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1.  Methanolic leaf exctract of Otostegia integrifolia Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents 
Background
Although the leaves of Otostegia integrifolia traditionally claimed in Ethiopian folklore medicine for management of diabetes mellitus, it has not been validated. The aim of this study was therefore to investigate the antidiabetic activity of Otostegia integrifolia in rodents.
Methods
Male rats or mice were randomly divided into five groups for diabetic, hypoglycemic and glucose tolerance test (OGTT) studies. In all models, group I received Tween 80, 2% v/v, Group II (GL5) treated with 5 mg/kg of glibenclamide and the remaining group: III, IV and V were given the plant extract at doses of 100 mg/kg 200 mg/kg and 400 mg/kg respectively. Blood glucose levels (BGL) were measured by collecting blood samples at different time points. Data was analyzed using one way ANOVA followed by Dunnet’s post hoc test to carry out between and within group comparisons. P < 0.05 was considered as statistically significant.
Results
Inter-group analysis revealed that O. integrifolia at 100 mg/kg and 200 mg/kg reduced the 4th hour fasting blood BGL significantly (p < 0.001) compared to the control group. The intra-group analysis result has shown O. integrifolia at 200 mg/kg produced a significant (p < 0.05) reduction in BGL at the 1st, 2nd, 3rd and 4th hours of post treatment compared to their respective initial levels. Moreover, in the hypoglycemic and OGTT models, O. integrifolia extract at 200 mg/kg, has shown a significant reduction in blood glucose levels compared to negative controls and across all time points.
Conclusion
The crude extract of O. integrifolia has shown significant antidiabetic, hypoglyceamic and oral glucose tolerating effects. The effective dose of the extract was found to be 200 mg/kg in time dependent manner.
doi:10.1186/s12906-015-0535-5
PMCID: PMC4321712
Diabetes mellitus; Otostegia integrifolia; Streptozotoicn; Mice; Rats; Ethiopia
2.  Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats 
Background
Terminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats.
Methods
The blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test.
Results
The chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated.
Conclusion
The present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects.
doi:10.1186/1472-6882-6-17
PMCID: PMC1540439  PMID: 16677399
3.  Evaluation of Antidiabetic Activity of Hydroalcoholic Extract of Cestrum nocturnum Leaves in Streptozotocin-Induced Diabetic Rats 
Objective. To investigate antidiabetic activity of hydroalcoholic extract of Cestrum nocturnum leaves in Wistar rats. Method. Cestrum nocturnum leaves extract in hydroalcoholic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Wistar rats were made diabetic by a single dose of streptozotocin (150 mg/kg i.p.). Hydroalcoholic leaves extract of Cestrum nocturnum was screened for antidiabetic activity and given to the STZ-induced diabetic rats at a concentration of 200 mg/kg and 400 mg/kg of body weight in different groups of 6 diabetic rats each orally once a day for 15 days. Metformin is also given to another group to support the result at a dose of 10 mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of rats were measured on 0, 5, 7, and 15th days. Results. Oral administration of the extracts for 15 days caused a significant (P < 0.01) reduction in blood glucose levels in diabetic rats. The body weight of diabetic animals was also improved after daily administration of extracts. The extract also improved other altered biochemical parameters associated with diabetes. Also the changes in food intake, water intake, and weight of internal organs were also restored to normal by the prolonged effect of extract treatment.
doi:10.1155/2013/150401
PMCID: PMC3787616  PMID: 24151502
4.  Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats 
The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 μg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug.
doi:10.4103/0974-7788.76780
PMCID: PMC3059439  PMID: 21455444
Acute toxicity; alloxan; antidiabetic activity; Pongamia pinnata
5.  Effect of ethanolic extract of Cassia occidentalis Linn. for the management of alloxan-induced diabetic rats 
Pharmacognosy Research  2010;2(3):132-137.
Aim:
As per traditional claims, root, bark, leaf and flower of the plant Cassia occidentalis Linn. (Caesalpiniaceae) have been reported to possess antidiabetic activity. Based on this traditional indication, the aim of this study was to evaluate the antidiabetic activity of ethanolic extract of C. occidentalis in normal and alloxan induced diabetic rats.
Materials and Methods:
Ethanolic extract of the whole plant of C. occidentalis was orally tested at doses of 100 and 200 mg/kg for evaluating the hypoglycemic effect in normal and alloxan-induced diabetic rats. In addition, changes in body weight, serum cholesterol, triglyceride and total protein levels, assessed in the ethanol extract treated diabetic rats were compared with diabetic control and normal animals. Histopathologic observations during 21 days of treatment were also evaluated.
Results:
Ethanolic extract of C. occidentalis produced a significant reduction in fasting blood glucose levels in the normal and alloxan-induced diabetic rats at doses of 100 and 200 mg/kg body weight. Treatment with ethanolic extract of C. occidentalis in normal and alloxan-induced diabetic rats led to a dose-dependent fall in blood sugar levels. Significant differences were observed in serum lipid profiles (cholesterol and triglyceride), serum protein and changes in body weight in ethanolic extract treated diabetic animals, when compared with the diabetic control and normal animals. Concurrent histopathologic studies of the pancreas of these animals showed comparable regeneration by ethanolic extract, which were earlier necrosed by alloxan.
Conclusion:
Ethanolic extract of C. occidentalis exhibited significant antidiabetic activity in normal and alloxan-induced diabetic rats. The rats also showed improvement in parameters like body weight and lipid profiles and also, histopathologic studies showed regeneration of β-cells of pancreas and so it might be of value in the treatment of diabetes.
doi:10.4103/0974-8490.65506
PMCID: PMC3141303  PMID: 21808555
Antidiabetic activity; Cassia occidentalis; histopathology; alloxan
6.  Antidiabetic and hypolipidemic activities of ethanolic leaf extract and fractions of Melanthera scandens 
Objective
To evaluate the antidiabetic and hypolipidemic activities of ethanolic leaf extract and fraction of Melanthera scandens (M. scandens) in alloxan-induced diabetic rats.
Methods
M. scandens leaf extract/fractions (37–111 mg/kg) were administered to alloxan-induced diabetic rats for 14 days and blood glucose levels (BGL) of the diabetic rats were monitored at intervals of 7 hours for acute study and 14 days for prolonged study. Lipid profiles of the treated diabetic rats were determined after the period of treatment.
Results
Treatment of alloxan-induced diabetic rats with the extract/fractions caused a significant (P<0.001) reduction in fasting bloodglucose levels (BGL) of the diabetic rats both in acute study and prolonged treatment (2 weeks). The activities of the extract and fractions were more than that of the reference drug, glibenclamide. The extract/fractions exerted a significant reduction in the levels of serum total cholesterol, triglycerides, LDL and VLDL of extract with increases in HDL levels of the diabetic rats.
Conclusions
These results suggest that the leaf extract/fractions of M. scandens possesses antidiabetic effect on alloxan induced diabetic rats and this justifies its use in ethno medicine and can be exploited in the management of diabetes.
doi:10.1016/S2221-1691(12)60089-6
PMCID: PMC3609341  PMID: 23569963
Antidiabetic; Hypolididemic; Melanthera scandens
7.  Protective effect of aqueous extract of seed of Psoralea corylifolia (Somraji) and seed of Trigonella foenum-graecum L. (Methi) in streptozotocin-induced diabetic rat: A comparative evaluation 
Pharmacognosy Research  2013;5(4):277-285.
Background:
Psoralea corylifolia (Somraji) and Trigonella foenum-graecum L. (Methi), important medicinal plants widely used in India as folk medicine. Local people of West Bengal traditionally used the seeds of these plants to cure diabetes.
Objective:
Present study was designed to investigate the antidiabetic efficacy of aqueous extract of seeds of these plants in separate or in composite manner in streptozotocin (STZ)-induced diabetic rat.
Materials and Methods:
Diabetes was induced by intramuscular injection of STZ at the dose of 40 mg/ml of citrate buffer/kg body weight. Fasting blood glucose (FBG), glyclated hemoglobin (HbA1C) and activities of hexokinase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase of liver in experimental animals were assessed. Hyperlipidemic state developed in the experimental diabetic rat was assessed by measuring the levels of total cholesterol, triglyceride, and lipoproteins in serum.
Results:
There was significant increased in the levels of FBG, HbA1C and lipid profiles along with diminution (P < 0.001) in the activities of hepatic hexokinase, glucose-6-phosphate dehydrogenase and elevation in glucose-6-phosphatase in diabetic control animals in respect to the untreated control. Significant recovery (P < 0.05) in the activities of above mentioned enzymes along with the correction in the levels of FBG, HbA1C and serum lipid profiles were noted towards the control level after the treatment of composite extract (i.e. 100 mg of Somraji: 100 mg of Methi, total 200 mg/kg body weight) than the individual extract (i.e. 200 mg of Somraji or 200 mg of Methi, per kg body weight) treatment.
Conclusion:
Results suggest that composite extract of above plant parts has more potent antidiabetic efficacy than the individual extract.
doi:10.4103/0974-8490.118840
PMCID: PMC3807993  PMID: 24174822
Carbohydrate metabolic enzymes; glycogen; lipid profiles; streptozotocin
8.  Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in alloxan induced diabetic rats 
Indian Journal of Pharmacology  2011;43(4):455-459.
Objective:
To evaluate the antidiabetic activity of ethanolic extract of Dioscorea alata in glucose loaded and alloxan induced diabetic rats.
Materials and Methods:
The authenticated tubers of D. alata (DA) (JSSCPDP/2008/157) were collected from Dharmapuri, Tamil Nadu. The ethanol extract was tested for hypoglycemic activity in normal rats. In oral glucose tolerance test, glucose (3 g/kg, p.o.) was administered to non diabetic control, metformin (250 mg/kg, p.o.) and DA extract (100 and 200 mg/kg, p.o.) to treat treated rats. Diabetes mellitus was induced by alloxan monohydrate (120 mg/kg, i.p.) in physiological saline after overnight fasting for 18 hours. DA extract (100 and 200 mg/kg, p.o.) and standard drug metformin (250 mg/kg, p.o.) were administered to diabetic rats for 21 days. Fasting blood glucose level and changes in body weight were measured on days 0, 7, 14, and 21. At the end of 21st day, serum lipid profile, total protein, albumin, and creatinine were assessed.
Results:
In glucose loaded normal rats, the treatment with the extract of DA had shown a highly significant reduction (P < 0.001) in blood glucose levels at the doses of 100 and 200 mg/kg, respectively. The extract did not produce hypoglycemic activity at both the dose levels in normal, fasted rats. In alloxan induced diabetic rats, the body weight of the DA extract treated animals had shown a significant increase (P < 0.001) after 21 days treatment. The blood glucose level was reduced significantly by 47.48% and 52.09% after 21 days treatment at dose levels 100 and 200 mg/kg, respectively. Serum lipid levels, total protein, albumin, and creatinine were reversed toward near normal in treated rats as compared to diabetic control.
Conclusion:
The results indicate that ethanol extract of DA tubers possesses significant antidiabetic activity.
doi:10.4103/0253-7613.83121
PMCID: PMC3153713  PMID: 21845005
Antihyperglycemic; alloxan; Dioscorea alata; diabetes mellitus; oral glucose tolerance test
9.  A study of antimicrobial activity, acute toxicity and cytoprotective effect of a polyherbal extract in a rat ethanol-HCl gastric ulcer model 
BMC Research Notes  2012;5:546.
Background
The decoction of the aerial parts of Rhynchosia recinosa (A.Rich.) Bak. [Fabaceae] is used in combination with the stem barks of Ozoroa insignis Del. (Anacardiaceae), Maytenus senegalensis (Lam.) Excell. [Celastraceae] Entada abyssinica Steud. ex A.Rich [Fabaceae] and Lannea schimperi (Hochst.)Engl. [Anacardiaceae] as a traditional remedy for managing peptic ulcers. However, the safety and efficacy of this polyherbal preparation has not been evaluated. This study reports on the phytochemical profile and some biological activities of the individual plant extracts and a combination of extracts of the five plants.
Methods
A mixture of 80% ethanol extracts of R. recinosa, O. insignis, M. senegalensis, E. abyssinica and L. schimperi at doses of 100, 200, 400 and 800 mg/kg body wt were evaluated for ability to protect Sprague Dawley rats from gastric ulceration by an ethanol-HCl mixture. Cytoprotective effect was assessed by comparison with a negative control group given 1% tween 80 in normal saline and a positive control group given 40 mg/kg body wt pantoprazole. The individual extracts and their combinations were also tested for antibacterial activity against four Gram negative bacteria; Escherichia coli (ATCC 25922), Salmonella typhi (NCTC 8385), Vibrio cholerae (clinical isolate), and Klebsiella pneumoniae (clinical isolate) using the microdilution method. In addition the extracts were evaluated for brine shrimp toxicity and acute toxicity in mice. Phytochemical tests were done using standard methods to determine the presence of tannins, saponins, steroids, cardiac glycosides, flavonoids, alkaloids and terpenoids in the individual plant extracts and in the mixed extract of the five plants.
Results
The combined ethanolic extracts of the 5 plants caused a dose-dependent protection against ethanol/HCl induced ulceration of rat gastric mucosa, reaching 81.7% mean protection as compared to 87.5% protection by 40 mg/kg body wt pantoprazole. Both the individual plant extracts and the mixed extracts of 5 plants exhibited weak to moderate antibacterial activity against four G-ve bacteria. Despite Ozoroa insignis being toxic to mice at doses above 1000 mg/kg body wt, the other plant extracts and the combined extract of the 5 plants were tolerated by mice up to 5000 mg/kg body wt. The brine shrimp test results showed the same pattern of toxicity with Ozoroa insignis being the most toxic (LC50 = 10.63 μg/ml). Phytochemical tests showed that the combined extract of the five plants contained tannins, saponins, steroids, cardiac glycosides, flavonoids and terpenoids. Flavonoids, tannins and terpenoids are known to have antioxidant activity.
Conclusion
The combined extract of the five plants exhibited a dose-dependent protective activity in the rat ethanol-HCl gastric ulcer model. The extracts also exhibited weak antibacterial activity against four Gram negative bacteria and low acute toxicity in mice and brine shrimps. Although the results support claims by traditional healers who use a decoction of the five plants for treatment of peptic ulcers, more models of gastric ulceration and proper animal toxicity studies are needed to validate possible clinical use of the polyherbal extract. It is also evident that the doses of the crude extracts showing protection of the gastric mucosa are too large for realistic translation to direct clinical application, but further studies using bioassay guided fractionation are important to either identify more practical fractions or active compound/s.
doi:10.1186/1756-0500-5-546
PMCID: PMC3532137  PMID: 23031266
Ozoroa insignis; Maytenus senegalensis; Entada abyssinica; Lannea schimperi; Gastroprotection; Toxicity
10.  Effect ofOcimum sanctum (Tulsi) and vitamin E on biochemical parameters and retinopathy in streptozotocin induced diabetic rats 
This study was carried out to see the effect of the aqueous extract ofOcitum sanctum Linn (Tulsi) with Vitamin E on biochemical parameters and retinopathy in the streptozotocin-induced diabetic albino male rats. Adult albino male rats weighing 150–200 gm were made diabetic by intraperitoneal injection of streptozotocin in the dose 60 mg/kg in citrate buffer (pH 6.3). The diabetic animals were left for one month to develop retinopathy. Biochemical parameters like plasma glucose, oral glucose tolerance and glycosylated hemoglobin HbA1c, were measured along with lipid profile, and enzymes like glutathione peroxidase (GPX), lipid peroxidase (LPO), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) in normal, untreated diabetic rats and diabetic rats treated withOcimum sanctum L extracts and vitamin E. Fluorescein angiography test was done for assessing retinopathy. Results on biochemical parameters were analyzed statistically by using ANOVA followed by Dunnet's ‘t’-test. A p-value of <0.05 was considered as significant. Evaluation of biochemical profile in treated groups showed statistically significant reduction in plasma levels of glucose, HbA1c, lipid profile and LPO, and elevation of GPX, SOD, CAT and GST. Treatment of the diabetic animals withOcimum sanctum and Vitamin E, alone and in combination for 16 weeks showed reversal of most of the parameters studied including plasma glucose levels. Angiography showed improvement in retinal changes following combined antidiabetic treatment.
doi:10.1007/BF02912939
PMCID: PMC3453971  PMID: 23105641
Ocimum sanctum; Vitamin E; Diabetes mellitus; Diabetic retinopathy; Lipid peroxidation; Antioxidants
11.  Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity 
Pharmacognosy Research  2014;6(2):180-187.
Background:
Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control.
Objective:
The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI).
Materials and Methods:
Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed.
Results:
There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity.
Conclusion:
These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress.
doi:10.4103/0974-8490.129043
PMCID: PMC3996756  PMID: 24761124
Alloxan; antioxidant activity; 1, 1- diphenyl-2-picrylhydrazyl; hyperglycemia; metformin hydrochloride; oxidative stress
12.  Hypoglycemic Effects of Three Medicinal Plants in Experimental Diabetes: Inhibition of Rat Intestinal α-glucosidase and Enhanced Pancreatic Insulin and Cardiac Glut-4 mRNAs Expression 
Garlic (Allium sativum L., Alliaceae), Persian shallot (Allium ascalonicum L., Alliaceae ) and Sage (Salvia officinalis L., Lamiaceae) are believed to have hypoglycemic properties and have been used traditionally as antidiabetic herbal medicines in Iran. In this study, diabetes was induced by subcutaneous injection of alloxan monohydrate (100 mg kg−1) to male Wistar rats. Antidiabetic effects of methanolic extracts of the above mentioned three plants on alloxan-diabetic rats was investigated in comparison with the effects of antidiabetic drugs such as acarbose, glibenclamide and metformin by measuring postprandial blood glucose (PBG), oral glucose tolerance test (OGTT), inhibition of rat intestinal α-glucosidase enzymes activities and pancreatic Insulin and cardiac Glut-4 mRNAs expression. In short term period, hypoglycemic effects of A. sativum and A. ascalonicum showed significant reduction of PBG similar to glibenclamide (5 mg kg−1 bw) while S. officinalis significantly reduced PBG similar to acarbose (20 mg kg−1 bw). After 3 weeks of treatment by methanolic plant extracts, significant chronic decrease in the PBG was observed similar to metformin (100 mg kg−1 bw). For OGTT, S. officinalis reduced PBG in a similar way as acarbose (20 mg kg−1 bw). Intestinal sucrase and maltase activities were inhibited significantly by A. sativum, A. ascalonicum and S. officinalis. In addition, we observed increased expression of Insulin and Glut-4 genes in diabetic rats treated with these plants extracts. Up regulation of Insulin and Glut-4 genes expression and inhibition of α-glucosidaseactivities are the two mechanisms that play a considerable role in hypoglycemic action of garlic, shallot and sage.
PMCID: PMC3813273  PMID: 24250646
Diabetes; Glut-4; Insulin; OGTT; PBG
13.  Antioxidant potential of the methanol–methylene chloride extract of Terminalia glaucescens leaves on mice liver in streptozotocin-induced stress 
Indian Journal of Pharmacology  2008;40(6):266-270.
Aim:
The antioxidant effect of the methanol–methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress.
Methods:
Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded.
Results:
In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase.
Conclusion:
These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.
doi:10.4103/0253-7613.45153
PMCID: PMC3025144  PMID: 21279183
Antioxidant enzymes; diabetes mellitus; malondialdehyde; Terminalia glaucescens
14.  Trichosanthes cucumerina Linn. improves glucose tolerance and tissue glycogen in non insulin dependent diabetes mellitus induced rats 
Indian Journal of Pharmacology  2008;40(3):103-106.
Objective:
To study the effect of Trichosanthes cucumerina Linn. on non insulin dependent diabetes mellitus induced rats.
Materials and Methods:
Non Insulin Dependent Diabetes Mellitus (NIDDM) was induced by administering streptozotocin (90 mg/kg, i.p.) in neonatal rat model. NIDDM animals were treated with aqueous extract of Trichosanthes cucumerina (100 mg/kg/day) orally for six weeks. Parameters such as fasting blood glucose, Oral Glucose Tolerance Test (OGTT) and tissue glycogen content were evaluated.
Results:
Aqueous extract of Trichosanthes cucumerina significantly (P<0.01) decreased the elevated blood glucose of NIDDM induced rats. OGTT of NIDDM animals showed glucose intolerance. Blood glucose of diabetic animals reached peak at 45 min and remains high even after 2h. In case of Trichosanthes cucumerina treated group, the blood glucose reached peak level at 30 min, followed by decrease in glucose level up to 2h. The drug has significantly (P<0.01) reduced the postprandial blood glucose of diabetic animals. Glycogen content of insulin dependent tissues such as liver and skeletal muscle was found to be improved by 62% and 58.8% respectively with Trichosanthes cucumerina as compared to NIDDM control.
Conclusion:
Studies revealed that, Trichosanthes cucumerina possess antidiabetic activity. The drug improved the oral glucose tolerance of NIDDM subjects. Increase in tissue glycogen content indicates the effect of the drug on the uptake of glucose by the peripheral tissues to reduce insulin resistance of NIDDM.
doi:10.4103/0253-7613.42301
PMCID: PMC2792599  PMID: 20040935
Glycogen; Non Insulin Dependent Diabetes Mellitus; oral glucose tolerance test; Trichosanthes cucumerina
15.  Evaluation of the Antidiabetic and Antilipaemic Activities of the Hydroalcoholic Extract of Phoenix Dactylifera Palm Leaves and Its Fractions in Alloxan-Induced Diabetic Rats 
Background:
The antidiabetic and antilipaemic effects of Phoenix dactylifera leaf extract (PDE) and its fractions were investigated in various rat models.
Methods:
Diabetes was induced in male Wistar rats by alloxan monohydrate. Diabetic animals were randomly divided into 8 groups (1 diabetic control and 7 treated groups). Diabetic control animals received saline (5 mL/kg) orally, whereas the treatment groups received different doses of PDE (100, 200, and 400 mg/kg), PDE fractions (50, 100, and 200 mg/kg), or glibenclamide (4 mg/kg) orally once a day for 14 days. Blood was withdrawn for glucose determination on the 1st, 6th, 10th, and 14th days. The rats were fasted overnight and then sacrificed on the 14th day; blood was collected for biochemical evaluation, including the levels of blood glucose, plasma insulin, serum triglyceride, and cholesterol.
Results:
Subacute administration of PDE or its fractions in alloxan-induced diabetic rats significantly reduced blood glucose (P < 0.01). Water intake, serum triglyceride, and cholesterol also decreased in treated animals compared with the control group (P < 0.01). Plasma insulin level increased in the treated groups relative to the control group (P < 0.01).
Conclusion:
The results suggested that PDE exhibits antidiabetic and antilipaemic effects in alloxan-induced diabetic rats.
PMCID: PMC3216186  PMID: 22135555
antidiabetics; antilipaemics; antioxidants; diabetes metabolism; plant extracts
16.  Antihyperglycemic Activity of Petroleum Ether Leaf Extract of Ficus krishnae L. on Alloxan-induced Diabetic Rats 
The petroleum ether leaf extract of Ficus krishnae has been evaluated for the management of diabetes in alloxan induced diabetic rats. Phytochemical screening of the leaf extract for various chemical compounds has also been carried out. Leaf extract was administered continuously for 21 days orally at a dose of 200 mg/kg. Along with this, the blood glucose level was monitored at regular intervals to understand the activity of the extract. The leaf extract has decreased the blood glucose level of diabetic rats which was comparable to an antidiabetic standard drug, glibenclamide, given at a dose of 2.5 mg/kg. It has been observed that the leaves of Ficus krishnae possess antidiabetic activity and it reduces the blood glucose level significantly. The phytochemical screening of leaf has revealed the presence of carbohydrates, flavonoids, tannins, glycosides, terpenoids, steroids, alkaloids, gums and mucilage, phlobatannins, reducing sugars and phenolic compounds. The Fourier Transform Infrared analysis of glibenclamide and leaf powder has displayed some common absorption spectra. This shows that leaf powder has a molecule which is close to glibenclamide. Wavelength Dispersive X-Ray Fluorescence spectroscopy have shown the presence of cellulose, Ca, Si, K, Cl, Mg, P, S, Al, Fe, Na, Sr, Pd, Zn, Mn, Cr, Mo, Br, Ni, Rb and Zr. It is assumed that these elements alongwith other chemical compounds of the plant species may play a role in the management of diabetes. The Raman Specta of both glibenclamide and leaf powder has also shown some similarities. The results obtained during the present investigation have revealed the antidiabetic activity of Ficus krishnae leaves. The phytochemical screening has indicated the various chemical constituents likely to be responsible for this activity. The Fourier Transform Infrared, Wavelength Dispersive X-Ray Fluorescence and Raman Specta of the leaf powder suggested that there is some glibenclamide like molecule or its derivatives which is imparting antidiabetic activity.
PMCID: PMC4171869  PMID: 25284930
Diabetes; Ficus krishnae; glibenclamide; phytochemicals; FTIR; WD-XRF; Raman spectroscopy
17.  Effects of methanolic and butanolic fractions of Allium elburzense Wendelbo bulbs on blood glucose level of normal and STZ-induced diabetic rats 
Allium elburzense (A. elborzense, Alliaceae), a plant rich in saponins, is an edible vegetable in northern Iran with a folk background use as antidiabetic which has not yet been examined for this indication. To evaluate the antidiabetic potential of A. elburzense, its hydroalcoholic (HdAE) and butanolic extracts (BuE) were examined. The acute (1, 2, 3, 4, 8 h) and sub-acute (11 days) effects of oral (p.o.) and intraperitoneal (i.p.) administration of HdAE and BuE of A. elburzense bulbs in different doses were evaluated on blood glucose levels of normal and streptozotocin (STZ, 55 mg/kg body weight)-induced diabetic rats. Glibenclamide (1 mg/kg b.w.) was used as reference drug. Sub-acute treatment with HdAE for 11 days reduced significantly blood glucose levels in diabetic rats (at least P<0.05), while BuE was effective only following i.p. administration (P<0.01). Acute administration did not reduce blood glucose level in normal and diabetic animals. It is concluded that HdAE of A. elburzense exhibited a significant antihyperglycemic activity following chronic administration. These results provide evidence for potential use of A. elburzense in diabetes mellitus considering the fact that this plant is endemic to a location of Iran where diabetes is a high prevalence disorder.
PMCID: PMC3523411  PMID: 23248670
Allium elburzenses; Diabetes mellitus; Antidiabetic; Plant extract; Streptozotocin
18.  Evaluation of in vivo antitrypanosomal activity of crude extracts of Artemisia abyssinica against aTrypanosoma congolense isolate 
Background
African trypanosomiasis is a major disease of economic and public health importance affecting agricultural and human development. The search for alternative compounds against African trypanosomiasis is justified by various limitations of existing chemotherapeutic agents. This study was aimed at screening the hydromethanolic and dichloromethane (DCM) crude extracts of aerial parts of Artemisia abyssinica for in vivo antitrypanosomal activity against Trypanosoma congolense isolate in mice.
Methods
The aerial parts of the plant were extracted by maceration technique using dichloromethane and 80% methanol to obtain the corresponding crude extracts. The plant extracts at doses of 100, 200 and 400 mg/kg body weight were administered intraperitoneally daily for 7 days to mice infected with Trypanosoma congolense. Diminazene aceturate and distilled water were used as positive and as negative controls respectively. The level of parasitaemia, body weight, packed cell volume, differential leukocyte counts and mean survival period were monitored.
Results
The study showed that the DCM extract at 200 and 400 mg/kg, and the hydromethanolic extract at 400 mg/kg reduced parasitaemia (p < 0.05), ameliorated anaemia (p < 0.05), prevented body weight loss (p < 0.05) and resulted in significant increase in neutrophil levels (p < 0.05) and marked decrease in lymphocyte levels (p < 0.05) compared to the negative control.
Conclusions
This study established that aerial parts of A. abyssinica have antitrypanosomal potential and can be considered a potential source of new drugs for the treatment of tropical diseases caused by trypanosomes.
doi:10.1186/1472-6882-14-117
PMCID: PMC4230807  PMID: 24684992
Artemisia abyssinica; Antitrypanosomal activity; Trypanosoma congolense; Mice
19.  Study of antihyperglycaemic activity of medicinal plant extracts in alloxan induced diabetic rats 
Ancient Science of Life  2013;32(4):193-198.
Background:
Diabetes mellitus, for a long time, has been treated with plant derived medicines in Sri Lanka.
Aim:
The aim of this study is to determine the efficacy and dose response of oral antihyperglycaemic activity of eight Sri Lankan medicinal plant extracts, which are used to treat diabetes in traditional medicine in diabetic rats.
Materials and Methods:
Medicinal plants selected for the study on the basis of documented effectiveness and wide use among traditional Ayurveda physicians in the Southern region of Sri Lanka for the treatment of diabetes mellitus. The effect of different doses of aqueous stem bark extracts of Spondias pinnata (Anacardiaceae), Kokoona zeylanica (Celastraceae), Syzygium caryophyllatum (Myrtaceae), Gmelina arborea (Verbenaceae), aerial part extracts of Scoparia dulcis (Scrophulariaceae), Sida alnifolia (Malvaceae), leaf extract of Coccinia grandis (Cucurbitaceae) and root extract of Languas galanga (Zingiberaceae) on oral glucose tolerance test was evaluated. A single dose of 0.25, 0.50, 0.75, 1.00, 1.25, 2.00 g/kg of plant extract was administered orally to alloxan induced (150 mg/kg, ip) diabetic Wistar rats (n = 6). Glibenclamide (0.50 mg/kg) was used as the standard drug. The acute effect was evaluated over a 4 h period using area under the oral glucose tolerance curve.
Statistical Analysis:
The results were evaluated by analysis of variance followed by Dunnett's test.
Results:
The eight plant extracts showed statistically significant dose dependent improvement on glucose tolerance (P < 0.05). The optimum effective dose on glucose tolerance for six extracts was found to be 1.00 g/kg in diabetic rats with the exception of C. grandis: 0.75 g/kg and L. galanga: 1.25 g/kg.
Conclusion:
The aqueous extract of G. arborea, S. pinnata, K. zeylanica, S. caryophyllatum, S. dulcis, S. alnifolia, L. galanga and C. grandis possess potent acute antihyperglycaemic activity in alloxan induced diabetic rats.
doi:10.4103/0257-7941.131970
PMCID: PMC4078468  PMID: 24991066
Antihyperglycaemic activity; blood glucose; diabetes mellitus; oral glucose tolerance test
20.  Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats 
Background
Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats.
Methods
The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats.
Results
Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p < 0.05) decreased the level of TC, TG, and LDL-c, VLDL-c. While it increases the level of HDL-c to a significant (p < 0.05) level. The treatment also resulted in a marked increase in reduced glutathione, glutathione Peroxidase, catalase and superoxide dismutase and diminished level of lipid peroxidation in liver and kidney of STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage.
Conclusion
Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx.
doi:10.1186/1472-6882-14-243
PMCID: PMC4223618  PMID: 25026962
Albizzia Lebbeck Benth; Bark; Diabetes; Streptozotocin; Hypolipidemic; Antioxidant; Histopathology
21.  Evaluation of Antidiabetic Activity and Associated Toxicity of Artemisia afra Aqueous Extract in Wistar Rats 
Artemisia afra Jacq. ex Willd. is a widely used medicinal plant in South Africa for the treatment of diabetes. This study aimed to evaluate the hypoglycemic activity and possible toxicity effect of aqueous leaf extract of the herb administered at different dosages for 15 days in streptozotocin-induced diabetic rats. Administration of the extract at 50, 100, and 200 mg/kg body weight significantly (P < 0.05) increased body weight, decreased blood glucose levels, increased glucose tolerance, and improved imbalance in lipid metabolism in diabetic rats. These are indications of antidiabetic property of A. afra with 200 mg/kg body weight of the extract showing the best hypoglycemic action by comparing favourably well with glibenclamide, a standard hypoglycemic drug. The extract at all dosages tested also restored liver function indices and haematological parameters to normal control levels in the diabetic rats, whereas the kidney function indices were only normalized in the diabetic animals administered with 50 mg/kg body weight of the extract. This investigation clearly showed that in addition to its hypoglycemic activity, A. afra may also protect the liver and blood against impairment due to diabetes. However, some kidney functions may be compromised at high dosages of the extract.
doi:10.1155/2013/929074
PMCID: PMC3687504  PMID: 23861717
22.  Antidiabetic activity of Crateva nurvala stem bark extracts in alloxan-induced diabetic rats 
Objectives:
The aim of this study was to investigate the antidiabetic activity of Crateva nurvala stem bark (family: Capparidaceae) extracts in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of C. nurvala and a known antidiabetic drug glibenclamide (600 μg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in diabetic rats.
Materials and Methods:
The petroleum ether, chloroform, alcohol, and aqueous extracts of C. nurvala stem bark were obtained by simple maceration method and were subjected to standardization by following pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50–5000 mg/kg b. wt.) as per Organization for Economic Co-operation and Development (OECD) guidelines.
Results and Conclusions:
C. nurvala petroleum ether extract (CNPEE) and ethanolic extract (CNEE) showed significant (P< 0.001) antidiabetic activities. In alloxan-induced model, blood glucose level of these extracts on seventh day of study were CNPEE (126.33±13.703 mg/dl) and CNEE (126.66±13.012 mg/dl) when compared with diabetic control (413.50±4.752 mg/dl) and chloroform extract (320.83±13.516 mg/dl). In OGGT model (glucose loaded rats), CNPEE showed a glucose level of 178.83±3.070 mg/dl after 30 min and 131.66±2.486 mg/dl after 90 min, whereas CNEE showed 173.66±4.224 mg/dl after 30 min and 115.50±3.394 mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug.
doi:10.4103/0975-7406.62700
PMCID: PMC3146085  PMID: 21814425
Alloxan; antidiabetic activity; acute toxicity; Crateva nurvala; phytochemical
23.  Assessment of antidiabetic potential of Cinnamomum tamala leaves extract in streptozotocin induced diabetic rats 
Indian Journal of Pharmacology  2011;43(5):582-585.
Objective:
To establish the effect of Cinnamomum tamala leaves extract on diabetes and diabetes induced dyslipidemia in streptozotocin-induced diabetic rats.
Materials and Methods:
Diabetes was induced by a single intravenous injection of streptozotocin (50 mg/kg body weight). Group I and II were kept as control and diabetic control respectively. And group III was further treated with ethanolic leaf extract of C. tamala (200 mg/kg body weight, orally) for a period of 40 days. Oral glucose tolerance test was performed before starting the experiment and blood glucose level was estimated. Statistical analysis was performed using one-way Analysis of Variance (using Statistical Package for the Social Sciences [SPSS] version 10.0) and student's ‘t’- test (Sigma Plot version 8.0). The values of P < 0.05 were considered as statistically significant.
Results:
Treatment of diabetic animals with Cinnamomum tamala extract significantly lowered the blood glucose level, and maintained body weight and lipid-profile parameters towards near normal range.
Conclusion:
The extract exhibited antidiabetic and antidyslipidemic effect. Further, chemical and pharmacological investigations are required to elucidate the exact mechanism of action of this extract and to isolate the active principles responsible for these effects.
doi:10.4103/0253-7613.84977
PMCID: PMC3195132  PMID: 22022005
Cinnamomum tamala; diabetes mellitus; dyslipidemia
24.  Alcoholic leaf extract of Plectranthus amboinicus regulates carbohydrate metabolism in alloxan-induced diabetic rats 
Indian Journal of Pharmacology  2011;43(3):286-290.
Objective:
The present investigation was undertaken to explore the possible mechanisms of Plectranthus amboinicus leaf extract in alloxan-induced diabetic rats.
Materials and Methods:
Control and alloxan-induced diabetic albino rats received different treatments; orally control (vehicle), 200 mg/kg and 400 mg/kg of ethanol extract of Plectranthus amboinicus (PAEE) and 600 μg/kg of glibenclamide (standard) for 15 days. At the end of the experiment, the animals were sacrificed and enzyme activities of carbohydrate metabolism were measured in the liver.
Results:
Diabetic control rats showed a significant elevation (P < 0.001) in fasting blood glucose on successive days of the experiment as compared with their basal values, which was maintained over a period of 2 weeks. Daily oral treatment with PAEE showed a significant reduction (P < 0.001) in the blood glucose levels on successive days of the experiment as compared with their basal values. The most pronounced antihyperglycemic effect was obtained with the dose of 400 mg/kg. PAEE shows a dose-dependent reduction in gluconeogenic enzymes like glucose-6-phosphatase and fructose-1,6-disphosphatase. After 15 days of treatment with PAEE, glycolytic enzymes like phosphoglucoisomerase resulted in a significant increase with a concomitant significant decrease in the activities of aldolase. On the other hand, glucose-6-phosphate dehydrogenase was significantly improved in diabetic rats on administration of PAEE; the 400 mg/kg dose of PAEE elicited a more potent effect compared with the 200 mg/kg dose.
Conclusion:
The results obtained in this study provide evidence of the antidiabetic activity of PAEE, mediated through the regulation of carbohydrate metabolic enzyme activities.
doi:10.4103/0253-7613.81520
PMCID: PMC3113380  PMID: 21713092
Aldolase; alloxan; glucose-6-phosphate dehydrogenase; Plectranthus amboinicus
25.  The Novel Antihyperglycaemic Action of Hunteria Umbellata Seed Fractions Mediated Via Intestinal Glucose Uptake Inhibition 
The present study evaluated the antihyperglycaemic effect and mechanism of action of fractions of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. (HU) in normal and alloxan-induced hyperglycaemic rats. HU was partitioned in chloroform, acetyl acetate and butan-1-ol to give chloroform fraction (HUc), ethyl acetate fraction (HUe), butanol fraction (HUb) and the “residue” (HUm), respectively. 200 mg/kg of each of these fraction dissolved in 5% Tween 20 in distilled water was investigated for its acute oral hypoglycaemic effects in normal rats over 6 hours while its repeated dose antihyperglycaemic effect was evaluated in alloxan-induced hyperglycaemic rats over 5 days. In addition, 50 mg/kg of the crude alkaloid fraction (HUAf) extracted from HU was evaluated for its possible antihyperglycaemic activity in alloxaninduced hyperglycaemic rats using oral glucose tolerance test (OGTT) over 6 hours. Using the solvent system, distilled water-butanol-ammonium hydroxide (2:15:1, v/v/v), HUb was chromatographed and stained with Dragendorff's reagent for confirmatory qualitative analysis for alkaloids. Results showed that oral pre-treatment with 200 mg/kg of HUe, HUb and HUm resulted in a significant (p<0.05, p<0.001) time dependent hypoglycaemic effect, with the butan-1-ol fraction HU causing the most significant (p<0.001) hypoglycaemic effect. In the alloxan-induced hyperglycaemic rats, repeated oral treatment with 200 mg/kg of same HU fractions for 5 days resulted in significant (p<0.05) decreases in the fasting blood glucose concentrations with the most significant (p<0.01) antihyperglycaemic effect also recorded for HUb. Similarly, oral pretreatment with 50 mg/kg of HUAf significantly (p<0.05, p<0.01 and p<0.001) attenuated an increase in the post-absorptive glucose concentration at 1st – 6th h in the alloxan-induced hyperglycaemic OGTT model. In addition, alkaloid was present in most of the separated spots on the TLC plate. In conclusion, results of this study showed that HU contains a relative high amount of alkaloids which could have accounted for the antihyperglycaemic action of HU that was mediated via intestinal glucose uptake inhibition.
PMCID: PMC3744210  PMID: 23983315
Hunteria umbellata aqueous seed extract; Alkaloid fraction; Intestinal glucose uptake inhibition; Normal and alloxan-induced hyperglycaemic rats

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