Oral Sucrose Tolerance Test Research Articles

Antihyperglycemic Activity of the Leaves from Annona cherimola Miller and Rutin on Alloxan-induced Diabetic Rats.

Background:Annona cherimola, known as “chirimoya” has been reported in Mexican traditional medicine for the treatment of diabetes.Objective:The aims of the present study were to validate and assess the traditional use of A. cherimola as an antidiabetic agent.Materials and Methods:The ethanol extract from A. cherimola (300 mg/kg, EEAc), subsequent fractions (100 mg/kg), and rutin (30 mg/kg) were studied on alloxan-induced type 2 diabetic (AITD) and normoglycemic rats. In addition, oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) were performed in normoglycemic rats. Molecular docking technique was used to conduct the computational study.Results:Bioassay-guided fractionation of EEAc afforded as major antihyperglycemic compound, rutin. EEAc attenuated postprandial hyperglycemia in acute test using AITD rats (331.5 mg/dL) carrying the glycemic levels to 149.2 mg/dL. Rutin after 2 h, attenuated postprandial hyperglycemia in an acute assay using AITD rats such as EEAc, with maximum effect (150.0 mg/dL) being seen at 4 h. The antihyperglycemic activities of EEAc and rutin were comparable with acarbose (151.3 mg/dL). In the subchronic assay on AITD rats, the EEAc and rutin showed a reduction of the blood glucose levels since the 1st week of treatment, reaching levels similar to normoglycemic state (116.9 mg/kg) that stayed constant for the rest of the assay. OGTT and OSTT showed that EEAc and rutin significantly lowered blood glucose levels in normoglycemic rats at 2 h after a glucose or sucrose load such as acarbose. Computational molecular docking showed that rutin interacted with four amino acids residues in the enzyme α-glucosidase.Conclusion:The results suggest that rutin an α-glucosidase inhibitor was responsible in part of the antihyperglycemic activity of A. cherimola. Its in vivo antihyperglycemic activity is in good agreement with the traditional use of A. cherimola for the treatment of diabetes.SUMMARYThe ethanol extract from Annona cherimola (300 mg/kg, EEAc), subsequent fractions (100 mg/kg) and rutin (30 mg/kg) were studied on alloxan-induced type 2 diabetic (AITD) and normoglycemic rats. The results suggest that rutin; an α-glucosidase inhibitor was responsible in part of the antihyperglycemic activity of A. cherimola. Its in vivo antihyperglycemic activity is in good agreement with the traditional use of A. cherimola for the treatment of diabetes.Abbreviations Used: EEAc: The ethanol extract from Annona cherimola, AITD: Alloxan-induced type 2 diabetic rats, OGTT: Oral glucose tolerance test, OSTT: Oral sucrose tolerance test, DM: Diabetes mellitus

Antidiabetic and Antihyperalgesic Effects of a Decoction and Compounds from Acourtia thurberi.

The purpose of this research was to examine the preclinical efficacy of a decoction from the roots of Acourtia thurberi as a hypoglycemic, antihyperglycemic, and antihyperalgesic agent using well-known experimental models in mice. Acute oral administration of A.thurberi decoction did not produce toxic effects in mice, according to the Lorke procedure. A.thurberi decoction (31.6-316.2 mg/kg, p. o.) decreased blood glucose levels during acute hypoglycemic and the oral glucose tolerance and oral sucrose tolerance tests, both in normoglycemic and hyperglycemic animals. Phytochemical analysis of A.thurberi roots led to the isolation of perezone (1), a mixture of α-pipitzol (2) and β-pipitzol (3), and 8-β-D-glucopyranosyloxy-4-methoxy-5-methyl-coumarin (4). A pharmacological evaluation of compounds 1-4 (3.2-31.6 mg/kg) using the same assays revealed their hypoglycemic and antihyperglycemic actions. Finally, local administration of A.thurberi decoction (31.6-316.2 µg/paw) and compounds 1-4 (3.2-31.6 µg/paw) produced significant inhibition on the licking time during the formalin test in healthy and hyperglycemic mice, demonstrating their antinociceptive and antihyperalgesic potential, respectively. Altogether, these results could be related to the use of A.thurberi for treating diabetes and painful complaints in contemporary Mexican folk medicine. A suitable UPLC-ESI/MS method was developed and successfully applied to quantify simultaneously compounds 1 and 4 in A.thurberi decoction.

Alkaloids from the Fungus Penicillium spathulatum as α-Glucosidase Inhibitors.

Benzomalvin A (1), quinolactacins A1 (2), A2 (3) and B (4), quinolonimide (5), asperphenamate (6), and a new halogenated polyhydroxyanthraquinone, namely 2-chloro-6-[2'(S)-hydroxypropyl]-1,3,8-trihydroxy-anthraquinone (7), were isolated from an organic extract obtained from the solid culture of Penicillium spathulatum B35. Compounds 2 and 3 were isolated as an epimeric mixture, and compound 4 as a racemate. The structure of 7 was elucidated using 1D and 2D NMR, combined with computational methods (density functional theory). Compound 1, the mixture of 2 and 3, racemate 4, and compound 6 inhibited the yeast α-glucosidase in a concentration-dependent fashion with IC50 values of 383.2, 273.3, 57.3, and 8.3 µM, respectively. The α-glucosidase inhibitory properties of 1 were confirmed in vivo with an oral sucrose tolerance test in normal and hyperglycemic mice (p < 0.05). Furthermore, docking studies predicted that the most stable conformers of 1 bind to yeast and mammalian α-glucosidases with a higher affinity than acarbose. Finally, 1 also showed antihyperalgesic activity when tested in the formalin assay in hyperglycemic mice (p < 0.05).

Inhibitory actions of Pseuderanthemum palatiferum (Nees) Radlk. leaf ethanolic extract and its phytochemicals against carbohydrate-digesting enzymes

ObjectiveTo investigate the effects of the leaf ethanolic extract of Pseuderanthemum palatiferum (PPE) and its isolated phytochemicals, stigmasterol and sitosterol-3-O-β-d-glucopyranoside, against α-amylase and α-glucosidase enzyme activities both in vitro and in vivo. MethodsA concentration of maltose, which is a product released in α-amylase-catalyzing reaction, was used as an index of in vitro α-amylase activity. Meanwhile, in vitro α-glucosidase enzyme activity was indicated by the amount of liberated p-nitrophenol in α-glucosidase-catalyzing reaction. In vivo α-amylase and α-glucosidase enzyme activities were evaluated in the normal rats by using oral starch tolerance test and oral sucrose tolerance test, respectively. ResultsPPE exerted a concentration-dependent inhibitory action against both α-amylase and α-glucosidase in vitro with the IC50 values of (11.79 ± 8.10) mg/mL and (1.00 ± 0.11) mg/mL, respectively. Stigmasterol and sitosterol-3-O-β-d-glucopyranoside also exerted an in vitro α-amylase inhibition with the IC50 values of (59.41 ± 8.22) μg/mL and (111.19 ± 9.02) μg/mL, respectively. However, these phytochemicals did not produce a concentration-dependent inhibition against in vitro α-glucosidase activity. PPE and its isolated phytochemicals significantly decreased the blood glucose levels at t = 30 min in the oral starch tolerance test. From the sucrose tolerance test, only PPE but not its isolated phytochemicals significantly caused a depletion in the blood glucose levels at t = 30 min ConclusionsThese results indicate an inhibitory action against carbohydrate-digesting enzymes as the anti-diabetic mechanism of action of PPE. Nonetheless, further clinical study is required to justify its role in the treatment of diabetes.

Discovery of xanthine oxidase inhibitors and/or α-glucosidase inhibitors by carboxyalkyl derivatization based on the flavonoid of apigenin

Three series of apigenin derivatives have been prepared by coupling the carboxyl alkyl group to 4'-, 5- or 7-hydroxyl groups of apigenin respectively. Preliminary biological evaluation in vitro revealed that xanthine oxidase inhibitory activity was improved by modifications at 4'-position and decreased by similar modifications at 5-, 7-positions while α-glucosidase inhibitory activity was maintained by modifications at 5-, 7-positions but lost by modifications at 4'-position. Administration (ip) of 7e markedly lowered serum uric acid levels in potassium oxonate induced hyperuricemic mouse model and administration (p.o.) of 11d or 11e effectively suppressed the elevation of serum glucose in the oral sucrose tolerance test in mice, while apigenin were not significantly effective in both tests.

Effect of sucrose consumption on serum insulin, serum cortisol and insulin sensitivity in migraine: Evidence of sex differences

The aim of this study was to compare the effect of sucrose on biomarkers of energy metabolism and utilization in migrainous men and women. A total of 20 participants (7=Migraine (female), 5=Migraine (male), 8=Non-migraine control) submitted to an oral sucrose tolerance test (OSTT), which required them to fast for 15h overnight and then ingest 75g sucrose dissolved in 175g water at 9 AM the next morning. Blood sampling for the assessment of serum insulin, serum cortisol and plasma glucose was conducted upon arrival at 0900h and then at regular 15-min intervals across a 150-min period. Comparison of insulin sensitivity indexes that rely on fasting glucose and insulin data failed to find evidence of insulin resistance in migraineurs or controls. Prior to sucrose consumption the level of fasting serum cortisol at 0-min on average was significantly higher in migraineurs. However, no significant group differences in the level of fasting serum insulin and plasma glucose at 0-min were noted. Following sucrose consumption: the level of serum insulin was significantly higher in female migraineurs; the level of serum cortisol was significantly higher in male migraineurs; glucose/insulin (G/I) ratio was significantly higher in male migraineurs at 135-min and 150-min; insulin/cortisol (I/C) ratio was significantly different with the I/C ratio lower in male migraineurs and higher in female migraineurs; area under the curve (AUC) insulin was significantly different across groups with AUC insulin lower in male migraineurs and higher in female migraineurs; and AUC cortisol was significantly higher in male migraineurs. It was concluded that the effect of sucrose on biomarkers of energy metabolism and utilization in male and female migraineurs is not the same. Therefore, the factors underlying migraine pathogenesis in men and women may also be different.

Evaluation of Zanthoxylum Rhetsa (Roxb.) bark extract on hyperglycemia and hyperlipidemia in streptozotocin- induced rats

The present study was systematically undertaken to assess the antihyperglycemic, antihyperlipidemic and antioxidant activity of the methanolic (ZRM) and aqueous (ZRA) extracts of Zanthoxylum Rhetsa (Roxb.) bark. The hypoglycemic effect was evaluated in normal rats by oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) by comparing with the standard. Streptozotocin (STZ) was used to induce diabetes in rats. The study also included tolerance of oral glucose, estimation of serum insulin and insulin tolerance in diabetic rats. Lipid profile, in vivo, in vitro antioxidant activity and histopathological study were performed to support antihyperglycemic activity of title plant. OGTT performed in normoglycemic rats showed that ZRA (500mg/kg) and ZRM (500mg/kg) caused 25.03% and 26.57% reduction (P

Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity

Ethnopharmacological relevanceIt is said that black tea is effective against type 2 diabetes mellitus because it can help modulate postprandial hyperglycemia. However, the mechanism underlying its therapeutic and preventive effects on type 2 diabetes mellitus is unclear. In this study, we focused on the effect of black tea on the carbohydrate digestion and absorption process in the gastrointestinal tract. We examined whether black tea can modulate postprandial hyperglycemia. Materials and methodsThe freeze-dried powder of the aqueous extract of black tea leaves (JAT) was used for in vitro studies of α-amylase activity, α-glucosidase activity, and glucose uptake by glucose transporters in Caco-2 cells; ex vivo studies of small intestinal α-glucosidase activity; and in vivo studies of oral sugar tolerance in GK rats, an animal model of nonobese type 2 diabetes mellitus. ResultsHalf maximal inhibitory concentration values indicated that JAT significantly reduced α-glucosidase activity, but weakly reduced α-amylase activity. Kinetic studies of rat small intestinal α-glucosidase activity revealed that the combination of JAT and the α-glucosidase inhibitor, acarbose, showed a mixed-type inhibition. JAT had no effect on the uptake of 2′-deoxy-d-glucose by glucose transporter 2 (GLUT2) and the uptake of α-methyl-d-glucose by sodium-dependent glucose transporter 1 (SGLT1). In the oral sucrose tolerance test in GK rats, JAT reduced plasma glucose levels in a dose-dependent manner compared with the control group. The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo. In contrast to the oral sucrose tolerance test, JAT showed no effect in the oral glucose tolerance test. ConclusionsJAT was demonstrated to inhibit the degradation of disaccharides into monosaccharides by α-glucosidase in the small intestine. Thereby indirectly preventing the absorption of the dietary source of glucose mediated by SGLT1 and GLUT2 transporters localized at the apical side of enterocytes in the small intestine. The results indicate that black tea could be useful as a functional food in the dietary therapy for borderline type 2 diabetes mellitus that could modulate postprandial hyperglycemia.

Hypoglycemic, antihyperglycemic, and antioxidant effects of the edible plant Anoda cristata

Ethnopharmacological relevanceSome studies refer that the entire plant of Anoda cristata is consumed as food and medicine; in particular for treating diabetes, inflammation, fever, cough, and wounds. The aim of this study was to establish the preclinical efficacy of Anoda cristata as hypoglycemic and/or antihyperglycemic agent using well-known animal models. Materials and methodsThe acute toxicity was analyzed by the Lorke method. Acute hypoglycemic as well as oral glucose and sucrose tolerance tests were used to determine the hypoglycemic and antihyperglycemic action of Anoda cristata. Several preparations of the plant, including a mucilage (M), an aqueous (T-AE), a free mucilage aqueous (FM-AE), and an organic (OE) extracts, were tested in healthy and NA-STZ-hyperglycemic mice. Glibenclamide (15mg/kg), acarbose (5mg/kg ) and metformin (200mg/kg) were used as positive controls. The major compounds acacetin (1) and diosmetin (2), isolated from an infusion of the plant applying chromatographic methods, were evaluated as hypoglycemic agents using the same assays. The FM-AE was tested also in rats with metabolic syndrome induced by a high-fructose fed. Finally some assays were performed to determine the antioxidant capacity of the FM-AE in vitro. ResultsThe results demonstrated that the extracts and compounds from Anoda cristata were effective for reducing blood glucose levels in healthy and NA-STZ-hyperglycemic mice when compared with vehicle groups (p<0.05). The FM-AE exerted also positive effect over different biochemical parameters altered in rats with metabolic syndrome induced by a fructose diet. FM-AE has also antioxidant action effectively trapping ONOO− and ROO• radicals. The major flavonoids isolated from the plant, namely acacetin (1) and diosmetin (2), caused significant hypoglycemic effect and possessed antioxidant activity. ConclusionAnoda cristata is effective to diminish glucose levels in vivo and to ameliorate different disorders related with the metabolic syndrome in rats. According to the results, the efficacy of Anoda cristata preparations could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases inhibitors, insulin secretagogues, glucose entrapment and radical trapping agents.

Antidiabetic property of Symplocos cochinchinensis is mediated by inhibition of alpha glucosidase and enhanced insulin sensitivity.

The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of ‘Nisakathakadi’ an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity.

Hypoglycemic properties of some preparations and compounds from Artemisia ludoviciana Nutt

Ethnopharmacological relevanceArtemisia ludoviciana, commonly known as “estafiate”, plays an important role in contemporary Mexico for treating several diseases including diabetes. To establish the preclinical efficacy of Artemisia ludoviciana as hypoglycemic and/or antihyperglycemic agent using well-known animal models. Materials and methodsAcute hypoglycemic as well as oral glucose (OGTT) and sucrose (OSTT) tolerance tests were used to demonstrate the value of the plant for treating diabetes. An essential oil (EO), an organic extract (OE) and an infusion (AE) were assayed in normal and NA-STZ-treated mice. The acute toxicity of the three preparations was analyzed by the Lorke method. The infusion was subjected to conventional phytochemical study using chromatographic conventional procedures. Some of the isolates were evaluated using the same pharmacological assays as well as an enzymatic test. The latter was employed to assess their potential inhibitory effect on yeast α-glucosidase. ResultsOral administration of OE to normal mice significantly decreased blood glucose level only at the dose of 100mg/kg; in NA-STZ-mice the hypoglycemic effect was observed at the three doses tested (31.6, 100, and 316mg/kg). The infusion reduced significantly, blood sugar levels only in diabetic mice; the best effect was observed at the dose of 316mg/kg. The EO was inactive when evaluated in normal mice. Regarding to the antihyperglycemic effect, the best effect was observed with the OE, during the OGTT and OSTT in diabetic mice. The infusion (AE) showed better effects during the OGTT in both normal and diabetic animals at the dose of 100mg/kg. Finally, the EO was inactive during an OGTT at the three doses tested (31.6, 100, and 316mg/kg) in diabetic mice. In addition, the results of AE on the enzymatic test using yeast α-glucosidase revealed an inhibition of 45%; this finding was consistent with the results obtained with the same preparation in vivo during an OSTT. Conventional phytochemical analysis of the active AE led to the isolation and characterization of eupatilin (1), jaceosidin (2), arglanin (3), salvinine (4), and 3,5-dicaffeoylquinic acid (5). Biological testing of 1 and 3 revealed their hypoglycemic effect. The hypoglycemic effect of arglanin (3) was attenuated in the presence of nicorandil, which suggested that the lactone behaved as an ATP-K+-channel blocker as glibenclamide. Salvinine (4) turned out to be a mixed α-glucosidase inhibitor, while 3 was inactive. ConclusionsArtemisia ludoviciana preparations showed hypoglycemic and antihyperglycemic effects, which could explain its effectiveness for treating diabetes in contemporary Mexico. Some of the active principles of the plant included compounds 1–5. These compounds seem to be acting synergistically on different molecular targets which involved glucose absorption and insulin liberation.

Postprandial glycaemia and inhibition of α-glucosidase activity by aqueous extract from Coriandrum sativum

The antihyperglycaemic properties of the aqueous extract from the leaves and stems of Coriandrum sativum L. were evaluated in normoglycaemic rats, and on α-glucosidase activity from Saccharomyces cerevisiae, in order to validate its use in folk medicine. In in vivo experiments rats were administered with the aqueous extract of the plant at 100, 300 and 500 mg/kg, to observe the effect on oral sucrose tolerance test. The aqueous extract exhibited significant antihyperglycaemic activity at the three tested doses. In vitro experiments with α-glucosidase exhibited a competitive-type inhibition. These results confirm the antidiabetic properties of the extract of C. sativum L., probably by the inhibition of α-glucosidase in the gastrointestinal tract.

Phenological and geographical influence in the concentration of selected bioactive 4-phenylcoumarins and chlorogenic acid in Hintonia latiflora leaves

Ethnopharmacological relevanceHintonia latiflora is a Mexican medicinal plant with well-documented ethnomedical record comprising more than 400 years; in modern Mexico is used for treating several maladies such as diabetes and gastric ulcers. Although the pharmacological actions of the stem-bark and leaves have been demonstrated, the phenological and geographical effect on the concentration of active principles remains unexplored. Aim of the studyThe main goals of this study were to analyze the amount of selected 4-phenylcoumarins and chlorogenic acid in the leaves in order to assess the best harvesting period, and consequently their pharmacological efficacy. In addition, the preclinical antidiabetic efficacy of the infusion of the leaves was corroborated using standard pharmacological tests. Materials and methodsThe aqueous extracts from the leaves of Hintonia latiflora were prepared by infusion. For phenological and geographical comparison, leaves of Hintonia latiflora were collected in two different regions in Chihuahua and Michoacán. The material was analyzed by UPLC applying an analytical method that developed and validated for this purpose following the ICH guidelines. Investigation of the antidiabetic action was accomplished using an acute hypoglycemic test and oral glucose and sucrose tolerance tests. ResultsThe validated analytical method was successfully applied for quantifying chlorogenic acid (1) and 4-phenylcoumarins (2–5) in the leaves of 12 different batches (1–12) during one-year period, and seven different batches for each geographical region; the concentration of the metabolites at the phenological cycle was significantly different, their concentration increased during the pre-senescence phase whereas in the leaf renovation stage the highest concentration of 2–5 was reached. The overall analysis of the active compounds concentration between the two populations investigated seems to be less important than the phenological variations. The aqueous extract of the leaves of Hintonia latiflora exerted its antidiabetic effect by different mechanisms showing comparable effect to the organic extract. ConclusionsThe findings of the present investigation reveal that the best harvest season for the leaves of Hintonia latiflora is between the leaves renovation and senescence stages avoiding the flowering period. In addition, no significant differences were found among the two different geographical populations analyzed. The infusions of the leaves, rich in 4-phenylcoumarins and chlorogenic acid, showed comparable antidiabetic action than the organic extract.

Development of a UHPLC-PDA Method for the Simultaneous Quantification of 4-Phenylcoumarins and Chlorogenic Acid in Exostema caribaeum Stem Bark

Potential toxic effects in mice of an infusion prepared from the stem bark of Exostema caribaeum was assessed by means of the Lorke procedure. The preparation was not found to be toxic, with the LD50 value estimated to be more than 5 g/kg. This preparation at 100, 300, and 500 mg/kg also caused a significant hypoglycemic effect and a reduction in the postprandial glycemia peak in both normal and nicotinamide/streptozotocin (NA/STZ)-diabetic mice in an oral sucrose tolerance test. Phytochemical analysis of the infusion revealed that the major active principles are 4-phenylcoumarins (2-8) and chlorogenic acid (1). During this process, a new 4-phenylcoumarin was isolated along with several known analogues. The structure of the new compound was established as 5-O-[β-D-xylopyranosyl-(1→6)-β-D-glucopyranosyl]-7,3',4'-trihydroxy-4-phenylcoumarin (2) by spectroscopic means. A simple, efficient, fast, and reliable UHPLC-PDA analytical method for quantifying 4-phenylcoumarins and chlorogenic acid (1) was developed and validated. Parameters assessed for the method validation were selectivity, linearity, the limits of detection (LOD) and quantification (LOQ), precision, and accuracy. It was found that all calibration curves showed good linearity (R(2) > 0.9931), within the range of concentrations tested.

Antidiabetic Properties of Exostema caribaeum Stem Bark Aqueous Extract

The infusion of the stem-bark of Exostema caribaeum (ECSB) is widely used to treat malaria fevers and diabetes. Herein, we report the preclinical toxicity and efficacy as antidiabetic agent of this widely used preparation. According to the Lorke criteria, the infusion was not toxic to mice since the LD50 was higher than 5000 mg/kg. The aqueous extract of E. caribaeum (ECSB; 500 mg/kg) caused a significant hypoglycemic effect in NA/STZ-diabetic mice (-41.4%) in a classical nine hours experiment, showing an action similar to glibenclamide (positive control). In the oral sucrose tolerance test, ECSB (100, 300 and 500 mg/kg) caused significant decrease of the postprandial peak in both normal and NA/STZ-diabetic mice; the maximum antihyperglycemic effect was observed at the dose of 100 mg/kg (62% of postprandial peak reduction), similar to the activity provoked by acarbose (positive control). The antihyperglycemic and hypoglycemic actions demonstrated for ECSB are due to the presence of 4-phenylcoumarins.

Bioactive Constituents from Hydrangea seemannii and Identification in the Fingerprint of the Infusion Development by UPLC-PDA

Hydrangea seemannii L. Riley (Hydrangeaceae) is used in Mexican traditional medicine for the treatment type II diabetes mellitus. An aqueous extract from the aerial parts of the plant, orally administered to normal and diabetic mice, showed significant hypoglycemic effect. The extract attenuated postprandial hyperglycemia in diabetic mice during oral glucose and sucrose tolerance tests. These results demonstrated that H. seemannii is effective for controlling fasting and postprandial blood glucose levels in animal models. Phytochemical investigation of the active extract led to the isolation of quercetin (1), kaempferol (2), isoquercetin (3), astragalin (4), quercetin 3-O-β-L-arabinopyranoside (5), rutin (6), nicotiflorin (7), chlorogenic acid (8), 3,4-di-O-caffeoylquinic acid (9) and 3,5-di-O-caffeoylquinic acid (10). Most of the isolated compounds have demonstrated significant hypoglycemic or antihyperglycemic effects; therefore, they are the active principles of the plant.

Thielavins A, J and K: α-Glucosidase inhibitors from MEXU 27095, an endophytic fungus from Hintonia latiflora

Bioassay-guided fractionation of the bio-active organic extract obtained from solid-media culture of MEXU 27095, an endophytic fungus isolated from the Mexican medicinal plant Hintonia latiflora (Rubiaceae), led to separation of three tridepsides which were identified as thielavins A, J and K. All three compounds inhibited Saccharomyces cerevisieae α-glucosidase (αGHY) in a concentration-dependent manner with IC50 values of 23.8, 15.8, and 22.1μM, respectively. Their inhibitory action was higher than that of acarbose (IC50=545μM), used as a positive control. Kinetic analysis established that the three compounds acted as non-competitive inhibitors with ki values of 27.8, 66.2 and 55.4μM, respectively (α=1.0, 1.2, 0.7, respectively); acarbose behaved as competitive inhibitor with a ki value of 156.1μM. Thielavin J inhibited the activity of α-glucosidase from Bacillus stearothermophilus (αGHBs) with an IC50 of 30.5μM, being less active than acarbose (IC50=0. 015μM); in this case, compound (2) (ki=20.0μM and α=2.9) and acarbose (ki=0.008μM and α=1.9) behaved as non-competitive inhibitors. Docking analysis predicted that all three thielavins and acarbose bind to homologated αGHBs and to αGHY (PDB: 3A4A) in a pocket close to the catalytic site for maltose and isomaltose, respectively. The α-glucosidase inhibitory properties of thielavin K (3) were corroborated in vivo since it induced a noted antihyperglycemic action during an oral sucrose tolerance test (3.1, 10.0 and 31.6mg/kg) in normal and nicotinamide-streptozotocin diabetic mice. In addition, at a dose of 10mg/kg, it provoked a moderate hypoglycemic activity in diabetic mice.

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

Ethnopharmacological relevanceScutellaria–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 studyTo 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 methodsSC 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 33d, 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. ResultsAfter 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. ConclusionsAccording 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.

In vivo antidiabetic activity and in silico studies on adenosine monophosphate-activated protein kinase (AMPK) of (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone

Effect of bischalcone derivative (2E,5E)-2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone (CA) on blood glucose level and lipid profile was investigated in normoglycemic and streptozotocin (STZ)-induced diabetic rats. In oral glucose and sucrose tolerance test, treatment with CA (25 mg/kg) and glidenclamide (10 mg/kg) significantly improved the glucose and sucrose tolerance in normal animals. In addition, respective treatment for 7-day resulted in significant percentage reduction in serum glucose (SG). In standardized STZ-induced diabetic rats, a single dose of CA treatment exhibited reduction in SG levels at different time intervals compared to basal levels. The lipid profile levels are restored to near-normal value of all tested parameters. The compound CA was docked into the active site of 5′-AMP (adenosine monophosphate)-activated protein kinase (PDB ID: 2OOX). The binding and docking energy were found to be −6.9 and −45.1 kcal/mol, respectively.

Anti-hyperglycemic effects and mechanism of traditional Chinese medicine Huanglian Wan in streptozocin-induced diabetic rats

Ethnopharmacological relevanceHuanglian Wan (HLW) is a prescription of traditional Chinese medicine (TCM), 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 HLW in the treatment of diabetes mellitus. Materials and methodsHLW extract was prepared and the main components (namely berberine and catalpol) 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 low or high dose of HLW extract, acarbose and vehicle for 33 days, respectively. Body weight, food intake, urine volume, urine sugars, fasting plasma glucose and fasting plasma insulin were monitored to evaluate its antidiabetic effects in 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 effect of HLW extract on the maltase and sucrase in vitro was evaluated. ResultsAfter the treatment of HLW extract, 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 HLW extract could lower the postprandial plasma glucose level of diabetic rats. Furthermore, HLW extract could inhibit the activities of sucrase and maltase in vitro. ConclusionsAccording to our present findings, the TCM prescription HLW possessed potent anti-hyperglycemic effect on STZ-induced diabetic rats. And HLW extract 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 streptozotocin.