o. for 3 weeks. The effects of 21 days treatment with 80 mg/kg per day PRF‐Th in the drinking water were evaluated in diabetic–hypertensive (DH) rats. In all groups (n = 6 in each), glycemia and systolic blood pressure were determined weekly. At the end of the experiment, hepatic glycogen was determined. Results: Blood glucose levels decreased gradually from baseline until the end of the experiment in untreated DH rats (from 1.92 ± 0.09 to 1.3 ± 0.1 g/L; P < 0.05). Administration of PRF‐Th concomitantly with l ‐NAME prevented the blood pressure increase in rats. After 21 days, blood pressure in PRF‐Th + l ‐NAME‐ and l ‐NAME‐treated rats was 132 ± 1 and 157 ± 1 mmHg, respectively (P < 0.001). Administration of 2 mL/kg per day PRF‐Th to DH rats significantly increased hepatic glycogen levels compared with levels in untreated DH rats (13.65 ± 1.84 vs 6.34 ± 0.75 mg/g tissue, respectively; P < 0.01). Moreover, PRF‐Th significantly reduced the amount of glucose absorbed in in situ perfused jejunum segments compared with control (by 33.6%; P < 0.001). This effect of PRF‐Th was comparable with that of acarbose, an α‐glucosidase inhibitor. Conclusions: The findings of the present study indicate that T. hirsuta has antidiabetic and antihypertensive activity in STZ‐diabetic, NO‐deficient hypertensive rats. This effect seems to be due to its rich polyphenol content. Therefore, T. hirsuta may be useful as a food supplement for the prevention of type 2 diabetes and hypertension.     

Minocycline completely reverses mechanical hyperalgesia in diabetic rats through microglia-induced changes in the expression of the potassium chloride co-transporter 2 (KCC2) at the spinal cord

Aim: Neuronal hyperactivity at the spinal cord during mechanical hyperalgesia induced by diabetes may result from a decrease in the local expression of the potassium chloride co‐transporter 2 (KCC2), which shifts the action of the neurotransmitter γ‐amminobutiric acid (GABA) from inhibitory to excitatory. In this study, we evaluated the effects of spinal microglia inhibition or brain‐derived neurotrophic factor (BDNF) blockade on KCC2 expression, spinal neuronal activity and mechanically induced pain responses of streptozotocin (STZ)‐diabetic rats. Methods: Four weeks after induction of diabetes, the STZ‐diabetic rats received daily intrathecal injections, for 3 days, of minocycline (microglia inhibitor), TrkB/Fc (BDNF sequester) or saline. Behavioural responses to mechanical nociceptive stimulation of STZ‐diabetic rats were evaluated by the Randall‐Selitto test. The lumbar spinal cord was immunoreacted against the Fos protein (marker of neuronal activation) or KCC2, which was also quantified by western blotting. BDNF levels at the spinal cord were quantified by an enzyme‐linked immunosorbent assay (ELISA). Results: Minocycline treatment reversed the mechanical hyperalgesia, increased Fos expression and decreased the KCC2 expression detected in STZ‐diabetic rats to control levels. Treatment with TrkB/Fc was less effective, inducing moderate effects in mechanical hyperalgesia and Fos expression and only a partial correction of KCC2 expression. BDNF levels were not increased in STZ‐diabetic rats. Conclusions: This study demonstrates that the microglial activation at the spinal cord contributes to mechanical hyperalgesia and spinal neuronal hyperactivity induced by diabetes, apparently by regulating the KCC2 expression. These effects do not seem to be mediated by BDNF, which is an important difference from other chronic pain conditions. New targets directed to prevent spinal microglia activation should be considered for the treatment of mechanical hyperalgesia induced by diabetes.     

<Emphasis Type="Italic">Moringa oleifera</Emphasis> supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose

There are strong correlations between diabetes mellitus and cognitive dysfunction. This study sought to investigate the modulatory effects of Moringa oleifera leaf (ML) and seed (MS) inclusive diets on biomolecules [acetylcholinesterase (AChE), butyrylcholinesterase (BChE)] angiotensin-I converting enzyme (ACE), arginase, catalase, glutathione transferase (GST) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and nitric oxide (NO) levels] associated with cognitive function in the brain of streptozotocin (STZ)-induced diabetic rats treated with acarbose (ACA). The rats were made diabetic by intraperitoneal administration of 0.1 M sodium-citrate buffer (pH 4.5) containing STZ [60 mg/kg b.w (BW)] and fed with diets containing 2 and 4% ML/MS. Acarbose (25 mg/kg BW) was administered by gavage daily for 14 days. The animals were distributed in eleven groups of eight animals as follows: control, STZ-induced, STZ?+?ACA, STZ?+?2% ML, STZ?+?ACA?+?2% ML, STZ?+?4% ML, STZ?+?ACA?+?4% ML, STZ?+?2% MS, STZ?+?ACA?+?2% MS, STZ?+?4% MS, STZ?+?ACA?+?4% MS. There were marked increase in AChE, BChE, arginase, ACE and concomitant decrease in catalase, GST, GSH-Px, activities and NO levels in STZ-diabetic group compared with the control. However, there was a decrease in AChE, BChE and ACE activities and concomitant increase in the antioxidant molecules in the groups fed with supplemented diets treated with/without ACA compared with the STZ-diabetic group. These findings suggest that ML/MS supplemented diet could prevent cognitive dysfunction-induced by chronic hyperglycemia.     

Emblica officinalis improves glycemic status and oxidative stress in STZ induced type 2 diabetic model rats

Objective:To evaluate the antidiabetic and antioxidant potential of Emblica officinalis(E.officinalis)fruit on normal and type 2 diabetic rats.Methods:Type 2 diabetes was induced into the male Long-Evans rats.The rats were divided into nine groups including control groups receiving water,type 2 diabetic controls,type 2 diabetic rats treated with glibenclamide(T2GT)and type 2diabetic rats treated with aqueous extract of fruit pulp of E.officinalis.They were fed orally for8 weeks with a single feeding.Blood was collected by cutting the tail tip on 0 and 28 days and by decapitation on 56 day.Packed red blood cells and serum were used for evaluating different biochemical parameters.Results:Four weeks administration of aqueous extract of E.officinalis improved oral glucose tolerance in type 2 rats and after 8 weeks it caused significant(P0.007)reduction in fasting serum glucose level compared to 0 day.Triglycerides decreased by 14%but there was no significant change in serum ALT,creatinine,cholesterol and insulin level in any group.Furthermore,reduced erythrocyte malondialdehyde level showed no significant change(P0.07)but reduced glutathione content was found to be increased significantly(P0.05).Conclusions:The aqueous extract of E.officinalis has a promising antidiabetic and antioxidant properties and may be considered for further clinical studies in drug development.     

Antidiabetic and antioxidant activities of Nypa fruticans Wurmb. vinegar sample from Malaysia

Objective: To study the antidiabetic and antioxidant activities of nipa palm vinegar(NPV) used in traditional Malay medicine for treating diabetes. Methods: NPV was extracted using liquid-liquid extraction method and the obtained samples were subjected to antidiabetic studies using normal and streptozotocin-induced diabetic rat models whereas antidoxidant activities were investigated via in vitro antioxidant tests namely 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radicals scavenging activities and the reducing power assay. Results: Single administration of NPV and its extracts were not effective in both normal and diabetic rats. In intraperitoneal glucose tolerance test, NPV and its aqueous extract showed significant blood glucose lowering effect. In the sub-acute study, compared with the diabetic control, aqueous extract of NPV showed the most notable blood glucose lowering effect(56.6%) and a significant improvement in serum insulin levels(79.8%, P0.05). To assess NPV's antioxidant activity, three in vitro antioxidant tests were employed: 2,2-diphenyl-1-picryhydrazyl and 2,2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid free radical-scavenging assays, and the reducing power assay. Ethyl acetate extract had the greatest antioxidant potential and content of phenolic and flavonoid compounds. A linear positive correlation between the antioxidant parameters was observed. Chemical profiling analysis of aqueous extract of NPV revealed the presence of acetic acid(35.25%), the main active constituent which significantly contributed to the observed antidiabetic activity. Conclusions: Aqueous extract of NPV possesses antihyperglycaemic activities comparable to the metformin, while the ethyl acetate extract precipitated significant antioxidant effects attributable to its high phenolic content. These findings suggest that antioxidant compounds of NPV do not contribute much towards the overall observed antidiabetic effect.     

Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats

Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). The present study was hypothesized to investigate the beneficial effects of hesperidin and naringin on hyperglycemia-induced oxidative damage in HFD/STZ-induced diabetic rats. Diabetes was induced by feeding rats with an HFD for 2 weeks followed by an intraperitoneal injection of STZ (35 mg/kg body weight). An oral dose of 50 mg/kg hesperidin or naringin was daily given for 4 weeks after diabetes induction. At the end of the experimental period, blood was obtained from jugular vein and livers were rapidly excised and homogenized for biochemical assays. In the diabetic control group, levels of glucose, glycosylated hemoglobin (HbA1c%), MDA, NO, TNF-α and IL-6 were significantly increased, while serum insulin, GSH, vitamin C, and vitamin E levels were decreased. Both hesperidin and naringin administration significantly reversed these alterations. Moreover, supplementation with either compound significantly ameliorated serum and liver MDA, NO and glutathione, and liver antioxidant enzymes. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of hesperidin and naringin against diabetic complications, these preliminary experimental findings demonstrate that both hesperidin and naringin exhibit antidiabetic effects in a rat model of T2DM by potentiating the antioxidant defense system and suppressing proinflammatory cytokine production.     

Effects of Gmelina arborea extract on experimentally induced diabetes

ObjectiveTo study the effects of aqueous extract of Gmelina arborea bark on normoglycemic levels and streptozotocin (STZ) induced diabetes in rats.MethodsAfter single administration of the aqueous extract, plasma glucose level was determined up to 6 h. In subacute study, the aqueous extract was administered for 28 d and plasma glucose level was determined weekly. The diabetes was induced in rats by the intraperitoneal injection of STZ at a dose of 55 mg/kg body weight. The diabetic animals were divided into four groups containing six in each: Group I diabetic control, Group II and III treated with the aqueous extract respectively at a dose of 250 and 500 mg/kg body weight once daily and Group IV treated with glibenclamide at a dose of 0.6 mg/kg body weight once daily. In acute study, the aqueous extract and glibenclamide were administered orally to rats. Plasma glucose levels were determined at 30, 60, 120, 240 and 360 min after the administration of the test samples. To study subacute effects, test samples (the aqueous extract and glibenclamide) were administered for 28 d consecutively. The effects of each test sample on plasma glucose level, body weight as well as food and water intake were also monitored weekly. The oral glucose tolerance test and biochemical indicators were estimated on day 28.ResultsThe aqueous extract did not significantly decrease the plasma glucose level in the normoglycemic rats as shown by the acute and subacute assays. However, after oral administration of the aqueous extract, the plasma glucose level was significantly (P<0.001) decreased in the diabetic rats in the acute study. The long-term administration of the aqueous extract significantly (P<0.001) reduced plasma glucose levels of the diabetic rats. Additionally, the aqueous extract also reduced loss of body weight and significantly decreased food and water intake in the diabetic animals. Nevertheless, no effects on biochemical indicators were observed at the selected doses.ConclusionsThe aqueous extract of Gmelina arborea bark had antihyperglycemic activity against STZ induced diabetes in rats, after single and subacute oral administration. Moreover, it did not show significant glucose lowering effect in normoglycemic rats.     

Hypoglycemic activity of Hemidesmus indicus R. Br. on streptozotocin-induced diabetic rats

OBJECTIVE:

To evaluate the antidiabetic activity of an aqueous extract of the roots of Hemidesmus indicus on blood glucose, serum electrolytes, serum marker enzymes, liver microsomal P-450 enzymes, and lipid peroxidation in the liver and kidney of streptozotocin-induced diabetic rats.

MATERIALS AND METHODS:

Effect of H. indicus extract on blood glucose was studied with fed, fasted and glucose-loaded diabetic and nondiabetic rat models. The effect of the extract on serum electrolytes, serum levels of key glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems and lipid peroxidation in the liver and kidney of diabetic rats. One way analysis of variance and Duncan''s multiple range test was used for statistical analysis.

RESULTS:

Oral administration of H. indicus aqueous extract to fed, fasted and glucose-loaded diabetic rats decreased blood glucose level significantly at 5 h and restored serum electrolytes, glycolytic enzymes and hepatic cytochrome P-450-dependent enzyme systems by preventing the formation of liver and kidney lipid peroxides at the end of 12 weeks of the study period.

CONCLUSION:

From the studies, it can be concluded that the aqueous extract of the roots of H. indicus at a dosage of 500 mg/kg/day exhibits significant antidiabetic activity. It restores the concentrations of electrolytes, glucose metabolizing enzymes, hepatic microsomal protein and hepatic cytochrome P-450-dependent mono-oxygenase enzyme systems to near normal level and also corrects the related metabolic alterations in experimentally induced diabetic rats. H. indicus administration also decreased liver and kidney lipid peroxidation products. On the basis of our findings, H. indicus could be used as an antidiabetic and antioxidant agent for the prevention and treatment of diabetes mellitus.     

Antidiabetic, hypolipidemic and histopathological analysis of Dillenia indica (L.) leaves extract on alloxan induced diabetic rats

ObjectiveTo investigate antidiabetic, hypolipidemic histopathological analysis of Dillenia indica (D. indica) methanolic leaves (DIME) extract in alloxan induced diabetic rat by administering oral doses (250 and 500 mg/kg body weight).MethodsBlood glucose levels were measured using blood glucose test strips with elegance glucometer on weekly intervals till the end of study (i.e. 3 weeks). Other parameters e.g. liver profile, renal profile and total lipid levels were determined in normal and alloxan induced diabetic rats after oral administration of the extract for 21 days. Histopathological changes in diabetic rat organs (pancreas, liver and kidney) were also observed after extract treatment.ResultsDaily oral administration DIME (250 and 500 mg/kg body weight) and glibenclamide (10 mg/kg) showed beneficial effects on blood glucose level (P < 0.001) as well as improving kidney, liver functions and hyperlipidaemia due to diabetes. The extract treatment also showed to enhanced serum insulin level and body weight of diabetic rats as compared to diabetic control group. Furthermore, the extract has a favorable effect on the histopathological changes of the pancreas, liver and kidney in alloxan induced diabetes.ConclusionsD. indica possess antidiabetic property as well improve body weight, liver profile, renal profile and total lipid levels. DIME has also favorable effect to inhibit the histopathological changes of the pancreas and kidney in alloxan induced diabetes.