Assessment of Antidiabetic Potential of Polyherbal Formulations

Introduction: Diabetes provides a major challenge to the present population globally. It is a major threat to global public health that is rapidly reaching epidemic scale. Plant based drugs are gaining importance to treat majority of human aliments including diabetes mellitus due to their less toxic effects. Aims: The present study was designed to assess the antidiabetic potential of polyherbal formulations in streptozotocin induced diabetic rats. Methods:  Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg) in male Wistar rats. Rats with fasting blood glucose levels ≥ 250 mg/dl after seven days of STZ administration were randomized into different groups and were treated with Formulation-1 (F1) and Formulation-2 (F2) in graded doses for 21 days. At the end of the study, blood glucose, lipid profiles were estimated. In addition, enzymatic and non-enzymatic liver antioxidant levels were also estimated. To elucidate the mode of action, we evaluated its effects on oral glucose tolerance test in normal rats and single-dose one day-study and multiple-dose twenty one day- study in diabetic rats. Results:  The effect on the insulin level with the treatment by formulations suggests that the mode of action is a similar to that of Glibenclamide. Oral administration of F1 and F2 for 21 days significantly reduced blood glucose level in STZ induced diabetic rats. Both the formulations exhibited antihyperglycemic effect in glucose loaded rats and STZ induced rats. The blood glucose was significantly increased. Supplementation with F1 and F2 both with (250 and 500 mg/kg) showed reduction in the blood glucose levels and improved glucose tolerance, suggesting that there was an improvement in STZ-induced deleterious effects. Conclusion: This study reveals that F1 and F2 improved STZ-induced hyperglycemia, this effect may be mediated by interacting with multiple targets operating in diabetes mellitus.

Changes in the Oxidative Stress Biomarkers in Liver of Streptozotocin-diabetic Rats Treated with Combretum lanceolatum Flowers Extract.

Aims: The study investigated the in vivo antioxidant activity and the in vitro radical scavenging capacity of the Combretum lanceolatum Pohl (Combretaceae) flowers ethanolic extract (ClEtOH) in streptozotocin-diabetic rats. Place and Duration of Study: Department of Chemistry, Federal University of Mato Grosso, Cuiabá, Brazil; between February 2012 and December 2012. Methodology: Male Wistar rats were divided into four groups: Normal rats treated with water/vehicle (N); diabetic rats treated with water (DC); diabetic rats treated with 250 mg/kg (DT250) or with 500mg/kg (DT500) of ClEtOH. After 21 days of treatment, liver samples were used for the analysis of the oxidative stress biomarkers and activity of antioxidant enzymes. In vitro radical scavenger capacity was investigated by the following methods: DPPH radical scavenging, ABTS radical cation decolorization and crocin bleaching assays. Results: Significant oxidative stress was observed in liver of DC, since the malondialdehyde (MDA, biomarker of lipoperoxidation) levels were increased in comparison with N. Increased activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were also observed in DC, which could represent a compensatory mechanism against oxidative stress. Glutathione (GSH) levels were lower and similar between N and DC. The MDA levels were significantly decreased in liver of rats from DT250 and DT500, reaching levels similar those of N, suggesting that ClEtOH prevented lipoperoxidation. The treatment of diabetic rats with ClEtOH also increased the GSH levels, as well as increased the GSH-Px activity, and did not change the SOD activity. The results of in vitro radical scavenging capacity indicated that ClEtOH is highly active. Conclusion: These findings indicate that ClEtOH has antioxidant properties in liver of diabetic rats, decreasing lipoperoxidation and increasing the endogenous antioxidant responses. Both the antihyperglycemic effect and the capacity to scavenge free radicals may be related to the antioxidant activity of ClEtOH in diabetes.

Anti Diabetic activity of Terminalia superba (Combretaceae) Stem Bark Extract in Streptozotocin Induced Diabetic Rats.

Aims: The present study was designed to evaluate the antidiabetic activity of the methanol stem bark extract of Terminalia superb (T. superba), a traditionally used medicinal plant in Cameroon. Place and Duration of Study: Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, Cameroon and Laboratoire de Pharmacologie et Physiopathologie Expérimentales, Université Montpellier I, France. Between Ferbruary 2011 and September 2011. Methodology: In one set of experiments, repeated doses of T. superba extract (37.5– 300mg/kg, p.o.) were administrated once daily for 21 days to groups of diabetic rats. In another set of experiments, acute effect of the plant extract (37.5–300mg/kg) in diabetic rats was evaluated. Results: Following acute treatment, the plant extract produced a significant reduction in the blood glucose levels in diabetic rats. T. superba (75–300mg/kg) significantly decreased the blood glucose levels in glucose loaded rats. Oral administration of T. superba extract for 21 days resulted in a 31.43% and 21.42% significant reduction in blood glucose levels at the dose of 75mg/kg and 300mg/kg respectively. The plant extract significantly, reduced the plasma urea levels (20%) and induced a significant elevation in plasma insulin in treated rats. The extract did not significantly change elevated plasma cholesterol and triglycerides resulting from diabetic conditions. Conclusion: The antidiabetic effect of the methanol stem bark extract of T. superba seems to be a result of increase in glucose utilization due to stimulatory action on insulin release.

Combretum lanceolatum flowers extract shows antidiabetic activity through activation of AMPK by quercetin

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500 mg/kg of metformin and diabetic treated with 250 or 500 mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500 mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500 mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50 µg/mL of ClEtOH, similarly to the incubation with metformin (50 µg/mL) or quercetin (10 µg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin.

Glycogen depletion / 대한정형외과학회잡지

In this study, the glycogen depletion and repletion of 4 hind limb skeletal muscles which are composed of different type of muscle fibers were investigated in the streptozotocin induced diabetic rats. At sixth day after intraperitoneal injection of streptozotocin (65mg/kg, BW), the plasma insulin level was decreased to 28.2 ±4.16u U/ml comparing with the level of 49.3 ±9.41 in control rats, And it showed approximatly 300% increment of the level of blood glucose concentration in the sedentary diabetic rats. The soleus (slow oxidative), rad gastrocnemius (fast oxydtive glycolytic), extensor digitorum longus (fast oxidative glycolytic and fast glycolytic mixed), and white gastrocnemius (fast gltycolytic) were subjected in this study. The decreased amount of glycogen in the muscles by 3 minutes treadmill running in disbetic rats was larger than that of control rats. The largest amount of depletion was observed in the soleus in diabetic rats. The repleted amount of muscle glycogen was measured at 2 hours after glucose ingestion (25% glucose sol., 2ml/10gm BW). In the control rats, the highest amount of glycogen was repleted in the soleus, but lowest in white gastrocnemius. The repleted amount of glycogen in soleus, red gastrocnemius, and extensor digitorum longus was lower in the muscles of diabetic rats than in control rats, but no difference was observed in white gastroenemius muscles. These data suggest that glycogen synthetic activities of all of muscles except the muscles which are composed of fast glycolytic fiber, were stimulated by insulin.