In vivo assessment of antidiabetic and antioxidant activities of rosemary (Rosmarinus officinalis) in alloxan-diabetic rabbits

Rosemary (Rosmarinus officinalis), used in traditional Turkish folk medicine for the treatment of hyperglycaemia, is widely accepted as one of the medicinal herb with the highest antioxidant activity. Accordingly, the present study was designed to investigate the possible actions of ethanolic extract of the leaves of Rosmarinus officinalis on glucose homeostasis and antioxidant defense in rabbits. In the first set of experiments, hypoglycaemic effects of oral administration of various doses (50, 100 and 200 mg/kg) of the extract were examined in normoglycaemic and glucose-hyperglycaemic rabbits. Optimal effect was observed in both of the animal groups with a dose of 200 mg/kg of the extract and this activity was independent from the effects of insulin. In another part of experiments, acute effect of various doses of the Rosmarinus officinalis extract on blood glucose and serum insulin levels was studied in alloxan-induced diabetic rabbits. Of the three doses of extract, the highest dose (200 mg/kg) significantly lowered blood glucose level and increased serum insulin concentration in alloxan-diabetic rabbits. The last set of experiments designed to investigate the subacute effect of the Rosmarinus officinalis extract on repeated administration in alloxan-diabetic rabbits. At the doses of 100 and 200 mg/kg, antihyperglycaemic effect of extract was accompanied by a significant increase in serum insulin levels in diabetic rabbits. Furthermore, during 1 week of treatment of diabetic rabbits with a dose of 200 mg/kg of the extract showed that the extract possessed a capability to inhibit the lipid peroxidation and activate the antioxidant enzymes. It was concluded that probably, due to its potent antioxidant properties, the Rosmarinus officinalis extract exerts remarkable antidiabetogenic effect.     

Effect of Zizyphus sativa leaves on blood glucose levels in normal and alloxan-diabetic rats

An alcoholic extract of Zizyphus sativa leaves was tested for hypoglycemic activity in normal and alloxan-diabetic rats. Single (100-400 mg/kg) oral doses of extract to normal animals showed a dose-dependent statistically significant lowering of blood glucose 2, 4 and 6 h later. The effect was most pronounced at 6 h with blood glucose returning to control values at 24 h. In alloxan-diabetic rats, no significant effect was observed with extract and tolbutamide. The minimum lethal dose was greater than 3000 mg/kg, orally in mice.     

Hypoglycaemic effects of myrtle oil in normal and alloxan-diabetic rabbits

Myrtus communis L. (Myrtaceae) leaves as well as the volatile oil (Myrtii Oleum; MO) obtained from the leaves are used to lower the blood glucose level in type-2 diabetic patients in Turkish folk medicine. However, little attention has been paid to the therapeutic use of this plant. The present study was designed to investigate the oral hypoglycaemic activity of single and multiple doses of MO in normal and alloxan-diabetic rabbits. MO did not show any effect in normoglycaemic rabbits either in single or multiple dose administrations, but a good hypoglycaemic activity was observed 4 h after the administration to diabetic animals at 50 mg/kg. To investigate the effect of MO on repeated administration in both normal and diabetic rabbits, it was administered in 50 and 100 mg/kg doses once a day for one week. MO significantly lowered blood glucose by 51% in alloxan-diabetic rabbits on the fourth hour and the following days at a dose of 50 mg/kg (P < 0.001). The hypoglycaemic dose (50 mg/kg) was also determined by performing the oral glucose tolerance test (OGTT) in normal rabbits. The hypoglycaemic effect of the MO was 21% higher in rabbits, which received the glucose load orally, when compared with control group. However, MO did not affect serum insulin concentrations in normal and alloxan-diabetic rabbits but reduced the serum triglyceride concentrations by 14% in alloxan-diabetic rabbits. The above observations show that MO exerts hypoglycaemic as well as mild hypotriglyceridemic activity in diabetic animals. The reduction in blood glucose level may be due to the reversible inhibition of alpha-glucosidases present in the brush-border of the small intestinal mucosa, higher rate of glycolysis as envisaged by the higher activity of glucokinase, as one of the key enzymes of glycolysis, and enhanced rate of glycogenesis as evidenced by the higher amount of liver glycogen present after MO administration.     

Hypoglycemic effects of Murraya koenigii on normal and alloxan-diabetic rabbits

In past there have been many medicinal plants, which have been used in traditional medicines for their antidiabetic properties without any scientific support and pharmacological evidence. The aqueous extract of Murraya koenigii leaves has been taken to evaluate the hypoglycemic activity in normal and alloxan induced diabetic rabbits. This plant is promising as it is widely and regularly used as a spice for food flavoring and as such it appears to be without any side effects and toxicity. Adequate characterization of hypoglycemic activity of aqueous extract has not been yet done, as no such reports are available in the literature though the activity is reported. The scientific evaluation of its hypoglycemic activity was, therefore, explored and also compared with the effect of a standard hypoglycemic drug, tolbutamide. A single oral administration of variable dose levels (200, 300 and 400 mg/kg) of aqueous extract led to lowering of blood glucose level in normal as well as in diabetic rabbits. The maximum fall of 14.68% in normal and 27.96% in mild diabetic was observed after 4 h of oral administration of 300 mg/kg. The same dose also showed a marked improvement in glucose tolerance of 46.25% in sub-diabetic (AR) and 38.5% in mild diabetic rabbits in glucose tolerance test after 2 h. The findings from this study suggest that the aqueous extract of these leaves may be prescribed as adjunct to dietary therapy and drug treatment for controlling diabetes mellitus.     

Antidiabetic activity and toxicity of Zizyphus spina-christi leaves

The effect of the butanol extract of Zizyphus spina-christi (L.), Willd (Rhamnaceae) leaves and its major saponin glycoside, christinin-A, on the serum glucose and insulin levels was studied in non-diabetic control, type-I (insulin-dependent) and type-II (non-insulin-dependent) diabetic rats. Pretreatment either with 100 mg/kg butanol extract or christinin-A potentiated glucose-induced insulin release in non-diabetic control rats. In type-II but not in type-I diabetic rats pretreatment with the butanol extract or christinin-A improved the oral glucose tolerance and potentiated glucose-induced insulin release. Treatment either with 100 mg/kg butanol extract or christinin-A reduced the serum glucose level and increased the serum insulin level of non-diabetic control and type-II diabetic rats but not of type-I diabetic rats. Effects of the butanol extract and christinin-A were similar. Pretreatment of non-diabetic control and type-II diabetic rats either with 100 mg/kg butanol extract or christinin-A enhanced the glucose lowering and insulinotropic effects of 5 g/kg glibenclamide. The hyperglycemic and hypoinsulinemic effects of 30 mg/kg diazoxide in non-diabetic control and type-II diabetic rats were inhibited and antagonized, respectively by pretreatment with the butanol extract or christinin-A. The relaxant effects of different concentrations of diazoxide on the isolated norepinephrine-contracted aortic strips were inhibited by 100 micromol/l christinin-A or 10 micromol/l glibenclamide. The combination of glibenclamide and christinin-A led to complete inhibition of the relaxant effects of different concentrations of diazoxide. At a dose level much higher than that required to produce satisfactory insulinotropic and hypoglycemic effects, the butanol extract of Zizyphus spina-christi leaves produced a depressant effect on the central nervous system in rats. Treatment of rats with 100mg/kg butanol extract for 3 months produced no functional or structural disturbances in liver and kidney and no haematological changes. In addition, the oral LD50 of the butanol extract in mice was 3820 mg/kg, while that of glibenclamide was 3160 mg/kg. Thus, Zizyphusspina-christi leaves appears to be a safe alternative to lower blood glucose. The safe insulinotropic and subsequent hypoglycemic effects of Zizyphus spina-christi leaves may be due to a sulfonylurea-like activity.     

Hypoglycemic effect of extracts and fractions from Psacalium decompositum in healthy and alloxan-diabetic mice

The hypoglycemic effect of the hexane, methanol and water extracts obtained from roots of Psacalium decompositum (Asteraceae) was investigated in fasting healthy mice. Only the water extract significantly reduced blood glucose in a dose-dependent manner in normal mice after intraperitoneal administration (P<0.05). This water extract was macerated with methanol obtaining a precipitate (WMP fraction), and it was studied in healthy and alloxan-diabetic mice. The WMP fraction showed significant hypoglycemic activity in healthy and mild diabetic mice, but the administration of this fraction to animals with severe diabetes did not cause any significant decrease in blood glucose levels. Two polysaccharide components isolated from WMP fraction showed hypoglycemic effect when tested in healthy mice.     

Hypoglycaemic action of the flavonoid fraction of Cuminum nigrum seeds

The seeds of Cuminum nigrum were screened phytochemically and were found to contain 8% flavonoids and 0.01% alkaloids. When studied for their effect on blood glucose levels, oral administration of the flavonoid contents of the plant caused a hypoglycaemic effect at a dose range of 0.5 to 1.5 g/kg, both in normal and alloxan-diabetic rabbits. The hypoglycaemic effect started 2 h after drug administration, reaching a maximum within 4-8 h and the blood glucose levels returned close to normal within 24 h of drug administration. The glibenclamide (5 mg/kg), produced a hypoglycaemic effect in the normal rabbits, whereas it had no effect on the blood glucose levels of alloxan-diabetic rabbits. The alkaloids isolated from C. nigrum seeds, however, failed to exert any significant hypoglycaemic effect in either the normal or diabetic rabbits. A 7 day acute toxicity study in rabbits did not produce any apparent adverse effect at doses as high as 5 g/kg orally. These data indicate that the total flavonoid contents of C. nigrum seeds exhibited considerable hypoglycaemic activity in rabbits and may therefore be responsible for the previously reported antidiabetic activity of the seeds. Furthermore, it is conceivable that the C. nigrum flavonoids possess insulin triggering and/or insulin-like properties.     

Effect of crude extract and fractions from Vitex megapotamica leaves on hyperglycemia in alloxan-diabetic rats

The effect of the crude extract, ethyl acetate and n-butanol fractions from Vitex megapotamica (Spreng) Moldenke on glycemia was investigated in diabetic rats. Oral administration of crude extract significantly reduced serum glucose levels in both normal and diabetic animals. In normal rats, serum glucose lowering was observed with 400 and 800 mg/kg at 2 and 2-3h, respectively after oral crude extract treatment. Nevertheless, the hypoglycemic effect of Vitex megapotamica in diabetic rats was evident at 1 and 2h and from 1 to 3h after treatment with 400 and 800 mg/kg, respectively. The ethyl acetate as well as n-butanol fractions were able to diminish glycemia in diabetic animals. The ethyl acetate fraction (400 and 800 mg/kg) produced the maximum hypoglycemic effect (28 and 20%, respectively) in diabetic rats and the same dose of the n-butanol fraction reduced the hyperglycemia only by 11% at 1h after treatment. Additionally, in hyperglycemic normal rats neither crude extract nor ethyl acetate fraction modified the glucose tolerance and the known tolbutamide effect on insulin release was clearly observed in this group. Thus, this study shows that Vitex megapotamica has an anti-hyperglycemic action, is able to ameliorate the diabetic state and, probably, is a source of hypoglycemic compounds.     

Assessment of antidiabetic potential of Cynodon dactylon extract in streptozotocin diabetic rats

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extract of Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administration of aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000mg/kg bw of aqueous extract of Cynodon dactylon were evaluated and the dose of 500mg/kg was identified as the most effective dose. It lowers blood glucose level around 31% after 4h of administration in normal rats. The same dose of 500mg/kg produced a fall of 23% in blood glucose level within 1h during glucose tolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250mg/kg bw). Severely diabetic rats were also treated daily with 500mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level. A reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic potential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, in severely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueous extract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.     

Effect of Cassia auriculata Linn. on serum glucose level,glucose utilization by isolated rat hemidiaphragm

An aqueous leaf extract of Cassia auriculata (C. auriculata) was found to lower the serum glucose level in normal rats. Maximum reduction in serum glucose level was observed after 4 h at a dose levels of 100, 200, 400 mg/kg body weight of the extract. In normal rats the serum glucose level reduction at 4th h was 23% by 100 mg/kg body weight and 31% by 200 mg/kg body weight. In alloxan-induced diabetic rats, chronic administration of the extract significantly reduced the serum glucose level from third day to till the end of the experiment. The extract was also found to inhibit the body weight reduction induced by alloxan administration. Glucose uptake and glycogen deposition studies suggest that C. auriculata leaf extract probably has no direct insulin like effect which can enhance the peripheral utilization of glucose.     

Probable mechanism of hypoglycemic activity of bassic acid, a natural product isolated from Bumelia sartorum

Bassic acid, an unsaturated triterpene acid isolated from an ethanol extract of Bumelia sartorum rootbark, elicited significant hypoglycemic activity in alloxan-diabetic rats and altered the pattern of glucose tolerance in these animals. In addition, bassic acid treatment increased significantly the glucose uptake process and glycogen synthesis in isolated rat diaphragm. Bassic acid treatment increased plasma insulin levels significantly in alloxan-diabetic rats. It is suggested that the hypoglycemia activity of bassic acid may be mediated through enhanced secretion of insulin from the pancreatic beta-cells.     

Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus.

Salvia fruticosa Mill. has a folk reputation in the eastern Mediterranean region as a hypoglycemic agent. In order to confirm this claim, a 10% infusion of its leaves was tested, at an oral dose of 0.250 g/kg b.w.t., on normoglycemic rabbits and in rabbits made hyperglycemic by alloxan administration. This oral dose caused a statistically significant reduction in blood glucose levels in alloxanhyperglycemic rabbits, but not in normoglycemic animals, only after repeated administrations of the infusion (once a day for 7 consecutive days). Instead, the hypoglycemic effect was evoked by single oral doses of infusion in both normoglycemic and alloxanhyperglycemic rabbits orally loaded with glucose. However, in these animals S. fruticosa infusion did not modify plasma insulin levels. Moreover, the hypoglycemic effect of the drug was not evoked in rabbits which received the glucose load intravenously. These data strongly suggest that S. fruticosa treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose.     

Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits

The hypoglycaemic and hypolipidemic effect of ethanolic extract obtained from seeds of E. jambolana was investigated in alloxan-induced diabetic rabbits. Hypoglycaemic activity was assessed by reduction in fasting blood glucose (FBG) at 90min and also fall in peak blood glucose during glucose tolerance test (GTT) in sub-diabetic and mild diabetic (MD) rabbits, but in severe diabetic (SD) rabbits by reduction in FBG at 90min. Ethanolic extract (100mg/kg body weight) when given orally to sub-diabetic (AR) for 1 day, MD for 7 days and SD for 15 days showed significant fall in FBG at 90min (12% AR, 18.9% MD and 29% SD) and also produced 16.9% fall in peak blood glucose in AR and 21% in MD rabbits during GTT. When administered daily for 15 days to MD and SD rabbits, significant fall in FBG (41.3% MD, 31.6% SD) and glycosylated haemoglobin (GHb) levels (23.3% MD, 26.6% SD) were observed, while serum insulin level showed significant increase (32.8% MD, 26.9% SD). Liver and muscle glycogen content also increased. The ethanolic extract of seeds also exhibited significant hypolipidemic effect as evident from fall in total serum cholesterol (TC)/high density lipoprotein cholesterol (HDL-c) ratio, serum low density lipoprotein cholesterol (LDL-c) levels and decreased activity of HMG-CoA reductase. The histopathological studies of liver, pancreas and aorta in alcoholic extract treated diabetic groups revealed almost normal appearance.     

Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal and diabetic rats

The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZ-induced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body (plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the diabetic controls. Our results suggest that yacon water extract produces an increase in plasma insulin concentration.     

Hypoglycemic activity of Artemisia herba alba

Artemisia herba alba has been widely used in Iraqi folk medicine for the treatment of diabetes mellitus. Oral administration of an aqueous extract (0.39 g/kg) of the aerial parts of this plant to normoglycemic and to alloxan-diabetic rabbits produced significant hypoglycemic activity, which was consistent and time-dependent.     

Effect of aloes on blood glucose levels in normal and alloxan diabetic mice

The acute and chronic effects of the exudate of Aloe barbadensis leaves and its bitter principle were studied on plasma glucose levels of alloxan-diabetic mice. Aloes was administered orally, 500 mg/kg, and the bitter principle was administered intraperitoneally, 5 mg/kg. The hypoglycemic effect of a single oral dose of aloes on serum glucose level was insignificant whereas that of the bitter principle was very highly significant and extended over a period of 24 h with maximum hypoglycemia observed at +8 h. In chronic studies, aloes was administered twice daily and the bitter principle was administered once a day for 4 days. The maximum reduction in plasma glucose level was observed at the 5th day in both cases. The hypoglycemic effect of aloes and its bitter principle may be mediated through stimulating synthesis and/or release of insulin from the beta-cells of Langerhans.     

Effect of Hibiscus rosa sinensis Linn. ethanol flower extract on blood glucose and lipid profile in streptozotocin induced diabetes in rats

Blood glucose and total lipid levels were determined in streptozotocin induced diabetic rats after oral administration of an ethanol flower extract of Hibiscus rosa sinensis. A comparable hypoglycemic effect was evidenced from the data obtained after 7 and 21 days of oral administration of the extract and glibenclamide. Maximal diminution in blood glucose (41-46%) and insulin level (14%) was noticed after 21 days. The extract lowered the total cholesterol and serum triglycerides by 22 and 30%, respectively. The increase in HDL-cholesterol was much higher (12%) under the influence of the extract as compared to that of glibenclamide (1%). The hypoglycemic activity of this extract is comparable to that of glibenclamide but is not mediated through insulin release. Other possible mechanisms are discussed.     

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.     

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.     

Hypoglycemic effect of Equisetum myriochaetum aerial parts on type 2 diabetic patients

The hypoglycemic effect of a water extract from aerial parts (0.33 g/kg) of Equisetum myriochaetum Schlecht and Cham (Equisetaceae) was analyzed in 11 recently diagnosed type 2 diabetic patients. A single dose of this extract was orally administered. Glucose and insulin were determined at 0, 30, 60, 90,120 and 180 min after administration. The same patients served as the control group and received only colored water as placebo. The administration of the extract significantly reduced the blood glucose levels of the type 2 diabetic patients within 90, 120 and 180 min. There were no significant changes in the insulin levels. The results demonstrate that the water extract of the aerial parts of E. myriochaetum shows a hypoglycemic effect in type 2 diabetic patients starting 90 min after its administration.