Oral 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.

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.

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.

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.

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.

Antihyperglycemic activity of the leaves from annona diversifolia Safford. and farnesol on normal and alloxan-induced diabetic mice*

Background: Diabetes mellitus (DM) is a chronic disease characterized by high blood glucose levels resulting from insulin resistance or inadequate insulin secretion. In the world, DM is one of the most frequent non-contagious diseases that affect more than 371 million people. Objective: This study aimed to evaluate the antihyperglycemic properties of the ethanol extract, subsequent fractions, and farnesol obtained from the leaves of Annona diversifolia on alloxan-induced diabetic and normal mice. Materials and Methods: Bioassay-guided fractionation of the ethanol extract of the leaves of A. diversifolia (EELAd) was performed on alloxan-induced Type 2 diabetic and normoglycemic (NM) mice. Oral glucose tolerance test (OGTT), oral sucrose tolerance test (OSTT), and oral lactose tolerance test (OLTT) were performed in fast NM mice (FNM). Results: The EELAd, CHCl3 fraction, and farnesol induced a significant reduction of postprandial hyperglycemia in acute and subchronic tests using AITD mice. When EELAd, CHCl3 fraction, and farnesol were tested on NM in subchronic assays, these did not affect glycemic levels. In the case of acute test on NM, only CHCl3 fraction induced a hypoglycemic effect at 2 h after the treatment. OLTT and OSTT showed that the EELAd, CHCl3 fraction, and farnesol induced a significant reduction of hyperglycemia levels in FNM at 2 h after a lactose or sucrose load comparable to acarbose. In the case of OGTT was observed a significant reduction of hyperglycemia levels in FNM mice at 2 h after a glucose load comparable to canagliflozin. Conclusion: The EELAd and farnesol induced a significant reduction of postprandial hyperglycemia on AITD mice in acute and subchronic assays. Our results suggest that the control of postprandial hyperglycemia may be mediated by the regulation of absorption of glucose and inhibition of disaccharide digestion such as sucrose and lactose. Finally, the results explained the use of A. diversifolia in Mexican traditional medicine as an antihyperglycemic agent.

In vitro and in vivo studies on the alpha-glucosidase inhibitory effects of the leaf extract of Carica papaya Linn

The search for novel alpha-glucosidase inhibitory agents is currently an important scientific endeavour to the biopharmaceutical companies due to their potentials to reduce postprandial hyperglycaemia in type 2 diabetic patients. The present research attempted to investigate the alpha-glucosidase inhibitory effects of the leaf extract of Carica papaya. Aqueous, methanol, ethyl acetate and n-hexane extracts of C. papaya leaf were subjected to in vitro alpha-glucosidase inhibitory studies, and methanol extract was the most potent (IC50 = 171.83 ± 26.89 μg/mL). Consequently, the methanol extract was further fractionated by column chromatography which yielded six pooled fractions (A–F) and fraction A (FA) showed the lowest IC50 (78.62 ± 25.23 μg/mL). Subsequently, the FA was subjected to in vivo oral maltose and sucrose tolerance tests which revealed that FA had potent inhibitory effects on maltose and sucrose tolerance in rats. The computed area under the curves (AUC(0–120)) further indicates that FA (200 mg/kg bw) have better inhibitory activity on maltase than sucrase. The GC-MS analysis of FA indicates the presence of phenolics, various fatty acids and their derivatives. This research suggests that the leaf extract of C. papaya possesses alpha-glucosidase inhibitory effects and might be exploited in retarding postprandial hyperglycaemia.

In Vivo and In Vitro α-Glucosidase Inhibitory Activity of Perfoliatin a from Melampodium Perfoliatum

As part of our effort to discover new α-glucosidase inhibitors from natural sources, it was found that an aqueous extract from Melampodium perfoliatum (Cavanilles) Kunth (Asteraceae) inhibited the activity of rat-intestinal α-glucosidases in a concentration dependent manner (IC50= 958 μg/mL). Fractionation of the active extract led to the isolation of perfoliatin A (1), which was active against the mammal α-glucosidases and a recombinant α-glucosidase with maltase-glucoamylase activity obtained from Ruminococcus obeum. Kinetic analysis revealed that the interaction of 1 with R. obeum-α-glucosidase was noncompetitive. The calculated Ki was 0.68 ± 0.034 mM. In vivo testing using an oral sucrose tolerance test, in healthy and hyperglycemic mice, revealed that perfoliatin A (1) reduced significantly the postprandial peak, consistent with its α-glucosidase inhibitory activity. The effect was comparable or better to that of acarbose, a therapeutically used α-glucosidase inhibitor. Altogether, these findings clearly supported the α-glucosidase inhibitory activity of melampolide-type of sesquiterpene lactones.

Evaluation of the anti-hyperglycemic effect and safety of microorganism 1-deoxynojirimycin.

1-Deoxynojirimycin (DNJ) is a potent α-glucosidase inhibitor and thus beneficial for prevention of diabetes. While we have succeeded in obtaining the culture supernatant extract (CSE) rich in DNJ from microorganism source, information regarding its anti-hyperglycemic effect and safety were still limited. Therefore, this study was aimed to evaluate the anti-hyperglycemic effect and safety of microorganism DNJ. Oral sucrose tolerance test was performed, and the result showed that CSE was able to significantly suppress the blood glucose elevation and suggested DNJ as the main active compound. To determine its safety, the absorption and excretion of microorganism DNJ were evaluated using 15N labeling method. Our findings investigated the recovery rate of 15N from DNJ reached 80% up to 48 hours after oral administration, suggesting its rapid excretion, suggesting the safety of DNJ. This study verified the functional properties and safety of DNJ from microorganisms, suggesting its potential use for functional purpose.

α-Glucosidase Inhibitors from Salvia circinata.

A dried infusion prepared from the aerial parts of Salvia circinata did not provoke acute toxicity in mice (LD50 > 5 g/kg). This infusion showed poor hypoglycemic and antihyperglycemic effects (100-570 mg/kg) when tested in normal and hyperglycemic mice using acute and oral glucose tolerance tests, respectively. However, this infusion possessed antihyperglycemic action in vivo during an oral sucrose tolerance test (31.6-316 mg/kg), suggesting the presence of α-glucosidase inhibitors in S.circinata. Fractionation of a nonpolar extract of the aerial parts of the plant yielded a new biflavone (1) and four new neoclerodane diterpenoid glucosides (2-5) along with the known compounds amarisolide (6), pedalitin (7), apigenin-7-O-β-d-glucoside (8), and the flavone 2-(3,4-dimethoxyphenyl)-5,6-dihydroxy-7-methoxy-4H-chromen-4-one (9). Compounds 1 and 6-9 were active against mammalian α-glucosidases; 6 and 7 were also active against a recombinant α-glucosidase from Ruminococcus obeum and reduced significantly the postprandial peak during an oral sucrose tolerance test in healthy mice, consistent with their α-glucosidase inhibitory activity. Molecular docking and dynamic studies revealed that compounds 6 and 7 might bind to α-glucosidases at the catalytic center of the enzyme.

Anti-Hyperglycemic Activity of Major Compounds from Calea ternifolia

Demethylisoencecalin (1) and caleins A (4) and C (5) (3.16–31.6 mg/kg, p.o.), the major components from an infusion of Calea ternifolia controlled postprandial glucose levels during an oral sucrose tolerance test (OSTT, 3 g/kg) in normal and nicotinamide/streptozotocin (NA/STZ, 40/100 mg/kg) hyperglicemic mice. The effects were comparable to those of acarbose (5 mg/kg). During the isolation of 1, 4, and 5, four additional metabolites not previously reported for the plant, were obtained, namely 6-acetyl-5-hydroxy-2-methyl-2-hydroxymethyl-2H-chromene (3), herniarin (6), scoparone (7), and 4′,7-dimethylapigenin (8). In addition, the structure of calein C (5) was confirmed by X-ray analysis. Pharmacological evaluation of the essential oil of the species (31.6–316.2 mg/kg, p.o.) provoked also an important decrement of blood glucose levels during an OSTT. Gas chromatography coupled with mass spectrometry (GC-MS) analysis of the headspace solid phase microextraction (HS-SPME)-adsorbed compounds and active essential oil obtained by hydrodistillation revealed that chromene 1 was the major component (19.92%); sesquiterpenes represented the highest percentage of the essential oil content (55.67%) and included curcumene (7.10%), spathulenol (12.95%) and caryophyllene oxide (13.0%). A suitable High Performance Liquid Chromatography (HPLC) method for quantifying chromenes 1 and 6-hydroxyacetyl-5-hydroxy-2,2-dimethyl-2H-chromene (2) was developed and validated according to standard protocols.