Insulinotropic activity of Tinospora crispa extract: effect on ß-cell Ca2+ handling

The mechanism of insulinotropic action of Tinospora crispa was investigated in vitro using an insulin-secreting clonal ß-cell line, HIT-T15. The aqueous extract sensitizes the ß-cell to extracellular Ca²⁺ and promotes intracellular Ca²⁺ accumulation which in turn causes increased insulin release. The increase in cytosolic Ca²⁺ concentration is due to stimulation of Ca²⁺ uptake from the extracellular medium and inhibition of Ca²⁺ efflux from the cytosol. That the mechanism of insulinotropic action of T. crispa is physiological suggests that the insulin secretagogue/s present in the extract could indeed be a potential source of a specific oral hypoglycaemic agent for the treatment of non-insulin-dependent diabetes mellitus. © 1998 John Wiley & Sons, Ltd.     

Induction of insulin secretion by an aqueous extract of Tabernanhte iboga Baill. (Apocynaceae) in rat pancreatic islets of Langerhans

The effect of an aqueous extract of Tabernanthe iboga (TBEt) was studied in the rat islets insulin secretion based on its use in traditional medicine for the treatment of diabetes. Rats islets were isolated by collagenase digestion. In insulin release experiments, the insulin content was determined by Enzyme-Link Immunosorbent Assay (ELISA). For experiments on ⁴⁵Ca²⁺ Uptake, the radioactive content was determined using a liquid scintillation analyzer. The extract (10⁻³ μg/ml-100 μg/ml) did not exert a significant increase of insulin secretion (p > 0.05) in the presence of 2.8 mM of glucose (a none stimulatory concentration). Whereas, in the presence of 11.1 mM of glucose (stimulatory concentration), TBEt augmented glucose-stimulated insulin secretion in a dose-dependent manner. Interestingly, the secretory effect of the extract was glucose-dependent (5.6-16.7 mM). Furthermore, the insulinotropic effect of TBEt (1 μg/ml) was significantly potentiated (p < 0.001) in K⁺-depolarised media as well as in the presence of 2.8 mM and 16.8 mM of glucose concentrations. In contrast, in the same conditions, TBEt failed to stimulate the high K⁺ medium-induced insulin release. The extract significantly amplified (p < 0.001 and p < 0.05) the insulin secretion induced by either IBMX or tolbutamide. Diazoxide, cobalt or calcium removal inhibited the insulinotropic effect of the extract. TBEt increased glucose-induced ⁴⁵Ca²⁺ uptake in rat islets. Overall, our findings suggest that Tabernanthe iboga contains water soluble insulinotropic compounds. The insulin secretion of TBEt's active principles might involve the closure of K⁺-ATP and the intensification of calcium influx through voltage-sensitive Ca²⁺ channels.     

Antihyperglycemic effect of a natural chicoric acid extract of chicory (Cichorium intybus L.): A comparative in vitro study with the effects of caffeic and ferulic acids

Ethnopharmacological relevance

In Eurasia folk medicine, roots of chicory (Cichorium intybus L.) have been reported to exert antidiabetic benefits. In vitro, a natural chicoric acid extract (NCRAE) from Cichorium intybus root has been shown to increase insulin secretion by pancreatic β-cells and glucose uptake by muscle cells.

Materials and methods

In vitro experiments were designed to compare the effects of two hydroxycinnamic acids, caffeic and ferulic acids, to those obtained with NCRAE (50 and 100 µg.mL⁻¹) on the three major tissues implicated in glycemic regulation (pancreas, muscle and liver). In vivo experiments were performed in Wistar rats submitted to a daily intraperitoneal injection of NCRAE (3, 15 or 30 mg kg⁻¹) for 4 days. On the fourth day, an intraperitoneal glucose tolerance test (IPGTT; 1 g kg⁻¹) was carried out.

Results

Our results show that the three compounds we used are able each to induce an original response. Caffeic acid mainly promotes a decrease in hepatic glycogenolysis. Ferulic acid elicits a clear increase of insulin release and a reduction of hepatic glycogenolysis. However, this compound induces an inhibition of muscle glucose uptake. NCRAE provokes an increase of insulin release and glucose uptake without any effect on hepatic glycogenolysis. We could also show that none of these compounds implicates hepatic glucose 6-phosphatase in contrast to chlorogenic acid, known as an inhibitor of glucose 6-phosphatase and which is able to decrease glucose output from hepatocytes. Our results point out that NCRAE is able to decrease blood glucose without any effect hepatic effect. Our in vivo experiments bring evidence that 4 daily IP administrations of NCRAE improve IP glucose tolerance in a dose-dependent manner and mainly via an insulin sensitizing effect.

Conclusions

We conclude that NCRAE presents an antihyperglycemic effect essentially due to a peripheral effect on muscle glucose uptake.     

Sarcopoterium spinosum extract as an antidiabetic agent: In vitro and in vivo study

Ethnopharmacological relevance

Sarcopoterium spinosum (L.) sp., a common plant in the Mediterranean region, is widely used as an antidiabetic drug by Bedouin healers. However, the antidiabetic properties of Sarcopoterium spinosum had not been fully validated using scientific tools.

Aim of the study

To determine the effectiveness of Sarcopoterium spinosum extract as an antidiabetic agent in vitro and in vivo.

Materials and methods

RINm pancreatic β-cells, L6 myotubes, 3T3-L1 adipocytes and AML-12 hepatocytes were treated with an aqueous Sarcopoterium spinosum extract (0.001–10 mg/ml). The effect of the extract on specific physiological functions, including insulin secretion, pancreatic β-cell viability, GSK3β phosphorylation, lipolysis and glucose uptake was measured. In vivo studies were performed using KK-A^y mice, given the extract for several weeks. IPGTT was performed, and plasma insulin, FFA, food consumption and body weight were measured. In addition, diabetic KK-A^y mice were given a single dose of the extract, and IPGTT was performed.

Results

Sarcopoterium spinosum extract increased basal and glucose/forskolin-induced insulin secretion in RINm cells, and increased cell viability. The extract inhibited lipolysis in 3T3-L1 adipocytes, and induced glucose uptake in these cells as well as in AML-12 hepatocytes and L6 myotubes. GSK3β phosphorylation was also induced in L6 myotubes, suggesting increased glycogen synthesis. Sarcopoterium spinosum extract had a preventive effect on the progression of diabetes in KK-A^y mice. Catechin and epicatechin were detected in Sarcopoterium spinosum extract using hyphenated LC–MS/MS.

Conclusions

Sarcopoterium spinosum extract has effects that mimic those of insulin and provide the basis for antidiabetic activity of the extract.     

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.     

The basis for the antihyperglycemic activity of Indigofera arrecta in the rat

The basis for the antihyperglycaemic property of Indigofera arrecta, a plant used for the treatment of diabetes, was evaluated using normoglycemic and streptozotocin-induced diabetic rats. The rats were given different doses of the freeze-dried extract of the plant material orally and intraperitoneally. The extract decreased the plasma glucose levels of fasting normoglycemic rats, but did not prevent the rise in plasma glucose after an oral glucose load in these rats. The extract increased plasma insulin levels. In the diabetic rats, the rise in blood glucose after an oral glucose load was not affected when the extract was administered 17 days after induction of diabetes. When administered 7 days after induction of diabetes, the rise in blood glucose was decreased, and was stabilized after 30 min. The results indicate that I. arrecta is insulinotropic, requiring functional beta cells to express its effect.     

Cornus kousa F.Buerger ex Miquel increases glucose uptake through activation of peroxisome proliferator-activated receptor γ and insulin sensitization

Aim of the study

Cornus kousa F.Buerger ex Miquel, an oriental medicinal plant, has been traditionally used for the treatment of hyperglycemia, but its molecular mechanism remains unknown. The goal of this study was to investigate the peroxisome proliferator-activated receptor γ (PPARγ) ligand-binding activity of Cornus kousa and to determine the effects of Cornus kousa on insulin sensitization in 3T3-L1 cells for the treatment of type 2 diabetes.

Materials and methods

PPARγ luciferase transactivation assay was used to evaluate the PPARγ ligand-binding activity of Cornus kousa leaf extract. Western blot analysis, oil Red O staining, and glucose uptake assay were performed to evaluate PPARγ agonistic activity and insulin sensitizing effects of Cornus kousa leaf extract (CKE) in 3T3-L1 cells.

Results

CKE increased PPARγ ligand-binding activity in a dose-dependent manner. In addition, CKE enhanced adipogenesis and the expression of PPARγ target proteins, including glucose transporter 4 (GLUT4) and adiponectin, as well as proteins involved in adipogenesis, including PPARγ and CCAAT/enhancer binding protein α (C/EBPα) in 3T3-L1 adipocytes. Furthermore, CKE led to significant induction of glucose uptake and stimulated insulin signaling, but not to activation of AMP-activated protein kinase (AMPK) signaling. The enhanced glucose uptake by CKE were abolished by treatment with bisphenol a diglycidyl ether (BADGE), a PPARγ antagonist, or LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), but not by compound C, an AMPK inhibitor.

Conclusion

Consistent with the high PPARγ ligand-binding activity, CKE increased glucose uptake through PPARγ activation and insulin signaling. These results suggest that CKE could have pharmacological effects for the treatment of hyperglycemia and type 2 diabetes.     

Effects of an n-butanol extract from the stem of Tinospora crispa on blood pressure and heart rate in anesthetized rats

Ethnopharmacological relevance

Tinospora crispa has been used in folkloric medicine for control of blood pressure, as an antipyretic, for cooling down the body temperature and for maintaining good health.

Aim of the study

To investigate the effects and mechanisms of action of an n-butanol extract from the stems of Tinospora crispa (T. crispa extract) on blood pressure and heart rate in anesthetized rats.

Materials and methods

Air-dried stems of T. crispa were extracted with water, followed by partitioned extract with chloroform, ethyl acetate, and finally by n-butanol. The n-butanol soluble part was evaporated under reduced pressure and lyophilization to obtain a crude dried powder (T. crispa extract). The effects and mechanisms of the T. crispa extract on blood pressure and heart rate were studied in anesthetized normal and reserpinized rats in vivo in the presence of different antagonists.

Results

T. crispa extract (1-100 mg/kg, i.v.) caused a decrease in mean arterial blood pressure (MAP) and this effect was inhibited by propranolol, phentolamine, atenolol and/or the β₂-antagonist ICI-118,551, but not by atropine or hexamethonium. In reserpinized rats, the T. crispa extract had a dual effect: reduction in hypotensive activity, followed by a small increase in blood pressure. The decrease in MAP in reserpinized rat was slightly potentiated by phentolamine, but inhibited by propranolol or ICI-118,551 only if atenolol and phentolamine were also present. The increase in MAP was potentiated by propranolol and ICI-118,551, but was inhibited by phentolamine. The T. crispa extract had a dual effect on heart rate in the normal rat: a small transient decrease, followed by an increase in heart rate. The positive chronotropic effect of T. crispa extract was inhibited by propranolol, phentolamine and atenolol, but not by ICI-118,551, atropine or hexamethonium. Reserpine potentiated the positive chronotropic effect of the T. crispa extract and this effect was inhibited by propranolol, atenolol and ICI-118,551, but not by phentolamine.

Conclusions

From these results we suggest that T. crispa extract possesses at least three different cardiovascular-active components that act directly via (1) β₂-adrenergic receptors to cause a decrease in blood pressure, and β₁- and β₂-adrenergic receptors to cause an increase in heart rate, (2) α-adrenergic receptors to cause an increase in blood pressure and heart rate, and (3) a non-adrenergic and non-cholinergic pathway to cause a decrease in MAP and heart rate. These findings provide scientific support for the tradition of using this plant to modify the actions of the human cardiovascular system.     

The Significance of Tinospora crispa in Treatment of Diabetes Mellitus

Tinospora crispa is a medicinal plant belonging to the botanical family Menispermiaceae. The plant is widely distributed in Southeast Asia and the northeastern region of India. A related species Tinospora cordifolia is used in Ayurveda for treating a large spectrum of diseases. Traditional healers of Thailand, Malaysia, Guyana, Bangladesh and the southern Indian province of Kerala use this plant in the treatment of diabetes. Many diterpenes, triterpenes, phytosteroids, alkaloids and their glycosides have been isolated from T. crispa. Cell culture and animal studies suggest that the herb stimulates secretion of insulin from β‐cells. It also causes dose‐dependent and time‐dependent enhancement of glucose uptake in muscles. However, in view of the reported hepatotoxicity, this herb may be used with caution. This article reviews the animal studies and human clinical trials carried out using this herb. Areas of future research are also identified. Copyright © 2016 John Wiley & Sons, Ltd.     

Korean red ginseng stimulates insulin release from isolated rat pancreatic islets

Ethnopharmacological relevance

Korean red ginseng (KRG), one of heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has a long history as herbal remedy for antidiabetic effect.

Aim of the study

The effect and mechanism of KRG on stimulation of insulin release were investigated in isolated rat pancreatic islets.

Material and methods

Pancreatic islets isolated from rats were used to evaluate the insulinotropic action of KRG. The effect of Ca on the insulinotropic action of KRG was investigated.

Results

The aqueous ethanolic extract of KRG (AEE-KRG) (0.1–1.0 mg/ml) significantly evoked a stimulation of insulin release at 3.3 mM glucose compared to the control. Experiments at different glucose concentrations (8.4 and 16.7 mM) showed that AEE-KRG significantly stimulated on its own whereas it did not potentiate insulin secretion induced by glucose. The extracellular Ca²⁺-free condition, a L-type Ca²⁺ channel blocker and an ATP-sensitive K⁺ channel opener significantly inhibited insulin secretion evoked by AEE-KRG.

Conclusion

These findings suggest that KRG displays beneficial effects in the treatment of diabetes at least in part via the stimulation of insulin release in a glucose-independent manner.     

Antidiabetic Properties and Mechanism of Action of Orthosiphon stamineus Benth Bioactive Sub-fraction in Streptozotocin-induced Diabetic Rats

Orthosiphon stamineus is a popular folk medicine widely used to treat many diseases including diabetes. Previous studies have shown that the sub-fraction of chloroform extract was able to inhibit the rise of blood glucose levels in a glucose tolerance test. This study was carried out to evaluate the chronic effect and possible mechanism of action of the bioactive chloroform sub-fraction of O. stamineus using streptozotocin-induced diabetic rats and in vitro methods. Administration of the chloroform extract sub-fraction 2 (C?2-b) at a dose of 1 g/kg twice daily on diabetic rats for 14 days showed a significant lowering (p < 0.05) of the final blood glucose level compared to the pretreatment level. However, there were no significant differences in the plasma insulin levels post-treatment compared to the pretreatment levels for all doses of C?2-b. Conversely, C?2-b at a concentration of 2 mg/mL significantly increased (p < 0.001) the glucose uptake by the rat diaphragm muscle. The increase in glucose uptake was also shown when the muscle was incubated in a solution containing 1 IU/mL of insulin or 1 mg/mL of metformin. Furthermore, the effect of this sub-fraction on glucose absorption in the everted rat jejunum showed that C?2-b at concentrations of 0.5 mg/mL, 1 mg/mL and, 2 mg/mL significantly reduced the glucose absorption of the jejunum (p < 0.05–0.001). Similarly, the absorption of glucose was also inhibited by 1 mg/mL and 2 mg/mL of metformin (p < 0.001). These results suggest that the effect of C?2-b may be due to extra-pancreatic mechanisms. There was no evidence that the plant extract stimulated the release of insulin in order to lower the blood glucose level.     

Anti-diabetic effects of Sutherlandia frutescens in Wistar rats fed a diabetogenic diet

Sutherlandia frutescens has been marked as a potential hypoglycaemic agent for the treatment of type 2 diabetes. We investigated the effects of Sutherlandia frutescens in bringing about hypoglycaemia and promoting glucose uptake in pre-diabetic rats. Crushed Sutherlandia frutescens leaves in drinking water were administered to rats fed a high fat diet. Positive control rats received only metformin. Glucose uptake experiments were undertaken using [(3)H] deoxy-glucose. Various physiological parameters were also measured. Rats receiving Sutherlandia frutescens displayed normoinsulinaemic levels, after 8 weeks medicational compliance, compared to the fatty controls. There was a significant increase in glucose uptake into muscle and adipose tissue, and a significant decrease in intestinal glucose uptake (p<0.001 at 60min) in rats receiving the plant extract. The Sutherlandia frutescens plant extract shows promise as a type 2 anti-diabetes medication because of its ability to normalize insulin levels and glucose uptake in peripheral tissues and suppress intestinal glucose uptake, with no weight gain noted. The exact mechanism of action and the extract's efficacy in humans need further confirmation.     

当药黄素治疗2型糖尿病的作用机制及研究进展

2型糖尿病（type 2 diabetes mellitus,T2DM）是一种由多因素导致的系统代谢紊乱疾病,可能由胰岛β细胞的胰岛素分泌缺陷、肌肉组织对葡萄糖的摄取减少、肝糖原输出量增加、脂代谢紊乱、肠促胰岛素效应减弱、肾脏对葡萄糖的处理失调和神经递质紊乱等造成。目前,T2DM的治疗机制主要是通过增加胰岛素的分泌,减少肝糖原的输出,抑制肠道葡萄糖的摄取和吸收,改善C肽的分泌来实现。当药黄素是酸枣仁、菥蓂和淡竹叶等的主要活性成分之一,可诱导干细胞分化成胰岛素产生细胞,调节胰岛素分泌、干预肌肉组织和肝糖原的代谢过程,抑制糖脂和神经递质代谢紊乱,抑制炎症和氧化应激反应的发生,此外还有抗炎、抗氧化、增强记忆力等作用。通过查阅近年来国内外当药黄素治疗T2DM的作用机制,对其分析归纳整理,为T2DM的治疗和研究提供科学的理论依据。     

Glucose uptake-stimulatory activity of Amomi Semen in 3T3-L1 adipocytes

Amomi Semen has been used as a folk remedy for the treatment of diabetes in Korea. The aim of this study was to examine whether it had an enhancing effect on glucose uptake, an essential process of insulin action. Its aqueous ethanolic extract significantly stimulated glucose uptake in 3T3-L1 adipocytes at the concentration of 0.5 mg/ml. The extract significantly potentiated insulin-stimulated glucose uptake with a dose-dependent manner at a concentration range from 0.02 to 0.5 mg/ml. The results suggest that the antidiabetic action of Amomi may be mediated through the stimulation of glucose uptake and the potentiation of insulin action.     

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

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

Investigation of antihyperglycaemic activity of aqueous and petroleum ether extract of stem bark of Pongamia pinnata on serum glucose level in diabetic mice

Aim of the study

The aim of the study was to evaluate the antihyperglycaemic activity of aqueous (PPSB-AQE) and petroleum ether (PPSB-PEE) extract of stem bark Pongamia pinnata in alloxan induced diabetic mice.

Materials and methods

Diabetes was induced in mice by alloxan (80 mg/kg, i.v.). After acute and subacute treatment serum glucose was determined. OGTT was performed in PPSB-PEE pretreated animals.

Results

PPSB-PEE (25, 50, 100, 200 and 400 mg/kg) showed significant reduction in serum glucose level in acute and subacute studies. The antihyperglycaemic effects of PPSBPE (100, 200 and 400 mg/kg) showed onset at 2 h and peak effect at 6 h and the effect was sustained until 24th h with 400 mg/kg. In subacute study, antihyperglycaemic effect was observed on 21st day. In PPSBPE treated mice the body weight was not reduced in contrast to that in vehicle group. In OGTT, increased glucose utilization was observed.

Conclusions

It is concluded that PPSB-PEE but not PPSB-AQE showed antihyperglycaemic activity.     

Bioactivity studies and chemical profile of the antidiabetic plant Genista tenera

Aim of the study

Genista tenera is a plant endemic to the island of Madeira and is used in folk medicine to control diabetes. In the present work we evaluate the antihyperglycaemic activity of its n-butanol extract and determine its chromatographic profile. In addition, this extract, the ethyl acetate and diethyl ether plant extracts were studied in order to assess the plant antioxidant and acetylcholinesterase inhibitory activities, as well as its cyto- and genotoxicities.

Materials and methods

HPLC-DAD-ESI-MS was used to analyze the flavonoid profile of the n-butanol extract. The antihyperglycaemic activity of this extract was performed over streptozotocin induced diabetic Wistar rats (200 mg/kg, bw/day), for 15 days. Antioxidant activity (DPPH assay) and acetylcholinesterase inhibitory effect (Ellman method) were also performed. Acute cytotoxicity and genotoxicity were assessed by proliferative index quantification and the short-term chromosomal aberration technique, after exposure of lymphocytes to the extracts.

Results and conclusions

The n-butanol extract, where 21 monoglycosyl and 12 diglycosyl flavonoids were detected, significantly lowered blood glucose levels, bringing them to normal values after 15 days of treatment. The best radical scavenging activity was observed for the ethyl acetate extract (48.7% at 139.1 μg/mL), which was also the most effective one at the minimal concentration tested. The highest acetylcholinesterase inhibitory activity (77.0% at 70.0 μg/mL) was also obtained with the ethyl acetate extract. In vitro toxicity studies showed no evidence for acute cytotoxicity or genotoxicity. This is the first report on antidiabetic activity of genus Genista.     

Anti-diabetic and anti-cataract effects of Chromolaena odorata Linn., in streptozotocin-induced diabetic rats

Ethnopharmacological relevance

Chromolaena odorata Linn., is used in traditional Indian medicine in the treatment of diabetes and eye problems.

Aim of the study

The present study was designed to investigate the effect of the ethanol extract Chromolaena odorata leaves (ACO) in streptozotocin (STZ; 45 mg/kg, i.v) induced diabetes and cataract in rats.

Materials and methods

Different doses of ACO (200 and 400 mg/kg) was administered once daily for eight weeks to STZ-induced diabetic rats. To know the mechanism of action of title plant, AUC_glucose, AUC_insulin, Homeostatic Model Assessment (HOMA), insulin tolerance test (ITT) and glucose uptake by rat hemi-diaphragms were carried out. Further, cataract score was taken once in a week upto eight weeks and opacity index was measured. HPLC fingerprinting profiling of ACO was also carried out.

Results

Administration of ACO exhibited significant reduction in glucose, HOMA, lipid profiles and significantly improved glucose and insulin tolerance, glycogen content, glucose uptake by skeletal muscle, serum insulin and HDL-c levels. In addition, ACO also decreased oxidative stress by improving endogenous antioxidants. Further, treatment of ACO showed significantly reduced onset and extent of cataract.

Conclusion

The present data suggested that the treatment of ACO reversed the STZ-induced diabetes and cataract in rats. The observed beneficial effects may be mediated by interacting with multiple targets operating in diabetes mellitus and its complication. Taken together, this study provided the scientific evidence for the traditional use of Chromolaena odorata.     

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.