Sucrose Tolerance Test Research Articles

Antidiabetic Activities and GC-MS Analysis of 4-Methoxychalcone

Diabetes mellitus is a chronic metabolic disease that is mainly characterized by hyperglycemia. Chalcones and their derivatives have demonstrated promising pharmacological potential for the treatment of diabetes. The aim of the study was to evaluate antidiabetic activities and analyze 4-methoxychalcone (MPP) using GC-MS. The compound was characterized using mass spectroscopy, nuclear magnetic resonance and headspace with gas chromatography coupled to mass spectrometry (HS-GC-MS). MPP was evaluated via the inhibition of the alpha-glucosidase enzyme, cell viability and antiglycation and hemolytic activities in vitro. The study of the interaction between the bovine serum albumin protein and MPP was investigated via molecular docking. Oral sucrose tolerance and oral glucose tolerance tests were performed in streptozotocin (STZ)-induced diabetic mice. The HS-GC-MS method was able to accurately detect and characterize the compound, and the interaction between MPP and BSA revealed the remarkable affinity for the two main binding sites of BSA. This was confirmed by the in vitro antiglycation test, since MPP showed activity through both oxidative and non-oxidative stress. MPP significantly attenuated the increase in glycemia after glucose loading in STZ-induced diabetic mice. These results confirm that MPP has antihyperglycemic activity and may be an alternative for the treatment of diabetes mellitus.

Phytochemical analysis and antihyperglycemic activity of Castilleja arvensis

Castilleja genus comprises approximately 211 species, some of them exhibiting potential in treating various diseases. Remarkably, despite its abundance, there is a significant lack of scientific studies that explore the chemical composition and/or therapeutic activity of this genus.In this work, the chemical composition of Castilleja arvensis was determined, and its antihyperglycemic activity was evaluated in vivo, in vitro, and ex vivo. Hydroalcoholic extract of C. arvensis (HECa) was obtained from the maceration of aerial parts. HECa was fractionated by liquid–liquid extractions to obtain the CH2Cl2 fraction (DF), EtOAc fraction (EF), n-BuOH fraction (BF) and aqueous residue (AR). The antihyperglycemic activity was determined in vivo through oral glucose and sucrose tolerance tests in normoglycemic CD-1 mice. Ex vivo assays were performed to determine intestinal glucose absorption, muscular glucose uptake and hepatic glucose production. α-glucosidase inhibitory activity was evaluated in vitro. Phytochemical screening was carried out through conventional chromatography techniques. Structure elucidation of the isolated compounds was performed by GC–MS and NMR experiments.HECa, its fractions and AR showed significant antihyperglycemic activity in vivo. According to the in vitro and ex vivo assays, this effect can be attributed to different mechanisms of action, including a delay in intestinal glucose absorption, an improvement in insulin sensitivity, and the regulation of hepatic glucose production. These effects may be due to different metabolites identified in fractions from the HECa, including genkwanin, acacetin, verbascoside and ipolamiide. Thus, current research shows that C. arvensis is an important source of bioactive compounds for the management of glycemia.

Euclea natalensis Suppresses Postprandial Hyperglycemia in Rats via the Inhibition of α-Glucosidase: In vitro, in vivo, and Molecular Docking Studies

Background:: Postprandial hyperglycemia is a key factor in type 2 diabetes, and its management is critical in alleviating the deleterious consequences of diabetes and its associated micro and macrovascular complications. Objective:: The current study aims to determine the effect of Euclea natalensis leaf extracts on α- glucosidase inhibition in vitro and postprandial hyperglycemia in vivo in rats. Methods:: Sequentially extracted leaf extracts of Euclea natalensis were evaluated for their inhibitory effects on α-glucosidase in vitro and the suppression of postprandial hyperglycemia in normoglycemic rats. The extracts were fingerprinted using a Fourier-transform infrared spectrophotometer (FTIR), and the bioactive compounds were evaluated by molecular docking for their interaction with α-glucosidase. Results:: FTIR fingerprinting of the extracts showed that they contain functional groups of important bioactive phytochemicals. The extracts inhibited α-glucosidase in vitro, with the methanol extract (1 mg/mL) showing the highest inhibitory effect of 93.52 ± 1.50% compared to 69.62% ± 1.45 of the standard drug acarbose (0.05 mg/mL). The extracts also reduced postprandial hyperglycemia in rats in a sucrose tolerance test, where the hexane and methanol extracts performed similarly to Acarbose. Molecular docking studies showed that 20(29)-lupene-3β- isoferulate 3 is the most potent α-glucosidase inhibitor with the lowest binding energy of -10.79 kcal/mol, 2 hydrogen bonds with residues ASP1526 and ASP1157, and numerous Van der Waal interactions with amino acids in the binding pocket of α-glucosidase. Conclusion:: Euclea natalensis leaf extracts were found to suppress postprandial hyperglycemia by inhibiting α-glucosidase activity; thus, it has a promising potential for use as an antidiabetic agent.

High-throughput screening and investigation of the inhibitory mechanism of α-glucosidase inhibitors in teas using an affinity selection-mass spectrometry method.

An affinity selection-mass spectrometry method was applied for high-throughput screening of α-glucosidase (AGH) inhibitors from teas. Fourteen out of nineteen screened AGH inhibitor candidates were clustered as galloylated polyphenols (GPs). "AGH-GPs" interaction studies, including enzyme kinetics, fluorescence spectroscopy, circular dichroism, and molecular docking, jointly suggested that GPs noncompetitively inhibit AGH activity by interacting with amino acid residues near the active site of AGH and inducing changes in AGH secondary structure. Representative GPs and white tea extract (WTE) showed comparable AGH inhibition effects in Caco2 cells and postprandial hypoglycemic efficacy in diabetic mice as acarbose. The area under the curve of oral sucrose tolerance test was lower by 8.16%, 6.17%, and 7.37% than control group in 15mg/kg EGCG, 15mg/kg strictinin, and 150mg/kg WTE group, respectively. Our study presents a high-efficiency approach to discover novel AGH inhibitors and elucidates a potential mechanism by which tea decreases diabetes risks.

Annona cherimola Miller and Its Flavonoids, an Important Source of Products for the Treatment of Diabetes Mellitus: In Vivo and In Silico Evaluations.

The antihyperglycemic activity of ethanolic extract from Annona cherimola Miller (EEAch) and its products were evaluated using in vivo and in silico assays. An α-glucosidase inhibition was evaluated with oral sucrose tolerance tests (OSTT) and molecular docking studies using acarbose as the control. SGLT1 inhibition was evaluated with an oral glucose tolerance test (OGTT) and molecular docking studies using canagliflozin as the control. Among all products tested, EEAc, the aqueous residual fraction (AcRFr), rutin, and myricetin reduced the hyperglycemia in DM2 mice. During the carbohydrate tolerance tests, all the treatments reduced the postprandial peak such as the control drugs. In the molecular docking studies, rutin showed more affinity in inhibiting α-glucosidase enzymes and myricetin in inhibiting the SGLT1 cotransporter, showing ∆G values of -6.03 and -3.32 kcal/mol-1, respectively, in α-glucosidase enzymes. In the case of the SGLT1 cotransporter, molecular docking showed ∆G values of 22.82 and -7.89 in rutin and myricetin, respectively. This research sorts in vivo and in silico pharmacological studies regarding the use of A. cherimola leaves as a source for the development of new potential antidiabetic agents for T2D control, such as flavonoids rutin and myricetin.

Hypoglycemic effect of Nitraria tangutorum fruit by inhibiting glycosidase and regulating IRS1/PI3K/AKT signalling pathway and its active ingredient identification by UPLC-MS.

The hypoglycemic effect of NTB-40 (40% ethanol fraction of Nitraria tangutorum fruit) in type I/II diabetic mice and its underlying mechanism and active ingredient structure were investigated. The postprandial blood glucose (PBG) lowering effect of NTB-40 treatment was confirmed by maltose, starch, and sucrose tolerance tests in alloxan-induced DM mice and sucrase and maltase inhibitory activities in vitro. More importantly, long-term dosing experiments in high-fat diet-STZ-induced diabetic mice further demonstrated that NTB-40 intervention could improve glycolipid metabolism disorder and insulin resistance (IR) by maintaining glucose homeostasis (FBG, OGTT, ITT, FINS, and HOMA-IR) and lipid homeostasis (TC, TG, HDL-C, LDL-C, and FFA), reducing inflammation (IL-6, IL-1β, and TNF-α) and oxidative stress (SOD and MDA), ameliorating the liver's histological structural abnormalities, and modulating the IRS1/PI3K/AKT signaling pathway and downstream targets (FOXO1, GSK3β, GLUT4) for decreasing hepatic gluconeogenesis and promoting glycogen synthesis and glucose uptake. All these results indicated that NTB-40 had an anti-diabetic effect by modulating the IRS1/PI3K/AKT signaling pathway and inhibiting α-glucosidase activity. Finally, the main chemical components of NTB-40, including phenolic acids, flavonoids, and alkaloids, were assigned by UPLC-Triple-TOF MS/MS.

Enhancement of nutraceutical and anti-diabetic potential of fenugreek (Trigonella foenum-graecum). Sprouts with natural elicitors

Trigonella foenum-graecum has been extensively used for centuries in traditional medicine systems for the cure of health ailments including diabetes. Improving the medicinal attributes ofplants through the elicitation strategy is gaining great interest in the recent past. In the current study, an attempt is made to reveal the role and possible mechanism of action of vitamin C elicit phytochemical-rich aqueous extract of 4th day germinated IM6 genotype fenugreek sprouts in the form of lyophilized powder (IM6E) under both in vitro and in vivo conditions. The IM6E demonstrated strong α-glucosidase activity (95.24 %) and moderate α-amylase and invertase inhibition activities under in vitro conditions. The High Performance Thin Layer Chromatography (HPTLC) based analysis demonstrated that IM6E possess significantly higher concentration of phenolic phytochemical quercetin (0.148 %) as compared to diosgenin and trigonelline bioactive anti-diabetic nutraceuticals. In normal rats after loading with glucose and sucrose, the IM6E administration in a dose-dependent manner significantly reduced the post-prandial hyperglycemia, in a similar fashion as the anti-diabetic drug voglibose as evident from the area under curves (AUC) of oral glucose tolerance test (OGTT) and oral sucrose tolerance test (OSTT) tests. The administration of IM6E in streptozotocin (STZ) induced diabetic rats drastically improved the antioxidant activity of plasma in them as determined by Ferric Reducing Ability of Plasma (FRAP) and the effect was found to be dose-dependent. The oral administration of IM6E in diabetic rats normalized almost all the deregulated biochemical markers like liver enzymes, lipids and significantly decreased higher blood glucose levels with increasing insulin levels as compared to diabetic control. The best concentration of IM6E was found to be 300 mg/kg b.w after 21 days of experimentation. The intra-peritoneal glucose tolerance test (IPGTT) in diabetic rats responded very well to IM6E treatment and 100 mg/kg.b.w. behaved almost like the administration of 0.5U insulin/kg bw, and thus indicating the insulinotropic nature of IM6E. Our findings clearly reveal the use of IM6E for diabetes management and at the same it possesses great potential when combined with voglibose to ameliorate diabetes and its associated complications to a greater extent due to synergistic effects as compared to monotherapy. However, more clinical trials need to be performed before recommending IM6E as an anti-diabetic alternative medicine.

Bioreactor-grown exo- and endo-β-glucan from Malaysian Ganoderma lucidum: An in vitro and in vivo study for potential antidiabetic treatment.

This study aims to identify the roles of exo-β-glucan (EPS-BG) and endo-β-glucan (ENS-BG) extracted from Ganoderma lucidum (GL) in inhibiting the alpha-glucosidase enzyme, a target mechanism for postprandial hyperglycaemia regulation. Upscale production of GL was carried out using a 10 L bioreactor. The zebrafish embryo toxicity test (ZFET) was carried out based on OECD guidelines. The hatching rate, survival rate, heart rate, morphological malformation, and teratogenic defects were observed and determined every 24 h from 0–120 h of post-exposure (hpe). For diabetes induction, adult zebrafish (3–4 months of age) were overfed and induced with three doses of 350 mg/kg streptozotocin (STZ) by intraperitoneal injection (IP) on three different days (days 1, 3, and 5). The oral sucrose tolerance test (OSTT) and anti-diabetic activity of EPS-BG and ENS-BG were evaluated (day 7) using the developed model (n = 15). This study showed that EPS is the most potent compound with the highest inhibitory effect toward the alpha-glucosidase enzyme with an IC50 value of 0.1575 mg/ml compared to ENS extracts (IC50 = 0.3479 mg/ml). Both EPS-BG and ENS-BG demonstrated a strong inhibition of alpha-glucosidase activity similar to the clinically approved alpha-glucosidase inhibitor, acarbose (IC50 = 0.8107 mg/ml). ENS-BG is non-toxic toward zebrafish embryos with LC50 of 0.92 mg/ml and showed no significant changes in ZE hatching and normal heart rate as compared to untreated embryos (161 beats/min). Teratogenic effects of ENS-BG (<1.0 mg/ml) on zebrafish embryonic development were not observed. The DM model of zebrafish was acquired after the third dose of STZ with a fasting BGL of 8.98 ± 0.28 mmol/L compared to the normal healthy group (4.23 ± 0.62 mmol/L). The BGL of DM zebrafish after 30 min treated with EPS-BG and ENS-BG showed a significant reduction (p < 0.0001). Both EPS-BG and ENS-BG significantly reduced DM zebrafish’s peak blood glucose and the area under the curve (AUC) in OSTT. Hence, EPS-BG and ENS-BG extracted from GL showed promising inhibition of the alpha-glucosidase enzyme and are considered non-toxic in ZE. Moreover, EPS-BG and ENS-BG reduced blood glucose levels and inhibited hyperglycemia in DM zebrafish.

Antidiabetic Effect of &lt;i&gt;Beta vulgaris&lt;/i&gt; Mixture: Regulation of Glycolytic Enzymes and Pancreatic Beta Cells

Diabetes is a chronic metabolic disease with a high prevalence worldwide. Beet (Beta vulgaris) is a plant that is widely used in many countries and has various biological activities. In this study, we aimed to evaluate the antidiabetic effect of a B. vulgaris mixture (BM). In the in vitro evaluation, we measured the inhibitory activities of α-amylase and α-glucosidase, performed the oral starch tolerance test (OATT) and oral sucrose tolerance test (OSTT) in Sprague Dawley (SD) rats, and evaluated the clinical symptoms, oral glucose tolerance test (OGTT), number of blood cells, and insulin resistance in db/db mice. BM showed an inhibitory effect against α-amylase and α-glucosidase activity and decreased the blood glucose increased in the OATT and OSTT. In the diabetes mouse model, BM alleviated the general symptoms of diabetes and OGTT results showed a decrease in the increased blood sugar level. Regarding diabetes-related tissue weight, BM decreased the reduced pancreatic weight and showed an effect on diabetes-related factors of blood. Histological analysis indicated that BM decreased insulin concentration, insulin resistance, and insulin secretion ability in serum, and increased insulin concentration in the islets of Langerhans. These results demonstrate that BM has an antidiabetic effect through the regulation of glycolytic enzymes and β cell activity in the pancreas.

Oral Administration of Lactobacillus casei and Bifidobacterium bifidum Improves Glucagon like Peptide-1(GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP) Level in Streptozotocin Induced Diabetic Rats

The gut microbiome plays significant role in the function and integrity of the gastrointestinal tract. They also maintain immune homeostasis and host energy metabolism. The metabolic products of these intestinal microbes can alter carbohydrate metabolism, nutrient absorption and reduce appetite to promote healthy lifestyle. Intestinal disbiosis observed in metabolic disorders like obesity and diabetes. Restoration of dysbiosed gut microbiome through oral administration of probiotics that may have profound health effect in diabetes. In case of diabetes, reports postulated impaired level of incretin, therefore we explored the effect of oral administration of probiotic bacteria Lactobacillus casei NCDC 017 (LC017) and Bifidobacterium bifidum NCDC 231 (BB231) alone and in combination on secretion of incretin hormones such as glucagon like peptide-1 and glucose dependent insulinotropic polypeptide. Thirty six male Wistar rats were randomly divided into six groups and diabetes was induced by single dose of streptozotocin (50 mg/kg body weight) in experimental rats intraperitonially except a group of healthy rats. The diabetic rats were daily administered orally with single dose (~107cfu/ml) of LC017 and BB231 alone and in combination for 28 days. Also, one group of diabetic rats was treated with an anti-diabetic drug, acarbose (10mg/kg body weight) and used a standard control. The change in body weight, sucrose tolerance test, GLP-1, GIP level in serum and GLP-1 level in different part of intestine were observed. The results have shown reduction in body weight in diabetic rats as compared to non-diabetic rats but improved after treatment of probiotic bacteria. Administration of LC017 and BB231 significantly improved GLP-1 and GIP level which were initially impaired in diabetic rats and their combination significantly decreased glucose level in sucrose tolerance test. This study indicated that LC017 and BB231 have significant hypoglycaemic potential in diabetic rats by increasing GLP-1 and GIP level. These findings offered a base for the use of LC017 and BB231 for improvement and treatment of diabetes.

α-Glucosidase and PTP-1B Inhibitors from Malbranchea dendritica.

An extract from a PDB static culture of Malbranchea dendritica exhibited α-glucosidase and PTP-1B inhibitory activities. Fractionation of the active extract led to the isolation of gymnoascolide A (1), a γ-butenolide, and xanthones sydowinin A (2), sydowinin B (3), and AGI-B4 (4), as well as orcinol (5). Compound 1 exhibited important inhibitory activity against yeast α-glucosidase (IC50 = 0.556 ± 0.009 mM) in comparison to acarbose (IC50 = 0.403 ± 0.010 mM). Kinetic analysis revealed that 1 is a mixed-type inhibitor. Furthermore, compound 1 significantly reduced the postprandial peak in mice during a sucrose tolerance test at the doses of 5.16 and 10 mg/kg. Compound 1 was reduced with Pd/C to yield a mixture of enantiomers 1a and 1b; the mixture showed similar activity against α-glucosidase (IC50 = 0.396 ± 0.003 mM) and kinetic behavior as the parent compound but might possess better drug-likeness properties according to SwissADME and Osiris Property Explorer tools. Docking analysis with yeast α-glucosidase (pdb: 3A4A) and the C-terminal subunit of human maltase-glucoamylase (pdb: 3TOP) predicted that 1, 1a, and 1b bind to an allosteric site of the enzymes. Compounds 1–5 were evaluated against PTP-1B, but only xanthone 3 moderately inhibited in a noncompetitive fashion the enzyme with an IC50 of 0.081 ± 0.004 mM. This result was consistent with that of docking analysis, which revealed that 3 might bind to an allosteric site of the enzyme. From the inactive barley-based semisolid culture of M. dendritica, the natural pigment erythroglaucin (6) and the nucleosides deoxyadenosine (7), adenosine (8), thymidine (9), and uridine (10) were also isolated and identified.

Effects of endurance exercise on serum inflammatory cytokine level and kidney structure in a rat diabetes model

Diabete mellitus (DM) is becoming a global health problem. Whilst many studies have previously focused on the therapeutic effects of exercise on diabetes, insufficient data exist on its effectiveness on disease prevention. The present study was designed to evaluate the effects of endurance exercises on kidney injury and on the expression of metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor (TGF)-β1. Type 2 diabetic rat model was created followng 8 weeks of feeding on high fat diet, followed by injection with streptozotocin (STZ; 30 mg/kg). A total of three different intensity endurance exercises, including low-intensity exercise (8 m/min and 0˚ slope), moderate-intensity exercise (15 m/min and 5˚ slope) and high-intensity exercise (20 m/min and 10˚ slope), were arranged during this process. Oral glucose tolerance (OGTT) and oral sucrose tolerance tests (OSTT) were performed in all rats 1 week after STZ injection. Serum interleukin-6 and tumor necrosis factor-α levels were measured using ELISA. After OGTT, all rats were sacrificed and kidney samples were removed for hematoxylin and eosin staining and western blot analyzes. Urea and ureatinine levels, representative of renal function, were estimated by using automatic biochemical analyzer. Rats in the DM group showed severe impaired glucose tolerance, which was alleviated in the moderate-intensity exercise (ME) and the high-intensity exercise (HE) groups. Inflammatory cytokines were also significantly reduced rats in the ME group compared with those in the DM group. No difference in renal function, MMP-9/TIMP-1 and TGF-β1 expression was observed. In addition, rats in the DM group exhibited glomerular enlargement with structural renal abnormalities, whilst those in the ME and HE groups showed improved symptoms. To conclude, no increased expression of inflammatory cytokines and renal fibrotic proteins could be observed in the present rat model of type-2 DM, but evident structural abnormalities can be observed in the kidneys. Medium-intensity endurance exercise can reduce serum inflammatory cytokine levels and prevent aberrant changes in renal structures.

Antihyperglycemic Activities of Uli Banana Leaves on Oral Sugar Tolerance

Banana has been widely cultivated. This study aimed to determine the antihyperglycemic activity of Uli banana leaves infusion. The antihyperglycemic activity was evaluated by oral glucose and sucrose tolerance test. A bolus of sugar was given after Uli banana leaves infusion and blood was sampled at 0, 15, 30, 60, 90 and 120 minutes for glucose analyses. The trapezoidal rule was used to determine the area under the curve (AUC) blood glucose. Infusion of Uli banana leaves 3.3 g/kg showed a significant decrease AUC (p&lt;0.05) in the glucose tolerance test, while that of dose 0.8 g/kg reduced significantly (p&lt;0.05) in the sucrose tolerance test. The results showed that Uli banana leaves infusion possesses antihyperglycemic effect in mice.

α-Glucosidase and Protein Tyrosine Phosphatase 1B Inhibitors from Malbranchea circinata.

During a search for new α-glucosidase and protein tyrosine phosphatase 1B inhibitors from fungal sources, eight new secondary metabolites, including two anthranilic acid-derived peptides (1 and 2), four glycosylated anthraquinones (3-6), 4-isoprenylravenelin (7), and a dimer of 5,8-dihydroxy-4-methoxy-α-tetralone (8), along with four known compounds (9-12), were isolated from solid rice-based cultures of Malbranchea circinata. The structural elucidation of these metabolites was performed using 1D and 2D NMR techniques and DFT-calculated chemical shifts. Compounds 1-3, 9, and 10 showed inhibitory activity to yeast α-glucosidase (αGHY), with IC50 values ranging from 57.4 to 261.3 μM (IC50 acarbose = 585.8 μM). The effect of 10 (10.0 mg/kg) was corroborated in vivo using a sucrose tolerance test in normoglucemic mice. The most active compounds against PTP-1B were 8-10, with IC50 values from 10.9 to 15.3 μM (IC50 ursolic acid = 27.8 μM). Docking analysis of the active compounds into the crystal structures of αGHY and PTP-1B predicted that all compounds bind to the catalytic domains of the enzymes. Together, these results showed that M. circinata is a potential source of antidiabetic drug leads.

Antioxidant Properties and Digestive Enzyme Inhibitory Activity of the Aqueous Extract from Leafy Stems of Cissus polyantha.

Cissus polyantha (Vitaceae) is a plant used in Cameroonian traditional medicine for the treatment of diabetes. The aims of this study were to evaluate the in vitro antioxidant and antidiabetic activities of the aqueous extract of Cissus polyantha leafy stems. The enzyme inhibitory activity was determined in vitro on α-amylase and α-glucosidase enzymes, followed by confirmative study in vivo on normal rats (oral starch and sucrose tolerance tests at doses of 111, 222, and 444 mg/kg). The ferric reducing antioxidant power and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) antiradical activity of the extract were examined to evaluate the antioxidant potential of the extract. The total content of phenols, flavonoids, and tannins of the extract were also determined. The results showed an inhibitory effect of the extract on the α-amylase and α-glucosidase activities with IC50 values of 216.14 and 182.40 μg/mL, respectively. The extract at doses of 222 and 444 mg/kg induced a significant decrease in postprandial glycaemia during the starch and sucrose tolerance tests. A remarkable antiradical activity of the extract was obtained although lower than that of the standard product. The aqueous extract of leafy stems of Cissus polyantha has an interesting inhibitory activity on the α-amylase and α-glucosidase enzymes, as well as an antioxidant potential, thus validating its use in traditional medicine for the treatment of diabetes mellitus and its complications.

Chitosan oligosaccharide (GO2KA1) improves postprandial glycemic response in subjects with impaired glucose tolerance and impaired fasting glucose and in healthy subjects: a crossover, randomized controlled trial

BackgroundThe antidiabetic and hypoglycemic effects of chitosan have been reported in previous studies. We have previously shown that chitosan oligosaccharide reduces postprandial blood glucose levels in vivo. We conducted a short-term crossover study to support the results of the previous study.MethodsThe study was a randomized, double-blind, controlled crossover trial completed at one clinical research site. Subjects with impaired glucose tolerance and impaired fasting glucose and healthy subjects were randomly assigned to consume one of two different experimental test capsules that differed in only the sample source (GO2KA1 vs placebo), and all subjects were instructed to consume the 75 g sucrose within 15 min. After a 7-day interval, the subjects consumed the other capsules that were not consumed on the first day. We assessed blood glucose levels using a 2-h oral sucrose tolerance test. The study was registered at clinicaltrials.gov (NCT03650023).ResultsThe test group showed significantly lower blood glucose levels at 60 min (p = 0.010) and postprandial blood glucose areas under the curve (p = 0.012). The change in blood glucose levels at 60 min was significantly lower in the test group than in the placebo group (p = 0.017).ConclusionsBased on the results of this study, the consumption of chitosan oligosaccharide (GO2KA1) supplements with a meal can effectively reduce postprandial blood glucose levels, which is relevant to the prevention of diabetes.

Formulation of a Mixture of Plant Extracts for Attenuating Postprandial Glycemia and Diet-Induced Disorders in Rats.

The aim of this study was to design a mixture consisting of plant-derived preparations containing inhibitors of carbohydrate digestion and/or glucose absorption that could lower postprandial glycemia and attenuate dietary-induced disorders. The following standardized preparations were tested: white mulberry leaf extract, green coffee bean extract, white kidney bean extract, pomelo fruit extract, bitter melon fruit extract, and purified l-arabinose. The study design was composed of oral sucrose and starch tolerance tests in Wistar rats preceded by a single ingestion of the preparations or their mixtures. Then, a 20 week-long experiment was conducted on rats that were fed a high-fat diet and supplemented with the most effective mixture. Based on the results of the oral sucrose and starch tolerance tests, the mulberry leaf extract, l-arabinose, kidney bean extract, and coffee bean extract were selected for composing three mixtures. The most effective inhibition of postprandial glycemia in the oral tolerance tests was observed after the ingestion of a mixture of mulberry leaf, kidney bean, and coffee bean extract. The glucose-lowering effect of the mixture and its effective dosage was confirmed in the feeding experiment.

Indirect Chronic Effects of an Oleuropein-Rich Olive Leaf Extract on Sucrase-Isomaltase In Vitro and In Vivo.

Consumption of dietary bioactives is an avenue to enhancing the effective healthiness of diets by attenuating the glycaemic response. The intestinal brush border enzyme sucrase-isomaltase (SI) is the sole enzyme hydrolysing consumed sucrose, and we previously showed the acute effects of olive leaf extract (OLE) on sucrase activity when given together with sugars both in vitro and in vivo. Here we tested whether OLE could affect sucrase expression when pre-incubated chronically, a “priming” effect not dependent on competitive interaction with SI, in both a cell model and a human intervention. Using differentiated Caco-2/TC7 cells, long-term pre-treatment with oleuropein-rich olive leaf extract (OLE) lowered SI mRNA, surface protein and activity, and attenuated subsequent sucrose hydrolysis. Based on these results, a randomised, double-blinded, placebo-controlled, crossover pilot study was conducted. OLE (50 mg oleuropein) was consumed in capsule form 3 times a day for 1 week by 11 healthy young women followed by an oral sucrose tolerance test in the absence of OLE. However this treatment, compared to placebo, did not induce a change in post-prandial blood glucose maximum concentration (Glcmax), time to reach Glcmax and incremental area under the curve. These results indicate that changes in SI mRNA, protein and activity in an intestinal cell model by OLE are not sufficient under these conditions to induce a functional effect in vivo in healthy volunteers.

New olean-15-ene type gymnemic acids from Gymnema sylvestre (Retz.) R.Br. and their antihyperglycemic activity through α-glucosidase inhibition

A mixture of gymnemic acids was precipitated from the water extract of leaves of Gymnema sylvestre (Retz.) R.Br. ex Sm. (Asclepiadaceae) by acidification with 2 N H2SO4. The chromatographic separation of the mixture afforded five new gymnemic acids (1-5). The compounds were characterized as Δ15 oleanane glycosides on the basis of extensive spectral data analysis. The compounds (1-5) showed dose dependent inhibition of α-glucosidase, which was found to be comparable to acarbose (IC50 95 μg/ml). Maximum inhibition was achieved with compound 4 (IC50 57 μg/ml) followed by 3 (IC50 62 μg/ml), 1 (IC50 80 μg/ml), 2 (IC50 120 μg/ml) and 5 (IC50 128 μg/ml). The results revealed that the overall pattern of hydroxyl and acyl substitutions of compounds affected their inhibitory activity. In oral sucrose tolerance test, pre-treatment with crude gymnemic acid mixture and isolated compounds 1 and 4 at a dose of 10 mg/Kg b.w. significantly blunted the effect of sucrose challenge in mice. Based on these results, the antihyperglycemic effect of G. sylvestre can be, at least partly, attributed to the inhibition of α-glucosidase by its gymnemic acids. The current study provides relatively more direct evidence explaining the effectiveness of G. sylvestre against hyperglycemia.

Enterococcus faecalis YM0831 suppresses sucrose-induced hyperglycemia in a silkworm model and in humans

Hyperglycemia caused by excessive intake of sucrose leads to lifestyle-related diseases such as diabetes. Administration of a lactic acid bacterial strain to mice suppresses sucrose-induced hyperglycemia, but evidence for a similar effect in humans is lacking. Here we show that Enterococcus faecalis YM0831, identified using an in vivo screening system with silkworms, suppressed sucrose-induced hyperglycemia in humans. E. faecalis YM0831 also suppressed glucose-induced hyperglycemia in silkworms. E. faecalis YM0831 inhibited glucose uptake by the human intestinal epithelial cell line Caco-2. A transposon insertion mutant of E. faecalis YM0831, which showed decreased inhibitory activity against glucose uptake by Caco-2 cells, also exhibited decreased inhibitory activity against both sucrose-induced and glucose-induced hyperglycemia in silkworms. In human clinical trials, oral ingestion of E. faecalis YM0831 suppressed the increase in blood glucose in a sucrose tolerance test. These findings suggest that E. faecalis YM0831 inhibits intestinal glucose transport and suppresses sucrose-induced hyperglycemia in humans.