Antihyperglycemic effect of the traditional Chinese scutellaria–coptis herb couple and its main components in streptozotocin-induced diabetic rats

Ethnopharmacological relevance

Scutellaria–coptis herb couple (SC) is the main herb couple in many traditional Chinese compound formulas used for the treatment of diabetes mellitus, which has been used to treat diabetes mellitus for thousands of years in China. In this study we provide experimental evidence for the clinical use of SC in the treatment of diabetes mellitus.

Aim of the study

To confirm the anti-diabetic effect of SC extract and its main components, and to explore its mechanism from the effect on intestinal disaccharidases by in vivo and in vitro experiment.

Materials and methods

SC extract was prepared and the main components (namely berberine and baicalin) contained in the extract were assayed with high performance liquid chromatography (HPLC). And diabetic model rats were induced by intraperitoneal injection of streptozotocin (STZ). After grouped randomly, diabetic rats were administered SC extract, berberine, baicalin, berberine+baicalin, acarbose and vehicle for 33 d, respectively. Body weight, food intake, urine volume, urine sugars, fasting plasma glucose and fasting plasma insulin were monitored to evaluate the antidiabetic effects on diabetic rats. Intestinal mucosa homogenate was prepared and the activities of intestinal disaccharidases were assayed. Moreover, oral sucrose tolerance test (OSTT) was performed and the inhibitory effects of SC extract and its main components (berberine and baicalin) on the maltase and sucrase in vitro was evaluated.

Results

After the treatment of SC extract and its main components, the body weight and the fasting plasma insulin level were found to be increased while food intake, urine volume, urine sugars and fasting plasma were decreased. OSTT showed that SC extract and its main components could lower the postprandial plasma glucose level of diabetic rats. Furthermore, SC extract and its main components could inhibit the activities of intestinal disaccharidases in diabetic rats, whereas only SC extract and berberine could inhibit the activity of maltase in vitro.

Conclusions

According to our present findings, scutellaria–coptis herb couple (SC) possessed potent anti-hyperglycemic effect on STZ-induced diabetic rats. And SC extract and its main components exerted anti-hyperglycemic effect partly via inhibiting the increased activities of intestinal disaccharidases and elevating the level of plasma insulin in diabetic rats induced by STZ.     

Antidiabetic activity of Paspalum scrobiculatum Linn. in alloxan induced diabetic rats

Ethnopharmacological relevance

Paspalum scrobiculatum Linn. (Poaceae) is traditionally used to treat diabetes mellitus. The grains of Paspalum scrobiculatum are having potential in the development of drug for diabetes due to their antidiabetic activity.

Aim of the study

To evaluate the antidiabetic activity of aqueous and ethanolic extracts of grains of Paspalum scrobiculatum Linn. (Poaceae) in alloxan induced diabetic rats.

Materials and methods

Aqueous and ethanolic extracts (250 and 500 mg/kg body weight), were administered orally to male Wistar albino rats. Alloxan monohydrate was used to induce diabetes mellitus. Total phenolic content was estimated in the extracts. The parameters studied included oral glucose tolerance test, fasting blood glucose, serum insulin and glycated haemoglobin levels, liver glycogen content, serum lipid profile, and changes in body weights.

Results

In oral glucose tolerance test, reduction of fasting blood glucose levels took place from 60 min of extract administration. The extracts produced a dose-dependent fall in fasting blood glucose (FBG). After 15 days of treatment with extracts the maximum reduction in FBG (35.14%) was observed in diabetic rats treated with ethanolic extract 500 mg/kg dose. A significant increase in serum insulin level was observed in the treated rats. Serum lipid levels were reversed towards near normal and a control in the loss of body weight was observed in treated rats as compared to diabetic control. The extract treatment also showed a significant increase in the liver glycogen and a significant decrease in glycated haemoglobin levels. The results demonstrate that Paspalum scrobiculatum possesses significant antidiabetic activity in diabetic rats.

Conclusion

The results suggest that Paspalum scrobiculatum has antidiabetic activity, thereby justifying its traditional claim and augmenting it into the present day systems of medicine.     

In vitro and in vivo anti-diabetic activity of Swertia kouitchensis extract

Ethnopharmacological relevance

Swertia kouitchensis has long been used as a folk medicine to treat hepatitis and diabetes in central-western China. Therefore, this study was aimed to evaluate the anti-diabetic activity of the plant ethanol extract.

Materials and methods

Firstly, the extract was tested for its inhibitory activity on α-amylase and α-glucosidase in vitro. Following that, insulin secretion test in NIT-1cell was performed. Then, oral sucrose or starch tolerance test of the extract were carried out in normal mice. After that, acute effect of the extract was executed in normal and streptozotocin-induced (60 mg/kg) diabetic mice. Eventually, long term effect of the extract was performed in diabetic mice for 4 weeks. Oral glucose tolerance test and biochemical parameters were estimated at the end of the study.

Results

Swertia kouitchensis extract could remarkably inhibit the activity of α-amylase and α-glucosidase and stimulate insulin secretion in vitro. And also the extract displayed anti-hyperglycemic activity, improved antioxidant capacity, ameliorated the hyperlipidemia and carbohydrate metabolism in diabetic mice.

Conclusions

Swertia kouitchensis exhibits considerable anti-diabetic activity and metabolic alterations in diabetic mice. These results provide a rationale for the use of Swertia kouitchensis to treat diabetes mellitus.     

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.     

Two new compounds from the aerial parts of Bergenia himalaica Boriss and their anti-hyperglycemic effect in streptozotocin-nicotinamide induced diabetic rats

Ethnopharmacological relevance

Bergenia himalaica Boriss is mainly distributed in the temperate Himalayas between altitudes of 900 and 3000 m ranging from the southeastern regions in central Asia and northern regions in South Asia. The plant has a long history of its use in traditional medicine for the treatment of various diseases such as diabetes, urinary complaints, kidney stones, hemorrhagic diseases and epilepsy. The aim of this study is to isolate pure compounds from Bergenia himalaica Boriss, elucidate their structures and determine their blood glucose lowering activity to obtain additional scientific evidence for its usage in traditional medicine for the management of diabetes.

Materials and methods

The crude methanolic extract from the aerial parts of Bergenia himalaica Boriss was separated into EtOAc and water sub-extracts and the EtOAc sub-extract was further divided into petroleum ether soluble and insoluble fractions. The pet-ether insoluble fraction was subjected to fractionation through column chromatography followed by prep. TLC. The blood glucose lowering activity of the 2 new compounds was evaluated in streptozotocin–nicotinamide induced diabetic rats. Additionally, glucose-stimulated insulin secretion was measured on isolated mice islets.

Results

Two new compounds bergenicin and bergelin were isolated and their structures determined on the basis of spectral analysis. Significant decrease of blood glucose was observed at 1-h (1.0 mg/kg) and 2-h (0.5 mg/kg), after bergenicin administration to the diabetic rats and at 2-h (1.0 mg/kg) and 3-h (0.5 mg/kg), after bergelin administration. Bergenicin, but not bergelin, enhanced glucose-stimulated insulin secretion in isolated pancreatic islets.

Conclusions

In the present studies two new compounds, bergenicin and bergelin were isolated from Bergenia himalaica Boriss and their structures were elucidated. Both the compounds showed anti-hyperglycemic effects in streptozotocin–nicotinamide induced diabetic rats. Bergenicin showed insulinotropic effect; suggesting that the anti-hyperglycemic effect is mostly due to enhancement of insulin secretion from pancreatic β-cells.     

Anti-hyperglycemic effect,inhibition of inflammatory cytokines expression,and histopathology profile in streptozotocin-induced diabetic rats treated with Arracacia tolucensis aerial-parts extracts

Ethopharmacological relevance

Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats.

Materials and methods

DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1 mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out.

Results

Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited.

Conclusion

These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use.     

Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats

Ethnopharmacological relevance

In traditional Indian medicine, all parts of Emblica officinalis Gaertn plant including the fruit, seed, leaves, root, bark and flowers are used in various herbal preparations for the treatment of diabetes mellitus, chronic diarrhea, anti-inflammatory and antipyretic.

Aim of the study

To evaluate the hypoglycemic and antioxidants effects of the hydro-methanolic (20:80) extract of leaves of Emblica officinalis Gaertn. (HMELEO) in streptozotocin induced diabetic rats.

Material and methods

The hypoglycemic effect was measured by blood glucose and plasma insulin level. The oxidative stress was measured in liver and kidney by level of antioxidant markers i.e. lipid peroxidation (LPO), superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxidase (GPx) and catalase (CAT), and the biochemical parameters, i.e. blood serum levels of creatinine, urea, serum glutamic pyruvic transaminases (SGPT), serum glutamic oxaloacetic transaminases (SGOT), alkaline phosphatase (ALP), total cholesterol and triglyceride levels were the salient features observed in diabetic control and treated rats.

Results

Oral administration of the HMELEO at a concentration of 100, 200, 300 and 400 mg/kg b.w. daily for 45 days showed a significant (P<0.05) decrease in fasting blood glucose and increase insulin level as compared with the diabetic rats. Also it significantly (P<0.05) reduced all biochemical parameters (serum creatinine, serum urea, SGOT, SGPT and lipid profile). The treatment also resulted in a significant (P<0.05) increase in reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, and decrease LPO level in the liver and kidney of diabetic rats.

Conclusion

The results clearly suggest that the hydro methanolic extract of leaves of Emblica officials Gaertn. treated group may effectively normalize the impaired antioxidant status in streptozotocin induced diabetes at dose dependent manner than the glibenclamide-treated groups. The extract exerted rapid protective effects against lipid peroxidation by scavenging of free radicals and reducing the risk of diabetic complications.     

Effect of Moringa oleifera Lam. leaves aqueous extract therapy on hyperglycemic rats

Ethnopharmacological relevance

In Indian traditional system of medicine, Moringa oleifera Lam. Syn. Moringa pterygosperma Gaerth (Moringaceae) is commonly used as healing herb to treat diabetes.

Aim of the study

The purpose of the present study was to assess the effect of M. oleifera leaves aqueous extract therapy on glycemic control, haemoglobin, total protein, urine sugar, urine protein and body weight.

Materials and methods

Variable doses of 100, 200 and 300 mg kg⁻¹ of aqueous extract were administered orally by gavage for evaluating their hypoglycemic and antidiabetic effects on fasting blood glucose (FBG), oral glucose tolerance test (OGTT) and post prandial glucose (PPG) of normal and streptozotocin (STZ) induced sub, mild and severely diabetic rats.

Results

The dose of 200 mg kg⁻¹ decreases blood glucose level (BGL) of normal animals by 26.7 and 29.9% during FBG and OGTT studies respectively. In sub and mild diabetic animals the same dose produced a maximum fall of 31.1 and 32.8% respectively, during OGTT. In case of severely diabetic animals FBG and PPG levels were reduced by 69.2 and 51.2% whereas, total protein, body weight and haemoglobin were increased by 11.3, 10.5 and 10.9% respectively after 21 days of treatment. Significant reduction was found in urine sugar and urine protein levels from +4 and +2 to nil and trace, respectively.

Conclusion

The study validates scientifically the widely claimed use of M. oleifera as an ethnomedicine to treat diabetes mellitus.     

Hypoglycemic and antihyperglycemic effect of Begonia malabarica Lam. in normal and streptozotocin induced diabetic rats

Aim of the study

The stem of Begonia malabarica was used traditionally by the Malasar tribe to treat diabetes. To validate the hypoglycemic and antihyperglycemic effects of the hexane, ethylacetate and methanol extracts obtained from an ethnomedicinal plant, Begonia malabarica.

Materials and methods

The doses for the study were fixed based on Irwin test. The hypoglycemic effect of hexane, ethylacetate and methanol extracts of Begonia malabarica stems were studied in normal animals. The antihyperglycemic effect of the methanol extract was studied in streptozotocin induced diabetic rats.

Results

In normal rats the treatment with the methanol extract of Begonia malabarica had shown a highly significant reduction (16.54 and 34.47%) in plasma glucose levels from the 0 h values at the dose of 100 and 200 mg/kg respectively. In streptozotocin induced diabetic rats the body weight of the Begonia malabarica methanol extract treated animals had shown a significant increase (13.38% at 200 mg/kg) after 4 weeks treatment. The plasma glucose levels were reduced significantly by 46.57 and 50.20% after 4 weeks treatment at 100 and 200 mg/kg respectively. Likewise the absolute kidney weight was also reduced in a significant manner. After 25 days treatment the Begonia malabarica methanol extract treated animals had shown low fasting plasma glucose levels (54.29, 61.34% in 100 and 200 mg/kg) and reduced postprandial plasma glucose levels (54.23, 65.96% in 100 and 200 mg/kg) when compared with diabetic control values. Serum insulin levels and liver glycogen levels were increased to 40.04 and 42.18% in 200 mg/kg Begonia malabarica methanol extract treated animals respectively. The treatment with Begonia malabarica methanol extract did not change the triglycerides and total cholesterol levels. The urea and creatinine levels were also reduced significantly by this treatment. The reduction in SGPT levels indicated the absence of toxicity of Begonia malabarica extract at this dose level.

Conclusion

This study supports the use of Begonia malabarica by the Malasar tribe for the treatment of diabetes. Fractionation of this extract may yield novel prototypes to manage diabetes mellitus.     

Antidiabetic effects of Swertia macrosperma extracts in diabetic rats

Ethnopharmacological relevance

Swertia macrosperma is a traditional folk medicine used for its anti-hepatitis, antipyretic and antidotal effects as “Dida” or “Zangyinchen” in Tibet, Yunnan and Guizhou province for a long time, and it has been reported for its anti-diabetic effects in a Chinese patent. Swertia macrosperma was reported rich in xanthones, iridoids, seco-iridoids and their glycosides, several of which had been documented as potential antidiabetic agents. The objective of this study was to investigate the antidiabetic effect of Swertia macrosperma in diabetic rats.

Materials and methods

This study was designed firstly to evaluate the effect of Swertia macrosperma on glucose consumption in HepG2 cells. Based on the result in HepG2 cells, the antidiabetic effect of ethanol extract (EE) and n-butanol extract (BE) were investigated in diabetic rats induced by high fat fed and streptozotocin. The effects of EE and BE on fasting blood glucose, oral glucose tolerance test, serum insulin, glycosylated hemoglobin, serum lipid level, serum antioxidant parameters, glucokinase, glucose-6-phosphatase activities and glycogen content in liver tissue were measured, histology examination of pancreatic tissue was also carried out.

Results

After 4 weeks treatment with EE and BE, apparently decreased fasting blood glucose concentrations were observed in these treated groups, compared with the diabetic control groups. Additionally, improvement in serum antioxidant parameters and lipid profile were evidenced clearly. Moreover, EE and BE had effects of protecting the pancreatic β-cells and stimulating insulin secretion from the remaining pancreatic β-cells, evidenced by pancreatic histology examination. Increased glucokinase activity and decreased glucose-6-phosphatase activity were observed in liver.

Conclusion

The results of in vivo and in vitro experiment suggested that EE and BE of Swertia macrosperma had excellent effects on controlling the hyperglycemia and hyperlipidemia in diabetic rats.     

Antioxidant and anti-inflammatory effects of Urtica pilulifera extracts in type2 diabetic rats

Ethnopharmacological relevance

"Urtica pilulifera has been traditionally used in Egyptian system as an herbal remedy to be a diuretic, antiasthmatic, anti-inflammatory, hypoglycemic, hemostatic, antidandruff and astringent"

Aim of the study

To evaluate the potential effects of ethyl acetate (EA), chloroform (CHLOR) and hexane (HEXA) extracts of Urtica piluliferaas oral anti-diabetic agents as well as to evaluate their possible anti-oxidant and anti-inflammatory effects in type2 diabetic rat model.

Material and methods

Type2 diabetes was induced by a high fat diet and low dose streptozotocin (STZ). Diabetic adult male albino rats were allocated into groups and treated according to the following schedule; Pioglitazone HCL (PIO), EA, CHLOR and HEXA extracts of Urtica pilulifera at two doses of 250 and 500 mg/kg were used. In addition, a normal control group and a diabetic control one were used for comparison. Blood glucose, insulin resistance, antioxidant enzymes, 8-hydroxy-2-deoxyguanosine (8-OHdG) as well as C-reactive protein and tumor necrosis factor-α levels were evaluated.

Results

EA and CHLOR extracts of Urtica pilulifera exhibited a significant hypoglycemia associated with antioxidant and anti-inflammatory effects in diabetic rats; however, HEXA extract showed no beneficial effect. These activities are responsible, at least partly, for improvements that have been seen in hyperglycemia and insulin resistance of diabetic rats.

Conclusion

Our results encourage the traditional use of Urtica pilulifera extract as an antioxidant and anti-inflammatory agent as an additional therapy of diabetes.     

Antidiabetic effects of Artemisia sphaerocephala Krasch. gum,a novel food additive in China,on streptozotocin-induced type 2 diabetic rats

Aim of the study

Since ancient times, practicians of traditional Chinese medicine have discovered that Artemisia sphaerocephala Krasch. (Asteraceae) seed powder was useful for the treatment of diabetes. Artemisia sphaerocephala Krasch. gum (ASK gum), which is extracted from seed powder of the plant, is a novel food additive favored by the food industry in China. The objective of this study was to determine the antidiabetic function of ASK gum on type 2 diabetes.

Materials and methods

Type 2 diabetic rat model was induced with high fat diet and low dose of streptozotocin (STZ). The effects of ASK gum on hyperglycemia, hyperlipemia, insulin resistance, and liver fat accumulation in type 2 diabetic rats were evaluated. The results were compared to those of normal rats and diabetic rats treated with metformin.

Results

The addition of ASK gum to the rats’ food supply significantly lowered fasting blood glucose, glycated serum protein, serum cholesterol, and serum triglyceride in type 2 diabetic rats, and significantly elevated liver glucokinase, liver glycogen, and serum high density protein cholesterol in the diabetic rats. ASK gum significantly reduced insulin resistance and liver fat accumulation of type 2 diabetes.

Conclusion

: Artemisia sphaerocephala Krasch. gum can alleviate hyperglycemia, hyperlipemia and insulin resistance of type 2 diabetes.     

Identification of trans-tiliroside as active principle with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis

Aim of the study

The present study was carried out to isolate and identify trans-tiliroside as principal compound with anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects from Potentilla chinesis.

Materials and methods

A bioactive compound, trans-tiliroside was isolated from the ethanol extract of Potentilla chinesis and its administration dose was optimized and patented. The normal, alloxan-induced diabetic mice and streptozotocin-induced diabetic rats were used to evaluate the anti-hyperglycemic, anti-hyperlipidemic and antioxidant effects of trans-tiliroside from Potentilla chinesis. Biochemical parameters were assayed in blood samples of different groups of alloxan-induced diabetic mice and streptozotocin-induced diabetic rats.

Results

The level of fasting serum glucose levels, triglycerides (TG) and total cholesterol (TC) in alloxan-induced diabetic mice were significantly decrease after daily oral administration of trans-tiliroside in normal and diabetic mice at doses of 0.4, 0.8 and 1.6 mg/kg/day, for 15 days. Blood glucose level was significant decrease in STZ induced diabetic rats by trans-tiliroside (1.2 and 0.3 mg/kg body weight for 10 weeks). The content of TC, low density lipoprotein (LDL-C) and TG levels were decreased and high density lipoprotein (HDL-C) content was increased, so lipid metabolism was improved. Moreover, trans-tiliroside revealed antioxidant activity as shown by increased activities of superoxide dismutase (SOD), decreased level of malondialdehyde (MDA) in diabetic rats. Histological morphology examination showed that the trans-tiliroside restored the damage of pancreas tissues in rats with diabetes mellitus.

Conclusion

Trans-tiliroside, a constituent from Potentilla chinesis, revealed significant anti-hyperglycemic, anti-hyperlipidemic and antioxidant activities.     

Anti-hyperglycemic activity of the leaves of Tetracera scandens Linn. Merr. (Dilleniaceae) in alloxan induced diabetic rats

Aim of the study

The present study was aimed to investigate the anti-diabetic potential of the leaves of Tetracera scandens Linn. Merr. (Dilleniaceae) in vivo with regard to prove its efficacy by local herbalists in the treatment of diabetes frailties.

Materials and methods

Crude aqueous (AQ) and methanol (MEOH) extracts of the leaves of T. scandens L. were administered to both normal and alloxan induced diabetic male albino rats (Wistar strain). The blood glucose levels were measured at 0, 2, 4, 6 and 8 h after oral administration of AQ and MEOH extracts.

Results

Significant reduction in glucose was observed in fasting blood glucose levels in the treated diabetic rats without causing any hypoglycemic effect compared to normal rats. Both polar extracts of the leaves of T. scandens L. exhibited significant anti-hyperglycemic activity at different doses and intervals. The highest anti-hyperglycemic effect (62.5%) was observed by the AQ extract at 0.25 g/kg body weight (b.w.) and MEOH extract (36.5%) at 0.5 g/kg b.w. after 8 h. The significant anti-hyperglycemic activity was found to be comparable with a known oral synthetic hypoglycemic drug, glibenclamide 0.25 mg/kg b.w.

Conclusion

This study provides scientific evidence that the leaves of T. scandens L. have anti-diabetic efficacy and justifies its utility by local herbalists. However, more experiments at the clinical levels are required to confirm the utility of this plant by traditional practitioners in the management of diabetes mellitus.     

Antidiabetic effect of Ficus religiosa extract in streptozotocin-induced diabetic rats

Aims of study

In Indian traditional system of medicine, Ficus religiosa (Family Moraceae) is prescribed for the treatment of diabetes mellitus. In the present study, the antidiabetic effect of aqueous extract of Ficus religiosa bark (FRAE) was investigated in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.

Materials and methods

Oral administration of FRAE at the doses of 25, 50 and 100 mg/kg was studied in normal, glucose-loaded and STZ-diabetic rats.

Results

The three doses caused significant reduction in blood glucose levels in all the models. The effect was more pronounced in 50 and 100 mg/kg than 25 mg/kg. FRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle of STZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. FRAE also showed significant antilipidperoxidative effect in the pancreas of STZ-induced diabetic rats. The antidiabetic effect of Ficus religiosa was compared with glibenclamide, a well-known hypoglycemic drug.

Conclusion

The results indicate that aqueous extract of Ficus religiosa bark possesses significant antidiabetic activity.     

Natural product vindoline stimulates insulin secretion and efficiently ameliorates glucose homeostasis in diabetic murine models

Ethnopharmacological relevance

Catharanthus roseus (L). Don (Catharanthus roseus) is a traditional anti-diabetic herb widely used in many countries, and the alkaloids of Catharanthus roseus are considered to possess hypoglycemic ability.

Aim of the study

To systematically investigate the potential anti-diabetic effects and the underlying anti-diabetic mechanisms of vindoline, one of the alkaloids in Catharanthus roseus.

Materials and methods

The regulation of vindoline against the glucose-stimulated insulin secretion (GSIS) was examined in insulinoma MIN6 cells and primary pancreatic islets. Insulin concentration was detected by Elisa assay. Diabetic models of db/db mice and type 2 diabetic rats induced by high-fat diet combining with streptozotocin (STZ/HFD-induced type 2 diabetic rats) were used to evaluate the anti-diabetic effect of vindoline in vivo. Daily oral treatment with vindoline (20 mg/kg) to diabetic mice/rats for 4 weeks, body weight and blood glucose were determined every week, oral glucose tolerance test (OGTT) was performed after 4 weeks.

Results

Vindoline enhanced GSIS in both glucose- and dose-dependent manners (EC₅₀=50 μM). It was determined that vindoline acted as a Kv2.1 inhibitor able to reduce the voltage-dependent outward potassium currents finally enhancing insulin secretion. It protected β-cells from the cytokines-induced apoptosis following its inhibitory role in Kv2.1. Moreover, vindoline (20 mg/kg) treatment significantly improved glucose homeostasis in db/db mice and STZ/HFD-induced type 2 diabetic rats, as reflected by its functions in increasing plasma insulin concentration, protecting the pancreatic β-cells from damage, decreasing fasting blood glucose and glycated hemoglobin (HbA_1c), improving OGTT and reducing plasma triglyceride (TG).

Conclusion

Our findings suggested that vindoline might contribute to the anti-diabetic effects of Catharanthus roseus, and this natural product may find its more applications in the improvement of β-cell dysfunction and further the potential treatment of type 2 diabetes.     

Comparative pharmacokinetic investigation on baicalin and wogonoside in type 2 diabetic and normal rats after oral administration of traditional Chinese medicine Huanglian Jiedu decoction

Ethnopharmacological relevance

Huanglian Jiedu decoction (HLJDD) is used traditionally in China for the treatment of diabetes mellitus in clinical practice, which has been proved to be effective. The purpose of this study was to investigate the pharmacokinetic characteristics (especially the area under the curve, AUC) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract and to explore its possible mechanism.

Materials and methods

HLJDD extract and Radix scutellariae extract were prepared and the contents of baicalin and wogonoside contained in two extracts were assayed with high performance liquid chromatography (HPLC). Type 2 diabetic rats were induced by high fat diet and intraperitoneal injection of streptozotocin. Pharmacokinetics of baicalin and wogonoside in type 2 diabetic and normal control rats after oral administration of HLJDD extract or Radix scutellariae extract were investigated. Pharmacokinetics of baicalin in type 2 diabetic and normal rats after oral administration of pure baicalin was also investigated.

Results

The pharmacokinetic parameters (especially AUCs) of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract were remarkably different from those in normal rats. And the alterations of the AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of Radix scutellariae extract were similar to those after oral administration of HLJDD extract. Moreover, the increase of the AUC of baicalin in type 2 diabetic rats after oral administration of pure baicalin was similar to that after oral administration of HLJDD extract or Radix scutellariae extract.

Conclusion

The pharmacokinetic behaviors of baicalin and wogonoside (especially the systemic exposure [AUCs] of baicalin and wogonoside) were significantly altered in type 2 diabetic rats after orally administrated HLJDD extract. And the increased AUCs of baicalin and wogonoside in type 2 diabetic rats after oral administration of HLJDD extract resulted from neither the effects of other herbs contained in HLJDD nor the effects of other components contained in Radix scutellariae. It might result from the effects of the pathological status of type 2 diabetes mellitus.     

Extract isolated from Angelica hirsutiflora with insulin secretagogue activity

Ethnopharmacological relevance

Angelica genus (Umbelliferae) has traditionally been used as the medicine and health food considered alleviating several disorders including diabetes mellitus. Angelica hirsutiflora Liu Chao & Chuang is an endemic species and a folk medicine in Taiwan.

Aim of the study

The scientific evidence of anti-diabetic effect for Angelica hirsutiflora remains unknown. The methanolic extracts isolated from Angelica hirsutiflora were studied for its insulin secretagogue and hypoglycemic activities.

Materials and methods

The in vitro effects and possible mechanisms of Angelica hirsutiflora extract on the insulin secretion in isolated mouse and human islets and pancreatic β-cell line HIT-T15 were determined; and tested the regulation of blood glucose in fasted mice and high-fat diet-induced diabetic mice.

Results

Angelica hirsutiflora extract potently stimulated the release of insulin from cultured HIT-T15 cells and isolated mouse and human islets. The intracellular calcium levels were also increased in HIT-T15 cells and isolated human islets treated with Angelica hirsutiflora extract. Angelica hirsutiflora extract was capable of enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2 protein in HIT-T15 cells. Specific ERK inhibitor PD98059 inhibited the increase of insulin secretion by Angelica hirsutiflora extract in HIT-T15 cells and isolated mouse islets. When Angelica hirsutiflora extract was administered to the fasted mice, it decreased the rise in blood glucose level after starch loading. The plasma insulin level was also increased by Angelica hirsutiflora extract treatment. In high-fat diet-induced diabetic mice, Angelica hirsutiflora extract markedly improved the oral glucose intolerance as compared with the vehicle control.

Conclusions

These findings support that Angelica hirsutiflora extract may be useful in the control of hyperglycemia in non-insulin-dependent diabetes mellitus by acting as an insulin secretagogue.     

Antidiabetic and antioxidant activities of Toddalia asiatica (L.) Lam. leaves in Streptozotocin induced diabetic rats

Ethnopharmacological relevance

The leaves of Toddalia asiatica (L.) Lam. have been utilized traditionally for the cure of diabetes.

Aim of the study

The present study was aimed to assess the antidiabetic and antioxidant effects of T. asiatica leaves in Streptozotocin (STZ) induced diabetic rats.

Materials and methods

The phytochemical screening, total phenolic content, HPLC analysis, acute toxicity study and oral glucose tolerance test were carried out. Glucose lowering effect of the hexane, ethyl acetate and methanol extracts of T. asiatica leaves was studied in STZ-induced diabetic rats. The antidiabetic and antioxidant activities were studied for the ethyl acetate extract. The effects of extracts on blood glucose, body weight, plasma insulin, total protein, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and activities of SOD, CAT and GPx were analyzed.

Results

T. asiatica leaves ethyl acetate extract (TALEe) showed highly significant blood glucose lowering effect. Phytochemical evaluation of TALEe showed the presence of alkaloids, terpenoids, cumarins, flavonoids and phenolic compounds. The total phenolic content of TALEe was 126 mg of gallic acid equivalents/g extract. HPLC analysis revealed the presence of flindersine and ulopterol. Acute toxicity study of TALEe revealed no death or toxicity. The oral glucose tolerance test showed lowered area under curve (AUC_glucose) values in TALEe treated rats. After treatment with TALEe (250 and 500 mg/kg) for 28 days there was a significant decrease in blood glucose, plasma enzymes (SGOT, SGPT and ALP) and significant increase in body weight, total protein, serum insulin and liver glycogen levels in treated diabetic rats. The activities of antioxidant enzymes SOD, CAT and GPx were reversed to near normal in treated diabetic rats. Histopathology of pancreas in TALEe treated groups showed regeneration of β-cells.

Conclusion

The results of the experiments showed that TALEe exerted significant antidiabetic and antioxidant effects in STZ-induced diabetic rats justifying its traditional use.     

Antidiabetic activity of Ficus amplissima Smith. bark extract in streptozotocin induced diabetic rats

Ethnopharmacological relevance

Ficus amplissima commonly known as kal-itchchi have a long history of use in Ayurveda, Siddha and Unani herbal preparations in Indian traditional system of medicine. It has been used in folklore medicine for the treatment of diabetes.

Aim

The aim of the present study was to evaluate the effect of methanolic extract of the bark of Ficus amplissima (FAB) in streptozotocin-induced diabetic rats.

Materials and methods

Oral administration of FAB bark at the doses of 50 mg/kg, 100 mg/kg and 150 mg/kg was studied in normal, glucose-loaded and STZ—induced diabetic rats.

Results

The three doses caused significant reduction in blood glucose levels in all the models. The effect was more pronounced in 50 mg/kg and 100 mg/kg than 150 mg/kg. FAB also showed significant increase in serum insulin and body weight. The glycogen content in liver, skeletal muscle, total protein contents were markedly increased and marker enzymes of hepatic function of STZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. FAB also showed significant anti-lipid peroxidative effect in the pancreas of STZ-induced diabetic rats. The anti-diabetic effect of FAB was compared with glibenclamide, a well known hypoglycemic drug. Histological analysis showed the regenerative effect of FAB on the β-cells of diabetic rats.

Conclusion

Results of this experimental study indicated that FAB possessed anti-diabetic and antioxidant activities. Hence it could be used as a natural source of antidiabetic (Type-I) and antioxidant drug.