Antinociceptive effect of Teucrium polium leaf extract in the diabetic rat formalin test

This study was designed to evaluate the analgesic effect of Teucrium polium leaf extract in the diabetic rat formalin test. For this purpose, streptozotocin (STZ)-diabetic rats received intraperitoneal injection of this extract (100 and 200 mg/kg per day) for a period of 2 weeks. It was found out that Teucrium polium-treated diabetic rats exhibited a lower nociceptive score as compared to untreated diabetics. The results may suggest therapeutic potential of Teucrium polium extract for the treatment of diabetic hyperalgesia.     

Hypoglycemic effects of Teucrium polium

Teucrium polium has a folk reputation as a hypoglycemic agent. The hypoglycemic activity of an aqueous decoction of plant aerial parts was tested in normoglycemic and streptozotocin-hyperglycemic rats. Results indicate that this extract caused significant reductions in blood glucose concentration 4 h after intravenous administration and 24 h after intraperitoneal administration. This effect could be due to enhancement of peripheral metabolism of glucose rather than an increase in insulin release.     

Hypoglycaemic effect of Triticum repens P. Beauv. in normal and diabetic rats

The hypoglycaemic effect of an aqueous extract of Triticum repens (TR) rhizomes was investigated in normal and streptozotocin (STZ) diabetic rats. After a single oral administration of the aqueous extract (20mg/kg) a significant decrease on blood glucose levels in STZ diabetic rats (p<0.001) was observed; the blood glucose levels were normalized after 2 weeks of daily oral administration of TR aqueous extract (20mg/kg) (p<0.001). Significant reduction on blood glucose levels were noticed in normal rats after both acute (p<0.001) and chronic treatment (p<0.001). In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of TR exhibits a potent hypoglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats

The hypoglycaemic effect of an aqueous extract of Lepidium sativum L. (LS) seeds was investigated in normal and streptozotocin (STZ)-induced diabetic rats. After a acute (single dose) or chronic (15 daily repeated administration) oral treatments, the aqueous LS extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (p < 0.001); the blood glucose levels were normalised 2 weeks after daily repeated oral administration of aqueous LS extract (20 mg/kg) (p < 0.001). Significant reduction on blood glucose levels were noticed in normal rats after both acute (p < 0.01) and chronic treatment (p < 0.001). In addition, no changes were observed in basal plasma insulin concentrations after treatment either in normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of LS exhibits a potent hypoglycaemic activity in rats without affecting basal plasma insulin concentrations.     

Hypoglycaemic effect of Clausena anisata (Willd) Hook methanolic root extract in rats

This study was designed to examine the hypoglycaemic effect of Clausena anisata (Willd) Hook [family: Rutaceae] root methanolic extract in normal (normoglycaemic) and in streptozotocin-treated diabetic rats. Young adult, male Wistar rats (Rattus norvegicus) weighing 250-300 g were used. Diabetes mellitus was induced in the group of diabetic 'test' rats by intraperitoneal injections of streptozotocin (STZ, 90 mg/kg). In one set of experiments, graded doses of the methanolic root extract of C. anisata (CAME, 100-800 mg/kg p.o.) were administered to both fasted normal and fasted diabetic rats. In another set of experiments, 800 mg/kg of CAME, a dose of the plant extract which produced maximal hypoglycaemic effect in both fasted normal and diabetic rats in the previous set of experiments, was used. The hypoglycaemic effect of this single dose of C. anisata root methanolic extract (i.e. CAME, 800 mg/kg p.o.) was compared with those of insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) in both fasted normal and fasted diabetic rats. Following acute treatment, relatively moderate to high doses of CAME (100-800 mg/kg p.o.) produced dose-dependent, significant reductions (P<0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. On their own, both insulin (5 micro U/kg s.c.) and glibenclamide (0.2 mg/kg p.o.) produced significant reductions (P<0.01-0.001) in the blood glucose concentrations of the fasted normal and diabetic rats. At a dose of 800 mg/kg p.o., CAME reduced the mean basal blood glucose concentrations of fasted normal and fasted diabetic rats by 57.52 and 51.30%, respectively. C. anisata contains a diverse group of chemical compounds (see Table 1). Since methanol extractives of plants are usually known to contain many chemical compounds, each of which is capable of producing definite biological activities via different mechanisms, it is difficult to draw any logical conclusion on the mechanism of the hypoglycaemic effect of such a diverse mixture of chemical compounds contained in the plant extract used in this study. While it is possible that the hypoglycaemic effect of the plant extract may be due, at least in part, to its terpenoid and coumarin contents, the mechanism of its hypoglycaemic action remains largely speculative, and is unlikely to be due to the stimulation of pancreatic beta-cells and subsequent secretion of insulin. Although C. anisata root methanolic extract is less potent than insulin as an antidiabetic agent, the results of this experimental animal study indicate that the herb possesses hypoglycaemic activity; and thus lend credence to the suggested folkloric use of C. anisata root in the management and/or control of adult-onset, Type-2 diabetes mellitus in some communities of South Africa.     

Phlorizin-like effect of Fraxinus excelsior in normal and diabetic rats

The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of the aqueous extract perfusion of Fraxinus excelsior L. (FE) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within four hours after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous extract at a dose of 10 mg/kg/h produced a significant decrease in blood glucose levels in normal rats (P < 0.001) and even more in diabetic rats (P < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of FE, since the basal plasma insulin concentrations were unchanged after FE treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (P < 0.001). We conclude that aqueous extract perfusion of FE caused a potent inhibition of renal glucose reabsorption. This renal effect might be at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

Study of hypoglycaemic and hypolipidemic effects of Inula viscosa L. aqueous extract in normal and diabetic rats

The present study was designed to examine the hypoglycaemic and hypolipidemic activity of Inula viscsa aqueous extract on normal and diabetic rats. In normal rats, a significant reduction in blood glucose levels 2 h was observed after a single oral administration (p<0.001). Repeated daily oral administration significantly reduced blood glucose levels after 4 days of treatment (p<0.01). In diabetic rats, a significant reduction in blood glucose levels was observed 1 h after a single oral administration (p<0.001). Repeated oral administration reduced blood glucose levels at the 4th day (p<0.001). No change in total plasma cholesterol and triglyceride levels was observed after both a single and repeated oral administration in both normal and diabetic rats. In addition, plasma insulin levels and body weight remained unchanged after 15 days of repeated oral administration in normal and diabetic rats. We conclude that Inula viscosa possess a hypoglycaemic but not hypolipidemic activity in normal and diabetic rats. The observed hypoglycaemic activity seems to be independent of insulin secretion.     

Hypoglycaemic activity of Retama raetam in rats

The purpose of this study was to determine the underlying mechanism of the hypoglycaemic activity of an aqueous extract perfusion of Retama raetam (RR) in normal and streptozotocin-induced diabetic rats. The aqueous extract was administered intravenously and the blood glucose changes were determined within 4 h after starting the treatment. Plasma insulin concentrations and glycosuria were determined. The aqueous RR extract at a dose of 10 mg[sol ]kg[sol ]h produced a significant decrease in blood glucose levels in normal rats (p < 0.001) and an even more marked decrease in diabetic rats (p < 0.001). This hypoglycaemic effect might be due to an extra-pancreatic action of the aqueous extract of RR, since the basal plasma insulin concentrations were unchanged after RR treatment. A potent increase of glycosuria was observed both in normal and diabetic rats (p < 0.001). It is concluded that an aqueous extract perfusion of RR caused a potent inhibition of renal glucose reabsorption. This renal effect is at least one mechanism to explain the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

Antihyperglycemic effect of the fruit-pulp of Eugenia jambolana in experimental diabetes mellitus

The oral antihyperglycemic effect of the water and ethanolic extracts of the fruit-pulp of Eugenia jambolana (EJ) was investigated in alloxan-induced diabetic with fasting blood glucose between 120 and 250 mg/dl as well as severely diabetic rabbits (fasting blood glucose above 250 mg/dl). Water extract was found to be more effective than the ethanolic extract in reducing fasting blood glucose and improving blood glucose in glucose tolerance test. Chromatographic purification of the water extract yielded not only two hypoglycaemic fractions (F-III more active than F-IV) but indicated the presence of hyperglycemic compounds (F-I and F-II) also in the water extract of Eugenia jambolana fruits. When administered as a single dose of 25 mg/kg of body weight; F-III could reduce fasting blood glucose from 174.0 +/- 4.6 to 137.3 +/- 5.4 mg/dl in diabetic (21% fall) and from 266.0 +/- 5.4 to 202.2 +/- 5.2 mg/dl in severely diabetic rabbits (24% fall). After treatment of diabetic and severely diabetic rabbits daily once with 25mg/kg, body weight with F-III for 7 and 15 days, respectively, there was fall in fasting blood glucose (38% diabetic; 48% severely diabetic) and improvement in blood glucose during glucose tolerance test (48%) in diabetic rabbits. Further, there was increase in the plasma insulin levels in both diabetic (24.4%) and severely diabetic rabbits (26.3%). The in vitro studies with pancreatic islets showed that the insulin release was nearly two and half times more than that in untreated diabetic rabbits. The mechanism of action of FIII fraction appears to be both pancreatic by stimulating release of insulin and extra pancreatic by directly acting on the tissues.     

Effect of Lepidium sativum L. on renal glucose reabsorption and urinary TGF-beta 1 levels in diabetic rats

The purpose of this study was to determine the mechanism underlying the hypoglycaemic activity of the aqueous extract perfusion of Lepidium sativum L. (LS) in normal and streptozotocin-induced diabetic rats. The aqueous LS extract was administered intravenously and the blood glucose levels were determined within 4 h of treatment. Plasma insulin concentrations and glycosuria were determined. The 24 h urinary transforming growth factor-beta1 (ELISA) was evaluated in diabetic and control rats 15 days after oral treatment with the aqueous LS extract at a dose of 20 mg/kg. The study showed that LS at a dose of 10 mg/kg/h reduced blood glucose levels both in normal and diabetic rats (p < 0.001). At the same time as a potent increase of glycosuria was observed both in normal and diabetic rats (p < 0.001). In addition, oral administration of LS for 15 days normalized glycaemia (p < 0.001), enhanced glycosuria (p < 0.05 vs diabetic control) and decreased the amount of urinary TGF-beta1 (p < 0.01) in diabetic rats. It is concluded that the aqueous LS extract caused a potent inhibition of renal glucose reabsorption which in turn reduced blood sugar. This renal effect is at least one mechanism explaining the observed hypoglycaemic activity of this plant in normal and diabetic rats.     

The antidiabetic activity of the herbal preparation ADD-199 in mice: a comparative study with two oral hypoglycaemic drugs

The antidiabetic and antioxidant effects of the herbal preparation ADD-199 were investigated in STZ-induced diabetic C(3)H mice and results were compared with two allopathic hypoglycaemic drugs, glibenclamide and metformin. Plasma glucose, insulin and lipids as well as liver glycogen, lipids and lipid peroxidation were measured following treatment for 8 weeks. The results indicated that plasma insulin levels in normal controls at termination were about 76 micromol/L compared to trace levels in untreated diabetic mice. Glibenclamide and ADD-199 increased insulin levels in diabetic mice up to 70% of levels in untreated non-diabetic mice whilst metformin had no effect. Basal plasma glucose levels in diabetic controls (18.8 mM) were reduced to 14.0 mM by 100 mg/kg ADD-199 in <2 weeks compared to 4 and 6 weeks for glibenclamide and metformin, respectively. This hypoglycaemic effect of ADD-199 appeared to be associated with the alkaloidal content of the extract. Treatment with ADD-199 or the hypoglycaemic agents reversed the observed elevation in plasma lipids but increased hepatic glycogen, triacylglycerol and cholesterol levels. Treatment also increased glucose uptake by isolated diaphragms and attenuated hepatic lipid peroxidation. These antihyperglycaemic and antioxidant actions of ADD-199 at a dose of 100mg/kg/day are comparable to those of the maximum daily therapeutic doses of glibenclamide (0.25 mg/kg) and metformin (50 mg/kg). These could explain the basis for use of this plant extract to manage diabetes mellitus (DM).     

Glucose lowering effect of aqueous extract of Enicostemma littorale Blume in diabetes: a possible mechanism of action

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. Enicostemma littorale Blume is a small herb and recently we have reported its blood glucose lowering potential in alloxan induced diabetic rats. A single dose of aqueous extract of E. littorale (15 g dry plant equivalent extract per kg) had shown significant increase in the serum insulin levels in alloxan-induced diabetic rats at 8 h. The insulinotropic action of aqueous extract of E. littorale was further investigated using rat pancreatic islets. Extract has the potential to enhance glucose-induced insulin release at 11.1 mM glucose from isolated rat pancreatic islets and was partially able to reverse the effect of diazoxide (0.25 mM). Incubation with Ca(2+) chelator (EGTA) and Ca(2+) channel blocker (nimodipine) did not affect the glucose-induced insulin release augmented by the extract. Above results suggest the glucose lowering effect of aqueous extract of E. littorale to be associated with potentiation of glucose-induced insulin release through K(+)-ATP channel dependent pathway but did not require Ca(2+) influx.     

Effect of the desert plant Retama raetam on glycaemia in normal and streptozotocin-induced diabetic rats

The effect of the aqueous extract of Retama raetam (RR) on blood glucose levels was investigated in fasting normal and streptozotocin-induced diabetic rats after single and repeated oral administration. The aqueous extract of RR at a dose of 20mg/kg significantly reduced the blood glucose in normal rats 6h after a single oral administration (P<0.005) and two weeks after repeated oral administration (P<0.05). This hypoglycaemic effect is more pronounced in streptozotocin (STZ) diabetic rats (P<0.001). The aqueous extract of RR had no effect on basal plasma insulin levels indicating that the underlying mechanism of RR activity is extra-pancreatic. These findings suggest that the aqueous extract of RR possess significant hypoglycaemic effect in both normal and STZ diabetic rats.     

Study of the hypoglycaemic activity of Fraxinus excelsior and Silybum marianum in an animal model of type 1 diabetes mellitus

The hypoglycaemic effect of the aqueous extracts of Fraxinus excelsior (FE) seed and Silybum marianum (SM) aerial part was investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 15 daily doses, oral administration of the aqueous extracts (20 mg/kg) produced a significant decrease of blood glucose levels in both normal and STZ diabetic rats (P < 0.001). From the first week, the body weight was increased in normal rats (P < 0.05) and decreased in STZ rats (P < 0.01) after FE administration. In addition, no changes were observed in basal plasma insulin concentrations after both FE and SM treatments in either normal and STZ diabetic rats indicating that these plants exert their pharmacological activity without affecting insulin secretion. We conclude that the aqueous extracts of FE and SM exhibit potent hypoglycaemic and anti-hyperglycaemic activities in normal and STZ rats, respectively, without affecting basal plasma insulin concentrations.     

Effect of Salvia officinalis L. leaves on serum glucose and insulin in healthy and streptozotocin-induced diabetic rats

The leaves of sage (Salvia officinalis L., Lamiaceae) are reported to have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, astringent, eupeptic and anti-hydrotic effects. To determine the hypoglycaemic effect of sage leaves, we investigated the effects of essential oil and methanolic effect of the plant on healthy and streptozotocin-induced diabetic rats. The animals were made diabetic using by streptozotocin (70 mg/kg, i.p.). The methanolic extract (100, 250, 400 and 500 mg/kg) and essential oil (0.042, 0.125, 0.2 and 0.4 ml/kg) were injected intraperitoneally. The control groups were administered water and sunflower oil as vehicles of methanolic extract and essential oil, respectively. Blood samples were obtained from retro-orbital sinus before administration and 1, 3 and 5 h after administrations. The serum glucose was measured by the enzymatic method of glucose oxidase. The results showed that the essential oil of sage did not change serum glucose, while the plant extract significantly decreased serum glucose in diabetic rats in 3 h without effect on insulin releasing from the pancreas but not in healthy rats. Also, the LD₅₀ of the methanolic extract is measured (4000 mg/kg, i.p.). The present data indicate that sage extract has hypoglycaemic effect on diabetic animals and the plant should be considered in future therapeutic researches.     

Caraway and caper: potential anti-hyperglycaemic plants in diabetic rats

The hypoglycaemic effect of aqueous extracts of Carum carvi (CC) and Capparis spinosa L. (CS) fruit were investigated in normal and streptozotocin (STZ) diabetic rats. After a single dose or 14 daily doses, oral administration of the aqueous CC and CS extracts (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P < 0.001); the blood glucose levels were nearly normalised 2 weeks after daily repeated oral administration of both aqueous CC and CS extracts (20 mg/kg) (P < 0.001). No highly significant changes on blood glucose levels were noticed in normal rats after both acute and chronic treatments with CS and CC. In addition, no changes were observed in basal plasma insulin concentrations after treatment with these plants in either normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that aqueous extracts of CC and CS exhibit a potent anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Anti-hyperglycaemic activity of the aqueous extract of Origanum vulgare growing wild in Tafilalet region

The effect of an aqueous extract of Origanum vulgare (OV) leaves on blood glucose levels was investigated in normal and streptozotocin (STZ) diabetic rats. In normal rats, the blood glucose levels were slightly decreased 6 h after a single oral administration (P<0.05) as well as 15 days after once daily repeated oral administration of aqueous OV extract (P<0.05) (20 mg/kg). After a single dose or 15 daily doses, oral administration of the aqueous extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats (P<0.001). In STZ rats, the blood glucose levels were normalised from the fourth day after daily repeated oral administration of aqueous OV extract (20 mg/kg) (P<0.001). However, this effect was less pronounced 2 weeks after daily repeated oral administration of OV extract. In addition, no changes were observed in basal plasma insulin concentrations after treatment in either normal or STZ diabetic rats indicating that the aqueous OV extract acted without changing insulin secretion. We conclude that an aqueous extract of OV exhibits an anti-hyperglycaemic activity in STZ rats without affecting basal plasma insulin concentrations.     

Hypoglycaemic activity of Anthocleista vogelii (Planch) aqueous extract in rodents

The hypoglycaemic effect of Anthocleista vogelii was studied in mice, rats and rabbits. Aqueous extract of the plant obtained by infusion from finely pulverized root was used. The extract (100, 400 and 800 mg/kg) induced significant hypoglycaemic activity in a dose-related fashion at 2 h after oral administration in mice and rats with ED₂₅ of 250 mg/kg and 350 mg/kg respectively. The extract (800 mg/kg, orally) similarly induced statistically significant lowering of blood glucose levels at 8 h in normoglycaemic rabbits. The extract (400 mg/kg and 800 mg/kg, orally) also caused reduction of blood glucose levels in alloxan-induced diabetic animals. The results of this study indicate that the aqueous extract of the roots of Anthocleista vogelii possess favourable hypoglycaemic activity both in normo and hyperglycaemic animals compared to chlorpropamide as a standard.     

Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats

The present study was designed to investigate the hypoglycemic and hypolipidemic properties of an ethanolic extract of Cichorium intybus (CIE) which is widely used in India as a traditional treatment for diabetes mellitus. Male Sprague-Dawley rats aged 9 weeks (160-200 g) were administered with streptozotocin (STZ, 50mg/kg) intraperitoneally to induce experimental diabetes. The Cichorium intybus whole plant was exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and freeze dried to get powder. Hypoglycemic effects of CIE were observed in an oral glucose tolerance test (OGTT) in which, a dose of 125 mg of plant extract/kg body weight exhibited the most potent hypoglycemic effect. Moreover, daily administration of CIE (125 mg/kg) for 14 days to diabetic rats attenuated serum glucose by 20%, triglycerides by 91% and total cholesterol by 16%. However, there was no change in serum insulin levels, which ruled out the possibility that CIE induces insulin secretion from pancreatic beta-cells. In addition, hepatic glucose-6-phosphatase activity (Glc-6-Pase) was markedly reduced by CIE when compared to the control group. The reduction in the hepatic Glc-6-Pase activity could decrease hepatic glucose production, which in turn results in lower concentration of blood glucose in CIE-treated diabetic rats. In conclusion, our results support the traditional belief that Cichorium intybus could ameliorate diabetic state.     

Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture

Aim of the study

The leaves of Costus pictus D. Don were used extensively for its antihyperglycemic activity by the people in Kerala, India. In the present study, the antihyperglycemic and insulin secretory activity of an aqueous extract of Costus pictus leaf extract was investigated in streptozotocin induced diabetic rats.

Materials and methods

Oral Glucose Tolerance Test was done to determine the effective dose of Costus pictus extract. Aqueous extract of Costus pictus leaves was given orally to the diabetic rats for 14 days. The insulin secretory action of the leaf extract was investigated using isolated pancreatic islets from rat. Liver glucose uptake activity was measured using d-[¹⁴C] glucose.

Results

The oral administration of an aqueous extract of Costus pictus at a dose of 250 mg/kg body weight significantly decreased the blood glucose with significant increase in plasma insulin level in diabetic rats at the end of 14 days treatment. The Costus pictus leaf extract significantly increased glucose induced insulin secretion at both 4 mM and 20 mM glucose concentrations which represents normal physiological and diabetic condition respectively. The decreased glucose uptake activity of the liver of diabetic rats was reverted to near normal levels after the treatment with Costus pictus leaf extract.

Conclusion

Our results suggest the glucose lowering effect of Costus pictus to be associated with the potentiation of insulin release from pancreatic islets and enhancement of peripheral utilization of glucose.