Target screening and antihyperglycemic activity on SGLT2 and α-glucosidase in vitro and in vivo of TSG from Polygonum multiflorum / 中草药

Objective: To study the mechanism that TSG can reduce plasma glucose level by inhibiting sodium-dependent glucose cotransporters 2 (SGLT2) and α-glucosidase in vitro and in vivo. Methods: Molecular docking method was used to study the binding affinities of TSG and diabetes related targets. The structures of targets were taken from Protein Data Bank or references. 1-NBDG and PNPG were used as the substrates for the inhibition assays of TSG against SGLT2 and α-glucosidase respectively in vitro. The antihyperglycemic activity of TSG was operated by oral glucose tolerance test (OGTT) and urinary glucose excretion (UGE) test in rats. Results: TSG was identified as the inhibitors of SGLT2 with the docking score of -9.35 less than -9.79 of dapagliflozin as the positive control and α-glucosidase with the docking score of -5.44 compared to -5.58 of acarbose as the positive control. TSG showed the inhibitory rate of 21.6% at the dose of 10 μmol/L against SGLT2 and 32.5% at the dose of 100 μmol/L in vitro test. Compared with model group, the group of 120 mg/kg dose had significant difference (P < 0.05) but the overall effect was not as strong as dapagliflozin in OGTT and UGE test. The result of rat in vivo test showed that glucose inhibition rate of TSG (120 mg/kg) was (9.3 ± 1.0)%, urinary glucose content was (435.5 ± 84.0) mg/kg, which showed certain hypoglycemic effect. Conclusion: TSG exhibited antiglycemic activity through inhibiting SGLT2 and α-glucosidase, which was considered to be a new lead compound of dual target inhibitors.

Identification of AMPK activator from twelve pure compounds isolated from Aralia Taibaiensis: implication in antihyperglycemic and hypolipidemic activities

The root bark extract of Aralia taibaiensis is used traditionally for the treatment of diabetes mellitus in China. The total saponin extracted from Aralia Taibaiensis (sAT) has effective combined antihyperglycemic and hypolipidemic activities in experimental type 2 diabetic rats. However, the active compounds have not yet been fully investigated. In the present study, we examined effects of twelve triterpenoid saponins on AMP-activated protein kinase (AMPK) activation, and found that compound 28-O-β-D-glucopyranosyl ester (AT12) significantly increased phosphorylation of AMPK and Acetyl-CoA carboxylase (ACC). AT12 effectively decreased blood glucose, triglyceride (TG), free fatty acid (FFA) and low density lipoprotein-cholesterol (LDL-C) levels in the rat model of type 2 diabetes mellitus (T2DM). The mechanism by which AT12 activated AMPK was subsequently investigated. Intracellular ATP level and oxygen consumption were significantly reduced by AT12 treatment. The findings suggested AT12 was a novel AMPK activator, and could be useful for the treatment of metabolic diseases.

Antidiabetic Potential of Potentilla fulgens Roots in Validated Animal Models of Diabetes

The present study was undertaken to investigate the antidiabetic potential of tap roots of Potentilla fulgens in streptozotocin induced diabetic rat models. The crude powder, ethanolic, ethanolic: aqueous and aqueous extracts of tap roots were administered to normoglycemic- and streptozotocin (STZ)-induced diabetic rats in a single dose study. The ethanolic extract showed significant improvement in oral glucose tolerance and antihyperglycemic effect on sucrose loaded normal rats and STZ-induced diabetic rats. Of the isolated aqueous, n-butanol, chloroform and n-hexane soluble fractions of the active ethanolic extract of the roots, the aqueous fraction (100 mg/kg body weight) showed significant blood glucose lowering effect on STZ-induced diabetic rats. In a multiple dose study, aqueous fraction of ethanolic extract of P. fulgens roots significantly improved the body weight, percent glycated hemoglobin (%HbA1c), fasting blood glucose, oral glucose tolerance (OGTT), serum insulin, lipid profile, liver and kidney parameters in STZ-induced diabetic rats. The aqueous fraction also showed marked improvement in OGTT and serum insulin level in neonatal STZ-induced diabetic rats for 30 consecutive days. The aqueous fraction of the roots also inhibited the activity of alpha (α)-glucosidase enzyme in a dose dependent manner. In conclusion, the finding suggested that an aqueous fraction of tap roots of P. fulgens possessed potential antidiabetic activity.

In vivo potential hypoglycemic and in vitro vasorelaxant effects of Cecropia glazioviistandardized extracts

ABSTRACTThe aim of this study is to investigate the effect of Cecropia glaziovii Snethl, Urticaceae, extracts on the oral glucose tolerance curve, on glycemia in alloxan-induced diabetic rats and vasorelaxant effect after the extraction process, and to standardize the extractive solutions. The effects of the process variables and their interactions were calculated in relation to dry residue, pH, total phenolic results and chemical marker content. Furthermore, the effect of the extracts (400 mg/kg), chlorogenic (2 or 15 mg/kg) and caffeic acids (2 mg/kg) were investigated on the oral glucose tolerance curve and on glycemia in alloxan-induced diabetic rats. Oral administration of ethanol extracts 4d20 and 8d20 significantly improved glucose tolerance in the hyperglycemic rats. Chlorogenic and caffeic acids, as well as the association of the compounds were able to significantly reduce glycemia after oral gavage treatments. On the other hand, the aqueous extracts did not alter the glycemia. The aqueous extracts (8020 and 9030) and only the higher dose of chlorogenic acid presented a significant effect on serum glucose lowering in diabetic rats. Additionally, the IC50 reveals that the ethanol extracts presented more potent vasodilator effects than the aqueous extracts in aortic rings. This study shows that C. glazioviistandardized extracts exhibits antihyperglycemic action, is able to improve glucose tolerance and has a potent vascular relaxing effect. These results are probably linked to concentrations of the main phenolic compounds of the extracts.

Antidiabetic and Antioxidant potential of Andrographis paniculata Nees. leaf ethanol extract in streptozotocin induced diabetic rats.

This study aimed to elucidate the potential of Andrographis paniculata (leaves) both as an antidiabetic and as an antioxidant in streptozotocin induced diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin. After grouping, diabetic rats were administered the leaf ethanol extract (250 and 500 mg/kg b.w.) for 28 days. Fasting blood glucose, body weight, creatinine and urea levels and histopathological study of pancreas were carried out to evaluate the antidiabetic effects. Enzyme activity of superoxide dismutase, catalase and glutathione peroxidase in the liver homogenate was assayed. After the treatment with A. paniculata leaf extract, fasting blood glucose, creatinine and urea levels were found to be decreased in diabetic rats.The extract was found to be non toxic as seen by the normal creatinine and urea levels in the extract fed normal rats. There was an increase in the activity of liver antioxidant enzymes in diabetic treated rats. Histopathological study of pancreas revealed the islet cell restoring and regenerative ability of A. paniculata extract. According to our present findings, A. paniculata leaves possessed significant antihyperglycemic and antioxidant effect in streptozotocin induced diabetic rat which might be due to its islet cell restoring and regenerative ability as well as the upregulation of antioxidant enzymes.

Antihyperglycemic Effect of Various Fractions from Residues of Blumea balsamifera / 中草药·英文版

Objective: To evaluate the antihyperglycemic activities of various fractions from the residues of Blumea balsamifera (BB), and to properly utilize the waste resource. Methods: The antihyperglycemic activities were evaluated by the suppression on serum glucose level in vivo and α-glucosidase inhibition assay in vitro. The high-, mid-, and low-dose (1, 0.5, and 0.25 g/kg of the herb) fractions were ig given to mice for 8 d. The serum glucose was monitored at 1 and 12 h after feeding. Results: The fasting and postprandial serum glucose levels of mice treated with high-dose petroleum ether fraction, ethyl acetate fraction, butyl alcohol fraction, methanol fraction, and water extract from BB were 4.45, 4.39, 4.43, 4.15, 3.74 mmol/L and 6.98, 6.23, 6.45, 6.26, 5.88 mmol/L, respectively, while those in vehicle control group were 5.63 and 7.50 mmol/L. There are four different inhibiting manners by the results of α-glucosidase inhibition assay. Conclusion: The residues of BB have anti-diabetes activities after steam distillation. © 2014 Tianjin Press of Chinese Herbal Medicines.

Phytochemical screening and antihyperglycemic activity of Heliotropium indicum whole plant in Streptozotocin induced diabetic rats.

Present study was designed to screen phytochemical constituents and antihyperglycemic activity of Heliotropium indicum (HI) in Streptozotocin (STZ) induced diabetic rats. Heliotropium indicum (Boraginaceae) whole plant is used as traditional medicine for a number of ailments including diabetes. The whole plant was collected, shade dried and extracted with different solvents in the increasing order of polarity. When different solvent extracts of HI each at a dose of 500 mg/kg bw were given to diabetic rats, the methanol and aqueous extracts produced significant (P<0.0001) antidiabetic activity. Phytochemical screening of various solvent extracts of HI whole plant revealed the presence of alkaloids, steroids, triterpenes, saponins and tannins. When methanol active fraction of Heliotropium indicum (MAFHI) was checked for its antidiabetic activity, the fraction at dose of 750 mg/kg bw produced marked antihyperglycemic activity. The antihyperglycemic activity was also exhibited during oral glucose tolerance test (OGTT) with the same dosage of MAFHI.

Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice.

Antihyperglycemic activity of compounds isolated from Indian medicinal plants.

Eleven antidiabetic Indian medicinal plants were investigated in streptozotocin induced diabetic rat model and provided scientific validation to prove their antihyperglycemic activity. Antidiabetic principles from five plants were isolated. All the compounds isolated were evaluated for antihyperglycemic activity in streptozotocin induced diabetic rat model and activities were compared with standard drug metformin. Some compounds were also screened in db/db mice. Two compounds (PP-1 and PP-2) inhibited significantly the activity of PTPase-1B in an in vitro system. This might be the underlying mechanism of antihyperglycemic activity of these compounds.