Antidiabetic effects of scoparic acid D isolated from Scoparia dulcis in rats with streptozotocin-induced diabetes.

We evaluated the antihyperglycaemic effect of scoparic acid D (SAD), a diterpenoid isolated from the ethanol extract of Scoparia dulcis in streptozotocin (STZ)-induced diabetic male Wistar rats. SAD was administered orally at a dose of 10, 20 and 40 mg kg(-1) bodyweight for 15 days. At the end of the experimental period, the SAD-treated STZ diabetic rats showed decreased levels of glucose as compared with diabetic control rats. The improvement in blood glucose levels of SAD-treated rats was associated with a significant increase in plasma insulin levels. SAD at a dose of 20 mg kg(-1) bodyweight exhibited a significant effect when compared with other doses. Further, the effect of SAD was tested on STZ-treated rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. SAD at a dose of 20 microg mL(-1) evoked two-fold stimulation of insulin secretion from isolated islets, indicating its insulin secretagogue activity. Further, SAD protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. The present study thus confirms the antihyperglycaemic effect of SAD and also demonstrated the consistently strong cytoprotective properties of SAD.

Antihyperlipidemic effect of Scoparia dulcis (sweet broomweed) in streptozotocin diabetic rats.

We have investigated Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India, for its possible antihyperlipidemic effect in rats with streptozotocin-induced experimental diabetes. Oral administration of an aqueous extract of S. dulcis plant (200 mg/kg of body weight) to streptozotocin diabetic rats for 6 weeks resulted in a significant reduction in blood glucose, serum and tissue cholesterol, triglycerides, free fatty acids, phospholipids, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity, and very low-density lipoprotein and low-density lipoprotein cholesterol levels. The decreased serum high-density lipoprotein cholesterol, anti-atherogenic index, and HMG-CoA reductase activity in diabetic rats were also reversed towards normalization after the treatment. Similarly, the administration of S. dulcis plant extract (SPEt) to normal animals resulted in a hypolipidemic effect. The effect was compared with glibenclamide (600 microg/kg of body weight). The results showed that SPEt had antihyperlipidemic action in normal and experimental diabetic rats in addition to its antidiabetic effect.

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.

Scoparia dulcis, a traditional antidiabetic plant, protects against streptozotocin induced oxidative stress and apoptosis in vitro and in vivo.

Oxidative stress is implicated in the pathogenesis of diabetic complications. The experiments were performed on normal and experimental male Wistar rats treated with Scoparia dulcis plant extract (SPEt). The effect of SPEt was tested on streptozotocin (STZ) treated Rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. Administration of an aqueous extract of Scoparia dulcis by intragastric intubation (po) at a dose of 200 mg/kg body weight significantly decreased the blood glucose and lipid peroxidative marker thiobarbituric acid reactive substances (TBARS) with significant increase in the activities of plasma insulin, pancreatic superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in streptozotocin diabetic rats at the end of 15 days treatment. Streptozotocin at a dose of 10 mug/mL evoked 6-fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. The extract markedly reduced the STZ-induced lipidperoxidation in RINm5F cells. Further, SPEt protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. Treatment of RINm5F cells with 5 mM STZ and 10 mug of SPEt completely abrogated apoptosis induced by STZ, suggesting the involvement of oxidative stress. Flow cytometric assessment on the level of intracellular peroxides using fluorescent probe 2'7'-dichlorofluorescein diacetate (DCF-DA) confirmed that STZ (46%) induced an intracellular oxidative stress in RINm5F cells, which was suppressed by SPEt (21%). In addition, SPEt also reduced (33%) the STZ-induced apoptosis (72%) in RINm5F cells indicating the mode of protection of SPEt on RIN m5Fcells, islets, and pancreatic beta-cell mass (histopathological observations). Present study thus confirms antihyperglycemic effect of SPEt and also demonstrated the consistently strong antioxidant properties of Scoparia dulcis used in the traditional medicine.

Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats.

BACKGROUND: The aim of the study was to investigate the effect of aqueous extract of Scoparia dulcis on the occurrence of oxidative stress in the brain of rats during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system. METHODS: Aqueous extract of Scoparia dulcis plant was administered orally (200 mg/kg body weight) and the effect of extract on blood glucose, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were estimated in streptozotocin (STZ) induced diabetic rats. Glibenclamide was used as standard reference drug. RESULTS: A significant increase in the activities of plasma insulin, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was observed in brain on treatment with 200 mg/kg body weight of Scoparia dulcis plant extract (SPEt) and glibenclamide for 6 weeks. Both the treated groups showed significant decrease in TBARS and hydroperoxides formation in brain, suggesting its role in protection against lipidperoxidation induced membrane damage. CONCLUSIONS: Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the medicinal plant, these findings suggest a possible antiperoxidative role for Scoparia dulcis plant extract. Hence, in addition to antidiabetic effect, Scoparia dulcis possess antioxidant potential that may be used for therapeutic purposes.

Modulatory effect of Gymnema montanum leaf extract on brain antioxidant status and lipid peroxidation in diabetic rats.

The effects of leaf extract from Gymnema montanum, an endangered and endemic plant, were examined on brain lipid peroxidation in experimental diabetic rats. Ethanolic extract of G. montanum leaves was administered orally (50, 100, and 200 mg/kg of body weight) for 3 weeks, and changes in blood glucose, plasma insulin, and lipid peroxidation markers such as thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and levels of antioxidants, namely, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and glutathione-S-transferase, were examined in the brain of alloxan-induced diabetic rats. Glibenclamide was used as a standard reference drug. A significant increase in the activities of antioxidants was observed in brain on treatment with G. montanum leaf extract and glibenclamide for 3 weeks. Both the treated groups showed significant decreases in formation of TBARS and hydroperoxides in brain, suggesting a role in protective action against lipid peroxidation-mediated membrane damage. Our findings indicate that G. montanum leaf extract possesses antiperoxidative and antioxidant effects in addition to its antidiabetic activity. This report helps to create awareness on the need for conservation of medicinal plants, and G. montanum is one such plant that needs to be conserved through various propagation trials.

Insulin-secretagogue activity and cytoprotective role of the traditional antidiabetic plant Scoparia dulcis (Sweet Broomweed).

Scoparia dulcis (Sweet Broomweed) has been documented as a traditional treatment of diabetes. The administration of an aqueous extract of Scoparia dulcis at a dose of 200 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in streptozotocin diabetic rats at the end of 15 days treatment. The insulin secretagogue action of Scoparia dulcis plant extract (SPEt) was further investigated using isolated pancreatic islets from mice. SPEt at a dose of 10 microg/ml evoked 6.0 fold stimulation of insulin secretion from isolated islets indicating its insulin secretagogue activity. In addition the effect of SPEt on streptozotocin induced cell death and nitric oxide (NO) in terms of nitrite production were also examined. SPEt protected against streptozotocin- mediated cytotoxicity (88%) and NO production in rat insulinoma cell line (RINm5F). Above results suggest the glucose lowering effect of SPEt to be associated with potentiation of insulin release from pancreatic islets. Our results revealed the possible therapeutic value of Scoparia dulcis for the better control, management and prevention of diabetes mellitus progression.

Effect of Scoparia dulcis extract on insulin receptors in streptozotocin induced diabetic rats: studies on insulin binding to erythrocytes.

We investigated the insulin-receptor-binding effect of Scoparia dulcis plant extract in streptozotocin (STZ)-induced male Wistar rats, using circulating erythrocytes (ER) as a model system. An aqueous extract of S dulcis plant (SPEt) (200 mg/kg body weight) was administered orally. We measured blood levels of glucose and plasma insulin and the binding of insulin to cell-membrane ER receptors. Glibenclamide was used as standard reference drug. The mean specific binding of insulin to ER was significantly lower in diabetic control rats (DC) (55.0 +/- 2.8%) than in SPEt-treated (70.0 +/- 3.5%)- and glibenclamide-treated (65.0 +/- 3.3%) diabetic rats, resulting in a significant decrease in plasma insulin. Scatchard plot analysis demonstrated that the decrease in insulin binding was accounted for by a lower number of insulin receptor sites per cell in DC rats when compared with SPEt- and glibenclamide-treated rats. High-affinity (Kd1), low-affinity (Kd2), and kinetic analysis revealed an increase in the average receptor affinity in ER from SPEt and glibenclamide treated diabetic rats having 2.5 +/- 0.15 x 10(10) M(-1) (Kd1); 17.0 +/- 1.0 x 10(-8) M(-1) (Kd2), and 2.0 +/- 0.1 x 10(-10) M(-1) (Kd1); 12.3 +/- 0.9 x 10(-8) M(-1) (Kd2) compared with 1.0 +/- 0.08 x 10(-10) M(-1) (Kd1); 2.7 +/- 0.25 x 10(-8) M(-1) (Kd2) in DC rats. The results suggest an acute alteration in the number of insulin receptors on ER membranes in STZ-induced diabetic rats. Treatment with SPEt and glibenclamide significantly improved specific insulin binding, with receptor number and affinity binding (p < 0.001) reaching almost normal non-diabetic levels. The data presented here show that SPEt and glibenclamide increase total ER membrane insulin binding sites with a concomitant significant increase in plasma insulin.

Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate metabolic enzymes in alloxan-induced diabetic rats.

The effects of Gymnema montanum, an endangered plant used in the ancient period of India, on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in alloxan diabetic rats. Administration of alcoholic extract of G. montanum leaves (50, 100, 200 mg/kg body weight) to alloxan diabetic rats for 3 weeks reduced the blood glucose level. Administration of G. montanum leaf extract (GLEt) at 200 mg/kg body weight significantly decreased the blood glucose levels and significantly increased the plasma insulin levels. This clearly shows the antidiabetic efficacy of GLEt, which was better than that of glibenclamide.

Preventive effects of Cassia auriculata L. flowers on brain lipid peroxidation in rats treated with streptozotocin.

The effect of aqueous extract of the flowers of Cassia auriculata were examined on antioxidants and lipid peroxidation in the brain of streptozotocin diabetic rats. Significant increase in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in brain on treatment with Cassia auriculata flower extract (CFEt) and glibenclamide. Both the treated groups showed significant decrease in thiobarbituric reactive substances (TBARS) and hydroperoxide formation in brain, suggesting its role in protection against lipid peroxidation induced membrane damage. Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of medicinal plant, these findings are suggestions of possible antiperoxidative role played by Cassia auriculata flower extract.

Antihyperglycaemic effect of Cassia auriculata in experimental diabetes and its effects on key metabolic enzymes involved in carbohydrate metabolism.

1. In experimental diabetes, enzymes of glucose and fatty acid metabolism are markedly altered. Persistent hyperglycaemia is a major contributor to such metabolic alterations, which lead to the pathogenesis of diabetic complications. To our knowledge, there are no available reports on the enzymes of hepatic glucose metabolism of Cassia auriculata flower against diabetes. The present study was designed to study the effect of Cassia auriculata flower extract (CFEt) on hepatic glycolytic and gluconeogenic enzymes. 2. Streptozotocin diabetic rats were given CFEt (0.15, 0.30 and 0.45 g/kg) or 600 microg/kg glibenclamide for 30 days. At the end of 30 days, blood glucose, plasma insulin, haemoglobin, glycosylated haemoglobin, glycolytic and gluconeogenic enzymes were assessed. 3. Administration of CFEt at 0.45 g/kg significantly decreased blood glucose, glycosylated haemoglobin and gluconeogenic enzymes and increased plasma insulin, haemoglobin and hexokinase activity. Similarly, administration of glibenclamide showed a significant effect; however, CFEt at 0.15 and 0.30 g/kg did not show any significant effect. 4. In conclusion, the observations show that the aqueous extract of CFEt possesses an antihyperglycaemic effect and suggest that enhanced gluconeogenesis during diabetes is shifted towards normal and that the extract enhances the utilization of glucose through increased glycolysis. The effect of CFEt was more prominent than that of glibenclamide.