Antihyperlipidaemic Effect of Gymnema montanum: A Study on Lipid Profile and Fatty Acid Composition in Experimental Diabetes

Abstract: In the present study, the antihyperlipidaemic efficacy of ethanol extract of Gymnema montanum leaves was investigated in alloxan‐induced diabetic rats and the effect was compared to standard hypoglycaemic drug, glibenclamide. Male adult albino Wistar rats were injected with freshly prepared solution of alloxan monohydrate (150 mg/kg body weight) to induce diabetes. After 2 weeks, the rats with moderate diabetes were administered G. montanum leaves (200 mg/kg body weight) for 21 days by gastric lavage, after which serum, liver and kidney samples were analysed for lipid profile, lipoprotein changes and fatty acid composition. While the alloxan‐induced diabetic rats showed a significant increase in the levels of cholesterol, triglycerides and free fatty acids, the levels in the animals treated with G. montanum leaves were considerably reduced and restored to near normal values. Antihyperlipidaemic effects of G. montanum leaves were found to be comparable with that of glibenclamide. Similarly, G. montanum leaves treatment resulted in reversal of alterations observed in the plasma lipoproteins (high‐density lipoprotein, low‐density lipoprotein and very high‐density lipoprotein‐cholesterol) and fatty acid composition in serum, liver and kidney of alloxan‐induced rats. Our study suggests that phytochemicals present in G. montanum may play an important role in suppressing the elevated lipid profile in diabetes and may be useful for the prevention and/or early treatment of diabetes‐associated hyperlipidaemia.     

Potential in vitro antioxidant and protective effects of Gymnema montanum H. on alloxan-induced oxidative damage in pancreatic β-cells, HIT-T15

The present study describes the antioxidant activities of ethanol extract from Gymnema montanum (GLEt) which is an endemic plant of India. Antioxidant activity of the GLEt was studied in vitro based on scavenging of hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, reducing power and inhibition of lipid peroxidation estimated in terms of thiobarbituric acid reactive substances (TBARS). Further, we examined its protective effect against alloxan-induced oxidative stress in pancreatic β-cells, HIT-T15 by measuring the free radical generation, malonaldehyde formation and antioxidant levels such as CAT, GPx and GSH. Results showed that G. montanum leaves exhibited significant antioxidant activities measured by various in vitro model systems. The HIT-T15 cell line studies showed the tendency of GLEt to increase antioxidant levels meanwhile decrease the free radical formation and inhibit the lipid peroxidation. The antioxidant activity was found to be well correlated with the phenolic phytochemicals present in the extract. GC–MS analyses revealed the presence of few phenolic compounds in the extract. As this plant has already been demonstrated for a variety of medicinal properties from our laboratory, results of this study suggest that G. montanum is an interesting source for antioxidant compounds and useful for various therapeutic applications.     

Inhibitory effect of Gymnema Montanum leaves on α-glucosidase activity and α-amylase activity and their relationship with polyphenolic content

The present study was attempted to investigate the effect of G. montanum leaf extract on inhibition of α-glucosidase and α-amylase activity. The ethanol extract of G. montanum (GLEt) at various concentrations (1–10 μg/ml) was tested for its inhibition pattern against α-glucosidase and α-amylase activity in vitro and compared with the commercially available α-glucosidase inhibitor, acarbose. The GLEt showed competitive inhibition against yeast α-glucosidase and noncompetitive inhibition against salivary α-amylase in a concentration-dependent manner. Further, we investigated the effect of extract on levels of blood glucose and plasma insulin in neonatal streptozotocin-induced type 2 diabetic rats. Long-term administration (12 weeks) of the GLEt effectively reduced the blood glucose level and also increased the insulin level. In a preliminary phytochemical analysis, G. montanum leaves were rich in phenolic composition and found to be positively correlated with the inhibitory effect of α-glucosidase and α-amylase activity. These results suggest that the GLEt might exert its antidiabetic effect by suppressing carbohydrate absorption from the intestine and thereby reducing hyperglycemia.     

Antidiabetic activity of Diospyros peregrina fruit: Effect on hyperglycemia, hyperlipidemia and augmented oxidative stress in experimental type 2 diabetes

Diospyros peregrina is an edible fruit of costal West-Bengal. The present investigation was undertaken to evaluate the role of aqueous extract of D. peregrina fruit in streptozotocin–nicotinamide induced type 2 diabetic rats. Oral administration of extract at the doses of 50 and 100 mg/kg body weight per day for 28 days to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity. An increased reactive oxygen species and insufficient antioxidant activity is associated with diabetes mellitus, which is mainly responsible for diabetic pathogenesis. The role of extract on antioxidant markers of liver and kidney were estimated. The diabetic rats exhibited lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract treated diabetic rats in selected tissues. The increased level of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxide) in diabetic rats was also found to be reverted back to near normal status in extract treated groups.     

Effect of grape (Vitis vinifera L.) leaf extract on alcohol induced oxidative stress in rats

Alcoholic liver disease is a major medical complication of drinking alcohol. Oxidative stress plays an important role in the development of alcohol liver disease. The present study was carried to evaluate the effect of grape leaf extract (GLEt) on antioxidant and lipid peroxidation states in liver and kidney alcohol induced toxicity. In vitro studies with DPPH* and ABTS*(+) (cation radical) showed that GLEt possesses antioxidant activity. In vivo administration of ethanol (7.9 g/kg bw/day) for 45 days resulted an activity of liver marker enzymes (AST, ALT, ALP and GGT), lipid peroxidation markers (TBARS, lipid hydroperoxides) in liver and kidney with significantly lower activity of SOD, CAT, GPx, GST and non-enzymatic antioxidants (vitamin E, vitamin C and GSH) in liver and kidney as compared with control rats. Administration of ethanol along with GLEt significantly decreased the activities of liver markers enzyme in serum towards near normal level. GLEt at a dose of 100 mg/kg was highly effective than 25 and 50 mg/kg body weight. In addition GLEt also significantly reduced the levels of lipid peroxidation and addition, significantly restored the enzymic and non-enzymatic antioxidants level in liver and kidney of alcohol administration rats. This observation was supplemented by histopathological examination in liver and kidney. Our data suggest that GLEt exerts its protective effect by decreased the lipid peroxidation and improving antioxidants status, thus proving itself as an effective antioxidant in alcohol induced oxidative damage in rats.     

Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin-induced diabetic rats

Oxidative stress plays an important role in chronic complications of diabetes. In the present study the antioxidant effect of oral administration of ethanolic extract of Eugenia jambolana seed kernel on tissue antioxidant enzymes and lipid peroxidation in liver and kidney of streptozotocin-induced diabetic rats was evaluated. Administration of seed kernel to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased body weight gain, plasma insulin and hemoglobin. The diabetic rats showed the low activities of superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione content in liver and kidney, which were restored to near normal levels by treatment with the seed kernel extract. The increased levels of lipid peroxidation and hydroperoxides in diabetic rats were reverted back to near normal levels after the treatment with seed kernel extract. Diabetic rats treated with seed kernel extract restored almost normal architecture of liver and kidney and were confirmed by histopathological examination. The present study reveals the efficacy of Eugenia jambolana seed kernel in the amelioration of diabetes, which may be attributed to its hypoglycemic property along with its antioxidant potential. The antioxidant effect of Eugenia jambolana seed kernel was also compared with glibenclamide, a standard hypoglycemic drug.     

Antidiabetic effect of Gymnema montanum leaves: effect on lipid peroxidation induced oxidative stress in experimental diabetes

Gymnema montanum is widely used in ancient medicine for the ailment of various diseases. Oral administration of 200 mg kg(-1) (body weight) BW of the alcoholic extract of the leaf for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin, whereas the effect of 50 and 100 mg kg(-1) BW was not significant. The alcoholic extract also resulted in decreased free radical formation in plasma of diabetic rats. Thus, this study shows that Gymnema montanum leaf extract (GLEt) possess antihyperglycemic and antiperoxidative effect. The decrease in lipid peroxides and increase in reduced glutathione (GSH), ascorbic acid (Vitamin C) and alpha-tocopherol (Vitamin E) clearly show the antioxidant properties of GLEt. The effect of GLEt was most prominently seen in the case of animals given 200 mg kg(-1) BW. In addition, the results suggest that GLEt was highly effective than the reference drug glibenclamide.     

Modulation of impaired cholinesterase activity in experimental diabetes: effect of Gymnema montanum leaf extract

We reported that a leaf extract (GLEt) obtained from an anti-diabetic plant, Gymnema montanum, an endangered species endemic to India, has anti-peroxidative and antioxidant effects on diabetic brain tissue in rats. Here we examined the effect of the extract on the activity of reduced brain and retinal acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in streptozotocin (STZ)-induced diabetic male Wistar rats. Diabetic rats received GLEt orally (200 mg/kg bwt/d) for 12 wk, and changes in blood glucose, plasma insulin, the lipid peroxidation marker thiobarbituric acid-reactive substance (TBARS), and AChE and BChE activity were measured. The results confirmed prior reports that hyperglycemia significantly enhances TBARS levels in brain and retinal tissue and decreases AChE and BChE activity. Treatment with GLEt significantly reversed the impairment in enzymatic activity in addition to reducing the level of TBARS, suggesting that GLEt protects against the adverse effect of lipid peroxidation on brain and retinal cholinesterases. We suggest that GLEt could be useful for preventing the cholinergic neural and retinal complications of hyperglycemia in diabetes.     

Influence of umbelliferone on membrane-bound ATPases in streptozotocin-induced diabetic rats

The activities of membrane-bound ATPases are altered both in erythrocytes and tissues of streptozotocin (STZ)-induced diabetic rats and diabetic patients. Umbelliferone (UMB), a natural antioxidant, is a benzopyrone occurring in nature, and it is present in the fruits of golden apple (Aegle marmelos Correa) and bitter orange (Citrus aurantium). Earlier we evaluated and reported the effect of UMB on plasma insulin and glucose, and this study was designed to evaluate the effect of umbelliferone on membrane-bound ATPases in erythrocytes and tissues (liver, kidney and heart) of STZ-induced diabetic rats. Adult male albino rats of Wistar strain, weighing 180-200 g, were made diabetic by an intraperitonial administration of STZ (40 mg/kg). Normal and diabetic rats were treated with UMB dissolved in 10% dimethyl sulfoxide (DMSO) and diabetic rats were also treated with glibenclamide as drug control, for 45 days. In our study, diabetic rats had increased level of blood glucose and lipid peroxidation markers, and decreased level of plasma insulin and decreased activities of total ATPases, (Na(+)+K(+))-ATPase, low affinity Ca(2+)-ATPase and Mg(2+)-ATPase in erythrocytes and tissues. Restoration of plasma insulin and glucose by UMB and glibenclamide seemed to have reversed insulin, glucose and lipid peroxidation markers, and diabetes-induced alterations in the activities of membrane-bound ATPases. Thus, our results show that the normalization of membrane-bound ATPases in various tissues, is due to improved glycemic control and antioxidant activity by UMB.     

Oxidative stress in rats after 60 days of hypergalactosemia or hyperglycemia

Two of the models used in current diabetes research include the hypergalactosemic rat and the hyperglucosemic, streptozotocin-induced diabetic rat. Few studies, however, have examined the concurrence of these two models regarding the effects of elevated hexoses on biomarkers of oxidative stress. This study compared the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase and the concentrations of glutathione, glutathione disulfide, and thiobarbituric acid reactants (as a measure of lipid peroxidation) in liver, kidney, and heart of Sprague-Dawley rats after 60 days of either a 50% galactose diet or insulin deficiency caused by streptozotocin injection. Most rats from both models developed bilateral cataracts. Blood glucose and glycosylated hemoglobin A(1c) concentrations were elevated in streptozotocin diabetic rats. Streptozotocin diabetic rats exhibited elevated activities of renal superoxide dismutase, cardiac catalase, and renal and cardiac glutathione peroxidase, as well as elevated hepatic lipid peroxidation. Insulin treatment of streptozotocin-induced diabetic rats normalized altered markers. In galactosemic rats, hepatic lipid peroxidation was increased whereas glutathione reductase activity was diminished. Glutathione levels in liver were decreased in diabetic rats but elevated in the galactosemic rats, whereas hepatic glutathione disulfide concentrations were decreased much more in diabetes than in galactosemia. Insulin treatment reversed/prevented all changes caused by streptozotocin-induced diabetes. Lack of concomitance in these data indicate that the 60-day galactose-fed rat is not experiencing the same oxidative stress as the streptozotocin diabetic rat, and that investigators must be cautious drawing conclusions regarding the concurrence of the effects of the two animal models on oxidative stress biomarkers.     

Antidiabetic and antioxidant activity of the methanol extract of Diospyros peregrina fruit on Type I diabetic rats

Chronic diabetes complications are mainly associated with augmented oxidative stress. Thus the present study evaluated the hypoglycemic, as well the antioxidant effect, of the methanol extract of Diospyros peregrina Gurke. (Ebenaceae) fruits on experimental diabetic rats. Oral administration of methanol extract at 150 and 300?mg/kg body weight per day to diabetic rats was found to have profound hypoglycemic activity in term of reduction of fasting blood glucose level. The diabetic rats showed lower activities of superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) content in hepatic and renal tissues as compared with normal rats. The activities of SOD, CAT, and GSH were found to be increased in extract-treated diabetic rats in selected tissues. The increased levels of lipid peroxidation (thiobarbituric acid reactive substances and hydroperoxides) in diabetic rats were also found to be reverted back to near-normal status in extract-treated groups. It was found that the extract is more effective at the dose of 300?mg/kg body weight and this effect is almost comparable to that of standard glibenclamide.     

Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats

Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.     

Protective Effects of d‐Limonene on Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin‐Induced Diabetic Rats

The aim of this study was to evaluate the protective effects of d ‐limonene on the levels of lipid peroxidation by‐products and antioxidant defence systems in the plasma and tissues of normal and streptozotocin (STZ)‐induced diabetes rats. The experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.) injection, and treatment with d ‐limonene was continued for 45 days. After the treatment period, oxidative stress parameters such as lipid peroxidation by‐products; enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione‐S‐transferase; non‐enzymic antioxidants including reduced glutathione, Vitamins C and E were measured in the plasma and tissues of experimental rats. An increase in the levels of lipid peroxidation by‐products and significant decrease in antioxidant enzymes were observed in untreated diabetic rats. Administration of d ‐limonene to diabetic rats for 45 days caused a significant reduction in the levels of lipid peroxidation by‐products and an increase in the activities of antioxidant enzymes, when compared with the untreated diabetic group. There was no significant difference in normal treated groups, when compared with normal rats. Biochemical observations were substantiated with the help of histopathological examinations through its antioxidant properties and thereby conferred protection against STZ‐induced diabetic rats. The result of this study indicates that d ‐limonene has antioxidant potential in addition to its antidiabetic effect in experimental diabetes.     

Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats

In the present study, the effect of alcoholic stem extract of Gymnema montanum (GMSt) on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg bw). Five days after STZ induction, diabetic rats received GMSt orally at the doses of 25, 50, 100 and 200 mg/kg daily for 3 weeks. Graded doses of stem extract showed a significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200 mg/kg than 50 mg/kg. GMSt showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats while there was significant reduction in the levels of glucose-6-phosphatase and fructose-1,6-bisphosphatase. The present study clearly indicated significant antidiabetic effect with the stem extract of G. montanum and lends support for its traditional usage.     

Protective effects of Phyllanthus amarus aqueous extract against renal oxidative stress in Streptozotocin -induced diabetic rats

Aim and Objectives:

In the present study, we have evaluated the antihyperglycemic, hypolipidemic and antioxidant activities of aqueous extract of Phyllanthus amarus (PAAEt) in streptozotocin (STZ)-induced diabetic rats.

Materials and Methods:

PAAEt was administered at 200 mg/kg body weight/day to normal treated (NT-group) and STZ-induced diabetic treated rats (DT-group) by gavage for eight weeks. During the experimental period, blood was collected from fasted rats at 10 days intervals and plasma glucose level was estimated. The plasma lipid profile was estimated at the end of experimental period. After the treatment, period kidney lipid peroxidation (LPO), protein oxidation and reduced glutathione (GSH) were estimated and antioxidant enzymes viz., glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), catalase (CAT) and superoxide dismutase (SOD) were also assayed.

Results:

The significant decrease in the body weight, hyperglycemia and hyperlipidemia observed in STZ-induced diabetic rats (D-group) were rectified with PAAEt treatment in diabetic treated group (DT-group). D-group rats showed increased renal oxidative stress with increased LPO and protein oxidation. DT-group showed a significant decrease in renal LPO, protein oxidation and a significant increase in GSH content and GR, GPx and GST activities when compared with D-group. The activities of SOD and CAT decreased significantly in D-group, but were normalized in DT-group. Normal rats treated with PAAEt (NT-rats) showed a significant decrease in lipid profile, renal LPO and protein oxidation, with significant increase in renal GSH and activities of antioxidant enzymes compared to normal rats (N-group).

Conclusion:

Our results demonstrated that PAAEt with its antidiabetic, hypolipidemic and antioxidant properties could be a potential herbal medicine in treating diabetes and renal problems.     

Effect of N-benzoyl-D-phenylalanine on streptozotocin-induced changes in the lipid and lipoprotein profile in rats

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin combination treatment on circulatory lipids, lipoproteins and lipid peroxidation markers were studied in neonatal streptozotocin (nSTZ) non-insulin dependent diabetic rats. Non-insulin dependent diabetes mellitus (NIDDM) was induced by a single dose injection of streptozotocin (100 mg kg(-1), i. p.) to two-day-old rats. After 10-12 weeks, rats weighing above 150 g were selected for screening for the NIDDM model. The rats were checked for fasting blood glucose levels to confirm the status of NIDDM. NBDP (50,100 or 200 mg kg(-1) ) was administered orally for six weeks to the confirmed diabetic rats (to evaluate the effective dose). The levels of serum lipids and lipid peroxidation markers were significantly increased, whilst the activity of glucose-6-phosphate dehydrogenase was significantly decreased in nSTZ diabetic rats. NBDP and metformin were able to restore the altered serum lipids, lipoproteins, lipid peroxidation marker levels and glucose-6-phosphate dehydrogenase activity to almost control levels. The results showed the antihyperlipidaemic properties of NBDP and metformin in addition to its antidiabetic action. Combination treatment was more effective then either drug alone. The results indicated that the coadministration of NBDP with metformin to nSTZ diabetic rats normalized blood glucose and caused marked improvement in altered serum lipids, lipoproteins and lipid peroxidation markers during diabetes. The data indicated that NBDP represented an effective antihyperglycaemic and antihyperlipidaemic adjunct for the treatment of diabetes, and may be a potential source of new orally active agents for future therapy.     

Garcinia kola seed ameliorates renal,hepatic, and testicular oxidative damage in streptozotocin-induced diabetic rats

Abstract

Context: In Africa, Garcinia kola Heckel (Guttiferae) seed is commonly recommended in folklore medicine for the treatment of diabetes and its associated complications.

Objective: The present study evaluated this traditional claim by mechanistic investigation into the effect of G. kola seed administration on renal, hepatic, and testicular oxidative damage in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Diabetes mellitus was induced in adult male Wistar rats by an intraperitoneal injection of STZ (50?mg/kg). The diabetic rats were thereafter treated orally once per day with G. kola seed (250?mg/kg) and monitored for 14?d. Clinical observations, plasma biochemistry, hormonal profile, oxidative stress indices, sperm characteristics, and histopathological examination of the kidney, liver, and testes were evaluated to monitor treatment-related effects of G. kola seed in STZ-induced diabetic rats.

Results and discussion: Garcinia kola seed administration significantly ameliorated hyperglycemia mediated damage by decreasing the blood glucose level (72.8% and 84.6% on the 7th and 14th post-treatment days, respectively), enhancement of the antioxidant system, inhibition of lipid peroxidation, and improving the architecture of the kidney, liver, and testes in STZ-induced diabetic rats. In addition, G. kola seed intervention restored the kidney and liver function biomarkers, the sperm characteristics as well as the plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, triiodothyronine (T₃), and thyroxine (T₄) to normal in STZ-induced diabetic rats.

Conclusion: The findings from this investigation provide persuasive scientific support for the traditional use of G. kola seed in the treatment of diabetes and its associated complications.     

Effect of the sulphonylurea glibenclamide on liver and kidney antioxidant enzymes in streptozocin-induced diabetic rats

BACKGROUND: Alterations in catalase (CAT) and superoxide dismutase (SOD) activity have been reported in diabetes mellitus. Glibenclamide (glyburide), a member of the second-generation sulphonylureas, provides effective treatment for patients with moderate diabetes. The action of the liver plays an important role in its glucose-lowering effect, suggesting that glibenclamide also exerts a direct effect on liver enzyme activities. OBJECTIVE: To evaluate the effect of glibenclamide on the activities of antioxidant enzymes (CAT and SOD) in liver and kidney tissue of diabetic rats. METHODS: Thirty-nine rats were included in this study. Moderate diabetes mellitus was induced with streptozocin (freshly dissolved in citrate buffer, ph 4.5) 55 mg/kg in 22 rats. Eight of these diabetic rats were left untreated, insulin was administered to six diabetic rats, and glibenclamide was administered to eight rats with moderate diabetes. Liver and kidney CAT and SOD activities were measured in all rats. RESULTS: Hepatic CAT and SOD activities were significantly reduced in diabetic animals (p < 0.05 for both activities). Glibenclamide treatment of diabetic rats for 5 weeks reversed the changes observed in diabetic liver tissues (p < 0.05). However, renal CAT and SOD activities were unchanged. In addition, high blood glucose levels of diabetic rats were decreased following glibenclamide treatment. CONCLUSION: Administration of glibenclamide to diabetic rats reversed diabetes-induced changes, suggesting that glibenclamide may directly increase liver CAT and SOD activity.     

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.     

Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocin–nicotinamide induced diabetic nephropathy

The present study aimed to evaluate the effect of alcohol (PA) and hydroalcohol (PHA) extract of Paeonia emodi Royale roots in treatment of streptozotocin–nicotinamide induced diabetic nephropathy. Diabetes mellitus was induced in male Wistar rats by streptozotocin (65 mg/kg intraperitoneally) 15 minutes after nicotinamide (230 mg/kg, intraperitoneally) administration and diabetic nephropathy was assessed by measuring serum glucose, renal parameters (urea, uric acid, creatinine, and blood urea nitrogen level) and lipid profile. The rats were treated with different doses of extracts (100 mg/kg, 200 mg/kg, and 400 mg/kg) for 45 days. Oxidative stress was assessed by measuring tissue antioxidant enzymes level along with the formation of advanced glycation end-products (AGEs) in kidney. PA and PHA (400 mg/kg) produced significant attenuation in the serum glucose level (165.08 ± 3.353 mg/dL and 154.27 ± 2.209 mg/dL, respectively) as compared to control. Elevated renal parameters, lipid levels, tissue antioxidant enzymes and AGE formation were also restored in a dose-dependent manner. These findings suggest that by amelioration of oxidative stress and formation of AGEs, PA and PHA significantly inhibited the progression diabetic nephropathy in rats.