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Sample records for acarbose

  1. Acarbose als Carbophor

    Merettig, Nadine

    2014-01-01

    Das Pseudotetrasaccharid Acarbose ist seit 1990 als kompetitiver Inhibitor intestinaler α-Glucosidasen (GlucobayTM/PrecoseTM) in der medizinischen Anwendung bei der Therapie von Diabetes mellitus Typ-2. Charakteristisch für die Struktur der Acarbose ist die Acarviosyleinheit, bei der Valinamin und Desoxyglucose N-glycosidisch verknüpft sind; des Weiteren ist an die Acarviosyleinheit ein Maltosylrest gebunden. Der Inhibitoreffekt beruht auf der irreversiblen Bindung zwischen ...

  2. Acarbose Bioequivalence: Exploration of New Pharmacodynamic Parameters

    Zhang, Min; Yang, Jin; Tao, Lei; Li, Lingjun; Ma, Pengcheng; Fawcett, John Paul

    2012-01-01

    To investigate bioequivalence (BE) testing of an acarbose formulation in healthy Chinese volunteers through the use of recommended and innovative pharmacodynamic (PD) parameters. Following the Food and Drug Administration (FDA) guidance, a randomized, cross-over study of acarbose test (T) and reference (R) (Glucobay®) formulations was performed with a 1-week wash-out period. Preliminary pilot studies showed that the appropriate dose of acarbose was 2 × 50 mg, and the required number of subjec...

  3. Acarbose

    ... help to manage your diabetes and improve your health. This therapy may also decrease your chances of ... lightheadedness sweating nervousness or irritability sudden changes in behavior ... loss of consciousness Call your doctor immediately if you have any ...

  4. Acarbose

    ... Over time, people who have diabetes and high blood sugar can develop serious or life-threatening complications, including ... diet, exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve ...

  5. Compound list: acarbose [Open TG-GATEs

    Full Text Available acarbose ACA 00116 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/in_vitro/acar...bose.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vitro/acar...bose.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver/Single/acar...-tggates/LATEST/Rat/in_vivo/Liver/Repeat/acarbose.Rat.in_vivo.Liver.Repeat.zip ...

  6. Effect of acarbose, pectin, a combination of acarbose with pectin, and placebo on postprandial reactive hypoglycaemia after gastric surgery.

    Speth, P A; Jansen, J.B.; Lamers, C.B.

    1983-01-01

    In a double-blind study we have compared the effect of 50 mg acarbose, 100 mg acarbose, 4.2 g pectin, a combination of 50 mg acarbose with 4.2 g pectin, and placebo on plasma glucose, plasma insulin, breath hydrogen and hypoglycaemic symptoms after a normal carbohydrate rich meal in nine patients with previous gastric surgery. Fifty milligrams acarbose, 100 mg acarbose and the combination of 50 mg acarbose with 4.2 g pectin significantly inhibited the postprandial peak glucose concentration (...

  7. Acarbose bioequivalence: exploration of new pharmacodynamic parameters.

    Zhang, Min; Yang, Jin; Tao, Lei; Li, Lingjun; Ma, Pengcheng; Fawcett, John Paul

    2012-06-01

    To investigate bioequivalence (BE) testing of an acarbose formulation in healthy Chinese volunteers through the use of recommended and innovative pharmacodynamic (PD) parameters. Following the Food and Drug Administration (FDA) guidance, a randomized, cross-over study of acarbose test (T) and reference (R) (Glucobay®) formulations was performed with a 1-week wash-out period. Preliminary pilot studies showed that the appropriate dose of acarbose was 2 × 50 mg, and the required number of subjects was 40. Serum glucose concentrations after sucrose administration (baseline) and co-administration of sucrose/acarbose on the following day were both determined. Three newly defined PD measures of glucose fluctuation (glucose excursion (GE), GE' (glucose excursion without the effect of the homeostatic glucose control), and fAUC (degree of fluctuation of serum glucose based on AUC)), the plateau glucose concentration (C(ss)), and time of maximum reduction in glucose concentration (T (max)) were tested in the evaluation. The adequacy of the two parameters recommended by the FDA, ΔC(SG,max) (maximum reduction in serum glucose concentration) and AUEC((0-4h)) (reduction in the AUC((0-4h)) of glucose between baseline and acarbose formulation) was also evaluated. The T (max) values were comparable, and the 90% confidence intervals of the geometric test/reference ratios (T/R) for ΔC(SG,max), C(ss), GE, and fAUC were all within 80-125%. The parameter GE' was slightly outside the limits, and the parameter AUEC((0-4h)) could not be computed due to the presence of negative values. In acarbose BE evaluation, while the recommended parameter ΔC(SG,max) is valuable, the combination of C(ss) and one of the newly defined glucose fluctuation parameters, GE, GE', and fAUC is preferable than AUEC((0-4h)). The acarbose test formulation can be initially considered to be bioequivalent to Glucobay®. PMID:22419151

  8. Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose.

    Singla, Rajeev Kumar; Singh, Radha; Dubey, Ashok Kumar

    2016-01-01

    Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function. PMID:27086787

  9. Influence of gallic acid on α-amylase and α-glucosidase inhibitory properties of acarbose

    Ganiyu Oboh

    2016-07-01

    Full Text Available Acarbose is an antidiabetic drug which acts by inhibiting α-amylase and α-glucosidase activities but with deleterious side effects. Gallic acid (GA is a phenolic acid that is widespread in plant foods. We therefore investigated the influence of GA on α-amylase and α-glucosidase inhibitory properties of acarbose (in vitro. Aqueous solutions of acarbose and GA were prepared to a final concentration of 25μM each. Thereafter, mixtures of the samples (50% acarbose + 50% GA; 75% acarbose+25% GA; and 25% acarbose+75% GA were prepared. The results revealed that the combination of 50% acarbose and 50% GA showed the highest α-glucosidase inhibitory effect, while 75% acarbose+25% GA showed the highest α-amylase inhibitory effect. Furthermore, all the samples caused the inhibition of Fe2+-induced lipid peroxidation (in vitro in rat pancreatic tissue homogenate, with the combination of 50% acarbose and 50% GA causing the highest inhibition. All the samples also showed antioxidant properties (reducing property, 2,2'-azino-bis (-3-ethylbenzthiazoline-6-sulphonate [ABTS*] and 1,1-diphenyl-2-picrylhydrazyl [DPPH] free radicals scavenging abilities, and Fe2+ chelating ability. Therefore, combinations of GA with acarbose could be employed as antidiabetic therapy, with a possible reduction of side effects of acarbose; nevertheless, the combination of 50% acarbose and 50% GA seems the best.

  10. Application of TLC in the Screening of Acarbose-producing Actinomycetes

    Fei Ren; Long Chen; Qunyi Tong

    2014-01-01

    Acarbose is widely used in medicine, such as the treatment of diabetes and obesity. A simple Thin Layer Chromatography (TLC)-scanning technique was developed for the rapid and accurate analysis of acarbose in a large number of fermentation broths of actinomycetes to screen for acarbose producer. The linearity of the acarbose in this way was good within the range from 2 to 10 μg (r2 = 0.9997). This technique didn’t need expensive instrument and complex procedure for the detection of acarbose i...

  11. Kinetic Determination of Acarbose and Miglitol in Bulk and Pharmaceutical Formulations Using Alkaline Potassium Permanganate

    Ibrahim, F. A.; Ali, F. A.; Ahmed, S. M.; Tolba, M. M.

    2007-01-01

    A simple and sensitive kinetic spectrophotometric method was established for the determination of acarbose and miglitol in bulk and in their pharmaceutical preparations using alkaline potassium permanganate as an oxidizing agent. The method involves determination of acarbose and miglitol by kinetic studies of their oxidation at room temperature for a fixed time of 15 minutes for acarbose and 25 minutes for miglitol. The absorbance of the colored manganate ion was measured at 610 nm. Alternati...

  12. Safety and efficacy of acarbose in the treatment of diabetes in Chinese patients

    He K

    2014-06-01

    Full Text Available Ke He*, Jun-Cheng Shi*, Xiao-Ming Mao Department of Endocrinology, Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing, People's Republic of China *These authors contributed equally to this work Abstract: Acarbose is an α-glucosidase inhibitor that is commonly used to control postprandial blood glucose. It functions as a competitive and reversible inhibitor of small intestinal brush border glucosidase, blocks the degradation of starch and sucrose, and delays the absorption of glucose and fructose in the alimentary tract. The starch content of a diet might alter the hypoglycemic effects of acarbose because of its mechanism of action. Chinese individuals consume a typical Eastern diet, which is characterized by a high intake of whole grains, legumes, vegetables, fruits, and fish. These dietary habits allow acarbose to be used extensively in the People's Republic of China. Several Chinese-based studies have demonstrated that the use of acarbose as a monotherapy had similar effects on other anti-diabetes agents in decreasing glycosylated hemoglobin (HbA1c and blood glucose levels, and acarbose in combination with other anti-diabetic drugs could further reduce blood glucose and decrease the mean amplitude of glycemic excursions. Importantly, acarbose is safe and well tolerated, with a low incidence of adverse effects. This article provides a comprehensive review of the safety and efficacy of acarbose for the treatment of diabetes in Chinese patients. Keywords: acarbose, α-glucosidase inhibitor, efficacy, safety

  13. Cardiovascular benefits and safety profile of acarbose therapy in prediabetes and established type 2 diabetes

    Hanefeld Markolf

    2007-08-01

    Full Text Available Abstract Dysglycaemic disease is one of the most important health issues facing the world in the 21st century. Patients with type 2 diabetes and individuals with prediabetes are at risk of developing macrovascular and microvascular complications. Long-term management strategies are therefore required that are effective at controlling dysglycaemia, well tolerated and, ideally, offer additional cardiovascular disease (CVD risk-reduction benefits. The efficacy, safety and tolerability of the α-glucosidase inhibitor acarbose have been well-established in a wide range of patient populations in both clinical and community trials. In addition, acarbose has been shown to reduce cardiovascular complications in type 2 diabetes and prevent hypertension and CVD in individuals with impaired glucose tolerance (IGT. Acarbose has a very good safety profile and, owing to its straightforward, non-systemic mode of action, avoids most adverse events. The most common side-effects of acarbose are mild-to-moderate gastrointestinal complaints that subside as treatment continues. They can be minimised through the use of an appropriate stepwise dosing regimen and careful choice of diet. Acarbose is therefore a valuable option for the management of type 2 diabetes and, as the only oral antidiabetes agent approved for the treatment of prediabetes, can help to improve clinical management across the dysglycaemic disease continuum.

  14. Kinetic determination of acarbose and miglitol in bulk and pharmaceutical formulations using alkaline potassium permanganate.

    Ibrahim, F A; Ali, F A; Ahmed, S M; Tolba, M M

    2007-03-01

    A simple and sensitive kinetic spectrophotometric method was established for the determination of acarbose and miglitol in bulk and in their pharmaceutical preparations using alkaline potassium permanganate as an oxidizing agent. The method involves determination of acarbose and miglitol by kinetic studies of their oxidation at room temperature for a fixed time of 15 minutes for acarbose and 25 minutes for miglitol. The absorbance of the colored manganate ion was measured at 610 nm. Alternatively, the kinetic decrease in the absorbance of permanganate upon addition of the studied drugs at 525 nm was also used. The absorbance concentration plot was rectilinear over the concentration range of 4-20 and 1-10 μg/ml for acarbose and miglitol, respectively. The detection limits were 0.189 and 0.089 μg/ml at 610 nm and 0.081 and 0.179 μg/ml at 525 nm for acarbose and miglitol respectively. The method was successfully applied for the determination of these drugs in their dosage forms. The results obtained were in good agreement with those obtained with the reference methods. PMID:23675017

  15. Effects of acarbose on fecal nutrients, colonic pH, and short-chain fatty acids and rectal proliferative indices.

    Holt, P R; Atillasoy, E; Lindenbaum, J; Ho, S B; Lupton, J R; McMahon, D; Moss, S F

    1996-09-01

    Acarbose, an alpha-glycosidase inhibitor, treats diabetes mellitus by delaying the digestion and intestinal absorption of dietary carbohydrates. In effective doses, acarbose induces some passage of carbohydrates into the colon. The effect of such chronic carbohydrate transfer on colonic structure and function is unknown. We studied the effects of 1 year of acarbose administration in diabetes mellitus on fecal energy, protein, and fat, including short-chain fatty acids (SCFA) output, fecal pH, and several metabolizing bacterial species. Changes in colonic histology and epithelial cell proliferation were investigated in rectal biopsies. Fecal macronutrient output was unaffected by acarbose, but pH decreased and total SCFA, butyrate, and acetate output were markedly greater. Breath hydrogen output increased after acarbose, but digoxin-metabolizing bacteria and diacylglycerol (DAG) production were unaltered. Compared with the control, acarbose did not induce hyperplasia or change rectal proliferation. However, total fecal SCFA and butyrate output correlated inversely with proliferation in the rectal upper crypt-a biomarker of risk for colonic neoplasia. In conclusion, long-term acarbose administration does not adversely affect colonic function or fecal nutrient output. If increased fecal SCFA and butyrate reduces upper-crypt proliferation, then acarbose may reduce the risk of colonic neoplasia. PMID:8781308

  16. Inhibitory effect and mechanism of acarbose combined with gymnemic acidon maltose absorption in rat intestine

    Hong Luo; Le Feng Wang; Toshiaki Imoto; Yasutaka Hiji

    2000-01-01

    AIM The control of diet regimen and nutrient intake, aiming to avoid the evaggerated levels of glucose andanabolic hormone is broadly accepted as basic treatment of diabetes mellitus. Maltose is an importanthydrolysate of starch, main source of nutrition. Acarbose is an alpha-D-glucosidase inhibitor but with a shortinhibitory duration. Gymnemic acid (GA), a group of triterpene glucuronides, inhibits glucose absorptionwith a longer effective duration but it needs a longer time to achieve its maximum effect. To determinewhether nutrient control in diabetic care can be improved by combination of them, we compared thecombinative and individual effect of acarbose and GA on maltose absorption and hydrolysis in smallintestine.METHODS The absorption and hydrolysis of maltose were studied by re-cyclic perfusion of intestinal loopsin situ and motility of the intestine was recorded with the intestinal loop in vitro, of Wistar rat.RESULTS The total inhibitory rate of maltose absorption was improved by the combination of GA (0.1 -1.0 mg/mL) and acarbose (0.1- 2.0 mmol/L) throughout their effective duration (P<0.05, U test ofMann-Whitney), although the improvement only could be seen in the low dosages during the first hour. Withthe combination, inhibitory duration of acarbose on maltose absorption was prolonged to 3 hours and theonset of GA inhibitory effect was fastened to 15 minutes. GAsuppressed the intestinal mobility with a goodcorrelation (r = 0.98) to the inhibitory effect of GA on maltose absorption and the inhibitory effect of2 mmol/L (higher dose) acarbose on maltose hydrolysis was dual modulated by 1 mg/mL GA in vivoindicating that the combined effects involved the functional alteration of intestinal barriers.CONCLUSION There are augmented effects of acarbose and GA, which involve pre-cellular andparacellular barriers. Furthermore, diabetic care can be improved by employing this combination.

  17. Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters

    Rosenbaum P.

    2002-01-01

    Full Text Available A double-blind, randomized, placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure (BP and hormonal parameters. Before randomization and after a 22-week treatment period (100 to 300 mg/day, the subjects were submitted to a standard meal test and to 24-h ambulatory BP monitoring (ABPM and had plasma glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin levels determined. Weight loss was found only in the acarbose-treated group (75.1 ± 11.6 to 73.1 ± 11.6 kg, P<0.01. Glycosylated hemoglobin decreased only in the acarbose group (6.4 ± 1.7 to 5.6 ± 1.9%, P<0.05. Fasting proinsulin decreased only in the acarbose group (23.4 ± 19.3 to 14.3 ± 13.6 pmol/l, P<0.05, while leptin decreased in both (placebo group: 26.3 ± 6.1 to 23.3 ± 9.4 and acarbose group: 25.0 ± 5.5 to 22.7 ± 7.9 ng/ml, P<0.05. When the subset of acarbose-treated patients who improved glycemic control was considered, significant reductions in diurnal systolic, diastolic and mean BP (102.3 ± 6.0 to 99.0 ± 6.6 mmHg, P<0.05 were found. Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients. Acarbose-induced improvement in metabolic control may reduce BP in these patients. Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels.

  18. Efficacy and safety of acarbose in the treatment of elderly patients with postprandial hypotension

    JIAN Zai-jin; ZHOU Bai-yu

    2008-01-01

    Background Postprandial hypotension (PPH) occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose (a-glucosidase inhibitor), a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment.Methods Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days: screening day and intervention day. Blood pressure and heart rate (HR) were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction (EF) and fractional shortening (FS) were measured by two dimensional echocardiography.Results Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure (SBP, DBP, MAP) (all P<0.05) were significantly attenuated after taking acarbose during breakfast, so were MAP (P<0.05) during lunch, DBP (P<0.05) and MAP (P<0.05) during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction (ADR) was 9%. Conclusion Acarbose is effective and safe in the treatment of elderly patients with PPH.

  19. Reassessment of acarbose as a transition state analogue inhibitor of cyclodextrin glycosyltransferase

    Mosi, Renee; Sham, Howard; Uitdehaag, Joost C.M.; Ruiterkamp, Richard; Dijkstra, Bauke W.; Withers, Stephen G.

    1998-01-01

    The binding of several different active site mutants of Bacillus circulans cyclodextrin,glycosyltransferase to the inhibitor acarbose has been investigated through measurement of Ki values. The mutations represent several key amino acid positions, most of which are believed to play important roles in governing the product specificity of cyclodextrin glycosyltransferase. Michaelis-Menten parameters for the substrates alpha-maltotriosyl fluoride (alpha G3F) and alpha-glucosyl fluoride (alpha GF...

  20. INFLUENCE OF ACARBOSE ON POSTPRANDIAL DYSMETABOLISM: RESULTS OF AN OPEN-LABEL RANDOMIZED STUDY

    A. Ya. Cherniak; I. M. Petrov; I V Medvedeva

    2015-01-01

    Aim. To evaluate postprandial changes of lipid and glucose profiles, inflammation markers levels and flow-mediated vasodilatation in patients with metabolic syndrome (MS) and to estimate acarbose course treatment efficacy in glucose intolerant patients.Material and methods. A total of 114 MS patients (83 men, 31 women) were examined, MS was associated with impaired glucose tolerance (IGT) in 55 cases. At the first stage postpran- dial dynamics of flow-mediated dilation (FMD), lipid profile pa...

  1. Acarbose, lente carbohydrate, and prebiotics promote metabolic health and longevity by stimulating intestinal production of GLP-1.

    McCarty, Mark F; DiNicolantonio, James J

    2015-01-01

    The α-glucosidase inhibitor acarbose, which slows carbohydrate digestion and blunts postprandial rises in plasma glucose, has long been used to treat patients with type 2 diabetes or glucose intolerance. Like metformin, acarbose tends to aid weight control, postpone onset of diabetes and decrease risk for cardiovascular events. Acarbose treatment can favourably affect blood pressure, serum lipids, platelet aggregation, progression of carotid intima-media thickness and postprandial endothelial dysfunction. In mice, lifetime acarbose feeding can increase median and maximal lifespan-an effect associated with increased plasma levels of fibroblast growth factor 21 (FGF21) and decreased levels of insulin-like growth factor-I (IGF-I). There is growing reason to suspect that an upregulation of fasting and postprandial production of glucagon-like peptide-1 (GLP-1)-stemming from increased delivery of carbohydrate to L cells in the distal intestinal tract-is largely responsible for the versatile health protection conferred by acarbose. Indeed, GLP-1 exerts protective effects on vascular endothelium, the liver, the heart, pancreatic β cells, and the brain which can rationalise many of the benefits reported with acarbose. And GLP-1 may act on the liver to modulate its production of FGF21 and IGF-I, thereby promoting longevity. The benefits of acarbose are likely mimicked by diets featuring slowly-digested 'lente' carbohydrate, and by certain nutraceuticals which can slow carbohydrate absorption. Prebiotics that promote colonic generation of short-chain fatty acids represent an alternative strategy for boosting intestinal GLP-1 production. The health benefits of all these measures presumably would be potentiated by concurrent use of dipeptidyl peptidase 4 inhibitors, which slow the proteolysis of GLP-1 in the blood. PMID:25685364

  2. Acute effects of acarbose on post-prandial glucose and triglycerides in type 2 diabetics following intake of different Malaysian foods.

    Nawawi, H M; Yazid, T N; Ismail, F; Khalid, B A

    2000-03-01

    Acarbose inhibits intestinal alpha-glucosidases resulting in diminished and delayed postprandial hyperglycaemia (PPH). Studies on effects of acarbose on postprandial lipaemia (PPL) have been inconclusive. Little is known about the effects of acarbose on PPH and PPL following intake of a polysaccharide diet. We studied 30 type 2 diabetic patients on dietary and/or oral hypoglycaemic agent(s). Thirty patients were recruited for food A (nasi lemak), 28 for food B (mee goreng) and 28 for food C (roti telur), which represent the typical diets of the three main races in Malaysia. Serial blood samples were taken at 15 min before and up to 240 min after each food intake, without acarbose. Subsequently, three doses of 50 mg acarbose were given orally and the same procedure was repeated the following day. There were significantly lower mean increments in plasma glucose levels after compared to before acarbose treatment 30, 45 and 60 min for food A and at 30, 45, 60, 120, 180 and 240 min for food C, but no significant difference was noted for food B. There was a significantly lower mean fasting glucose level after compared with before acarbose treatment following intake of food A and C but not food B. Short-term treatment with acarbose caused significant diminished and delayed PPH response with food A and C but not with food B. Acarbose was more effective in reducing PPH response in polysaccharide foods with a higher and earlier postprandial glucose peak than in those with a lower and lagged peak. There were no significant differences in the mean fasting or postprandial triglyceride levels before and after acarbose treatment, following intake of all three foods for up to 4 hours. Depending on the food absorption pattern, overnight low dose treatment with acarbose leads to diminished fasting and peak plasma glucose levels, and delayed PPH but insignificant reduction in postprandial lipaemia in poorly controlled type 2 diabetics following intake of racially different Malaysian

  3. Effect of Acarbose on Long-Term Prognosis in Acute Coronary Syndromes Patients with Newly Diagnosed Impaired Glucose Tolerance

    Peng Yun

    2016-01-01

    Full Text Available Objective. To investigate the effect of acarbose therapy on the long-term prognosis of patients with acute coronary syndromes (ACS complicating newly diagnosed impaired glucose tolerance (IGT. Methodology. 135 patients hospitalized for ACS who had been newly diagnosed with IGT were randomly assigned to acarbose group (150 mg/day, n=67 or control group (no acarbose, n=68. All cases in each group were given the same elementary treatment. Mean follow-up was 2.3 years. The incidence of major adverse cardiovascular event (MACE and carotid intima-middle thickness (CIMT were statistically analyzed. Results. During the mean follow-up of 2.3 years, the risk of recurrent MACE in acarbose group was decreased significantly compared with that in control group (26.67% versus 46.88%, P<0.05; at the same time, thickening of the CIMT was significantly slower than the control group ((1.28 ± 0.42 mm versus (1.51 ± 0.64 mm, P<0.05. Conclusions. Acarbose can effectively reduce the risk of MACE in ACS patients with newly diagnosed IGT, simultaneously retarding the progression of carotid intima-media thickness.

  4. Acarbose Treatment and the Risk of Cardiovascular Disease in Type 2 Diabetic Patients: A Nationwide Seven-Year Follow-Up Study

    Jui-Ming Chen

    2014-01-01

    Full Text Available Objective. To investigate the potential benefits of acarbose treatment on cardiovascular disease (CVD in patients with type 2 diabetes by using nationwide insurance claim dataset. Research Design and Methods. Among 644,792 newly diagnosed type 2 diabetic patients without preexisting CVD in a nationwide cohort study, 109,139 (16.9% who had received acarbose treatment were analyzed for CVD risk. Those with CVD followed by acarbose therapy were also subjected to analysis. Result. During 7 years of follow-up, 5,081 patients (4.7% developed CVD. The crude hazard ratio (HR and adjusted HR were 0.66 and 0.99, respectively. The adjusted HR of CVD was 1.19, 0.70, and 0.38 when the duration of acarbose use was 24 months, respectively. Adjusted HR was 1.14, 0.64, and 0.41 with acarbose cumulative doses 109,500 mg, respectively. Conclusion. In patients with type 2 diabetes without preexisting CVD, treatment with acarbose showed a transient increase in incidence of CVD in the initial 12 months followed by significant reductions of CVD in prolonged acarbose users. After the first CVD events, continuous use of acarbose revealed neutral effect within the first 12 months. The underlying mechanisms require further investigations.

  5. INFLUENCE OF ACARBOSE ON POSTPRANDIAL DYSMETABOLISM: RESULTS OF AN OPEN-LABEL RANDOMIZED STUDY

    A. Ya. Cherniak

    2015-09-01

    Full Text Available Aim. To evaluate postprandial changes of lipid and glucose profiles, inflammation markers levels and flow-mediated vasodilatation in patients with metabolic syndrome (MS and to estimate acarbose course treatment efficacy in glucose intolerant patients.Material and methods. A total of 114 MS patients (83 men, 31 women were examined, MS was associated with impaired glucose tolerance (IGT in 55 cases. At the first stage postpran- dial dynamics of flow-mediated dilation (FMD, lipid profile parameters, inflammation markers and insulin levels were estimated. At the second stage patients with MS and IGT (n=55 were randomly assigned to the two groups of treatment. Patients of the first group (n=28 had non-drug treatment. Patients of the second group (n=27 received acarbose 300 mg/day for 3 months in addition to recommendations for lifestyle change. 3 months later postprandial values of lipid and glucose profiles parameters, inflammation markers levels and FMD were reassessed. Results. MS patients with IGT revealed maximal disorders in metabolic parameters during postprandial period: increase in the plasma levels of total cholesterol by 6.1%, high density lipoproteins – by 1.7%, and triglycerides – by 27.87%, increase in atherogenic index by 4.8%, and plasma concentrations of glucose – by 54.7%, insulin – by 30.2%, HOMA index – by 73.3%, as well as concentrations of C-reactive protein (CRP – by 49.7%, tumor necrose factor alpha – by 20.8%, and interleukin-6 (IL-6 – by 51.9%. FMD decreased by 34.3%.After 12 weeks of the acarbose treatment we had revealed positive dynamics of studied indices in postprandial period as compared to an only non-drug management: levels of glucose in- creased by 24.1% vs 44.4%, insulin – by 14.4% vs 24.4%, CRP – by 19.9% vs 36.6%, IL-6 – by 25.1% vs 41.7%; postprandial FMD decreased by 18.9% vs 31.1%.Conclusion. Prescription of acarbose 300 mg/day for 12 weeks in glucose intolerant patients is characterized

  6. Structure of Bacillus halmapalus alpha-amylase crystallized with and without the substrate analogue acarbose and maltose

    Lyhne-Iversen, Louise; Hobley, Timothy John; Kaasgaard, Svend G.;

    2006-01-01

    Recombinant Bacillus halmapalus alpha-amylase (BHA) was studied in two different crystal forms. The first crystal form was obtained by crystallisation of BHA at room temperature in the presence of acarbose and maltose - data was collected at cryogenic temperatures to a resolution of 1.9 Å. It was...

  7. Effect of basal insulin combined with acarbose on blood glucose level and complications in patients with newly diagnosed elderly diabetes

    Yu-Qing Guo; Chen-Ru Zhang; Ai-Ge Yang; Fan Liu; Shan-Shan Dong; Yan Kang

    2016-01-01

    Objective:To analyze the effect of basal insulin combined with acarbose on blood glucose level and complications in patients with newly diagnosed elderly diabetes.Methods:A total of 135 cases of patients with newly diagnosed elderly diabetes who were treated in our hospital from July 2012 to January 2015 were enrolled as research subjects and divided into observation group 66 cases and control group 69 cases according to different treatment methods. Control group received acarbose therapy alone, observation group received basal insulin combined with acarbose therapy, and then differences in blood glucose level, oxidative stress indicators, nerve conduction velocity, vascular injury and inflammatory factor levels of two groups were compared.Results:FPG, 2hPG and HbA1C levels of observation group after treatment were lower than those of control group; AGE-P, MDA and NADPH levels were lower than those of control group, and SOD level was higher than that of control group; median MNCV, ulnar MNCV, tibial MNCV, median SNCV and sural SNCV levels were higher than those of control group; sVCAM-1, hs-CRP and IL-6 levels were lower than those of control group. Conclusion:Basal insulin combined with acarbose therapy for patients with newly diagnosed elderly diabetes can effectively optimize the levels of blood glucose and complication-related factors, and it has active clinical significance.

  8. Structure of a Bacillus halmapalus family 13 ά-amylase, BHA, in complex with an acarbose-derived nonasaccharide at 2.1 A resolution

    Davies,G.; Brzozowski, A.; Dauter, Z.; Rasmussen, M.; Borchert, T.; Wilson, K.

    2005-01-01

    The enzymatic digestion of starch by {alpha}-amylases is one of the key biotechnological reactions of recent times. In the search for industrial biocatalysts, the family GH13 {alpha}-amylase BHA from Bacillus halmapalus has been cloned and expressed. The three-dimensional structure at 2.1 Angstrom resolution has been determined in complex with the (pseudo)tetrasaccharide inhibitor acarbose. Acarbose is found bound as a nonasaccharide transglycosylation product spanning the -6 to +3 subsites. Careful inspection of electron density suggests that the bound ligand could not have been formed through successive transglycosylations of acarbose and must also have featured maltose or maltooligosaccharides as an acceptor.

  9. Pneumatosis cystoides intestinalis of the ascending colon related to acarbose treatment: a case report

    Vogel Yilin

    2009-09-01

    Full Text Available Abstract Introduction Pneumatosis cystoides intestinalis is characterized by the presence of multiple gas-filled cysts in the intestinal wall, the submucosa and/or subserosa of the intestine. The term pneumatosis cystoides coli is synonymous with pneumatosis cystoides intestinalis when the disorder is limited to the colon. It is a secondary finding caused by a wide variety of underlying gastrointestinal or extragastrointestinal diseases but rarely occurs in the course of treatment with an α-glucosidase inhibitor. This is the first report of pneumatosis cystoides intestinalis after 12 years of treatment with the α-glucosidase inhibitor acarbose. Case presentation A 65-year-old Caucasian German woman was referred to our hospital for hemicolectomy. She had been treated for type 2 diabetes mellitus with an α-glucosidase inhibitor (acarbose, 150 mg daily for 12 years. Three months before referral, she had complained of left abdominal pain. 'Polyposis coli' in the ascending colon and diverticulosis were diagnosed. Colonoscopy and computed tomography scans of the abdomen were repeated and revealed pneumatosis cystoides coli located in the ascending colon, whereas diverticulosis of the sigmoid colon was confirmed. Histological examination of a biopsy specimen only showed colon mucosa. After discontinuing administration of the α-glucosidase inhibitor for 3 months and on repeated colonoscopy, the polypoid lesions had completely disappeared. Conclusion This case illustrates that pneumatosis cystoides coli can be a source of diagnostic confusion. Pneumatosis cystoides coli must be considered in the initial differential diagnosis of patients especially in the presence of multiple colonic polypoid lesions. It is important to take pneumatosis cystoides intestinalis into consideration when prescribing α-glucosidase inhibitors to patients with diabetes who have diabetic autonomic neuropathy with decreased intestinal motility, or to patients taking steroids.

  10. An observational study of acarbose treatment in patients with type 2 diabetes from the Middle East and Morocco

    Shihabi AR

    2013-04-01

    Full Text Available Abdul R Shihabi,1 Essam M Moussa,2 Hania Sobierajska,3 Birgit Schmidt4 1Al Ain Centre, Dubai, United Arab Emirates; 2New Jeddah Hospital, Jeddah, Saudi Arabia; 3Etihad Airways Medical Centre, Abu Dhabi, United Arab Emirates; 4Bayer Schering Pharma AG, Leverkusen, Germany Background: The prevalence of type 2 diabetes is increasing dramatically in the Middle East and North Africa region. However, there are few trials that have determined the effect of antidiabetic treatment in an observational setting in these countries. Methods: This was a noninterventional study performed in Morocco in 2006–2007 and in the Middle East in 2005–2006 to observe the efficacy and safety of acarbose in patients with pretreated or untreated type 2 diabetes. Glycemic parameters (fasting blood glucose, one-hour postprandial blood glucose, and HbA1c were recorded within a 3-month period. The observation period included an initial visit at the start of acarbose therapy and up to three follow-ups. Results: Acarbose was effective in reducing glycemic parameters in patients from Morocco (n = 1082 and the Middle East (n = 1737. The mean one-hour postprandial blood glucose decreased by 35.5% to 165.4 ± 47.9 mg/dL in the Middle East and by 35.5% to 179.0 ± 49.9 mg/dL in Morocco. Mean fasting blood glucose decreased by 30.8% to 126.6 ± 34.2 mg/dL (Middle East and by 34.5% to 150.6 ± 47.1 mg/dL (Morocco. The absolute reduction in HbA1c was 1.3% in the Middle East (final value 7.4% and 1.0% in Morocco (final value 7.5%. Overall, 107 patients (Middle East and 26 patients (Morocco experienced minor drug-related adverse events, which were mainly gastrointestinal. The tolerability of acarbose was rated as very good/good by 80.8% in the Middle East and by 68.6% in Morocco. Conclusion: This study illustrates the efficacy and safety of acarbose in the treatment of type 2 diabetic patients in an observational setting. Keywords: type 2 diabetes, acarbose, Glucobay®, Glucor

  11. Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

    Kim, Ji-Hyun; Ahn, Ji-Hyun; Kim, Soo-Kyung; Lee, Dae-Ho; Kim, Hye-Soon; Shon, Ho-Sang; Jeon, Hyun-Jeong; Kim, Tae-Hwa; Cho, Yong-Wook; Kim, Jae-Taek; Han, Sung-Min; Chung, Choon-Hee; Ryu, Ohk-Hyun; Lee, Jae-Min; Lee, Soon-Hee

    2014-01-01

    Aims/Introduction Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. Materials and Methods The present study was a...

  12. The Effects of Gliclazide, Metformin, and Acarbose on Body Composition in Patients with Newly Diagnosed Type 2 Diabetes Mellitus ☆

    Hua WANG; Ni, Yafang; Yang, Shuo; Li, Huizhi; Li, Xu; Feng, Bo

    2013-01-01

    Background Although numerous clinical trials have evaluated the body weight change achieved using diabetes medications alone or in combinations, the composition of body weight change in these clinical trials has rarely been assessed. Objective We aimed to evaluate the effects of gliclazide, metformin, and acarbose monotherapy on body composition, fat distribution, and other cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. Methods A total of 86 patients with newly...

  13. Evaluation of effect of acarbose consumption on weight losing in non-diabetic overweight or obese patients in Kerman

    Akram Nakhaee

    2013-01-01

    Full Text Available Background: High prevalence of obesity and the importance of this issue as a risk factor for chronic diseases such as severe cardiovascular diseases, diabetes, and cancer necessitate the need for treatment. The aim of this study was the evaluation of acarbose effect on the weight loss in non diabetic overweight or obese patients in Kerman. Materials and Methods: A double blind randomized controlled clinical trial was performed on 66 patients with the body mass index (BMI between 25 and 35 kg/m2. Patients were divided in treatment and control groups using the randomization. The treatment group took 100 mg acarbose 3 times a day for 20 weeks in combination with the low calorie diet and exercise. Control group was given placebo, low calorie diet, and exercise. BMI was measured after 20 weeks. The analyses were carried out using t test and repeated measured ANOVA. Results: Patients in acarbose and placebo group had a non significant difference in BMI at baseline. Reducing in weight was considered in every month in both groups, but this reduction was higher in the treatment group. At the 5th month, the difference of BMI in the treatment group was significantly lower than the placebo group (2.31 ± 0.6 vs. 0.76 ± 0.6 kg/m2, P < 0.001. Conclusion: Acarbose, especially in combination with the low calorie diet and exercise, seems to lose weight effectively in obese and overweight patients in communities that have a high carbohydrate intake (like Persian diet.

  14. Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes

    Kim, Ji-Hyun; Ahn, Ji-Hyun; Kim, Soo-Kyung; Lee, Dae-Ho; Kim, Hye-Soon; Shon, Ho-Sang; Jeon, Hyun-Jeong; Kim, Tae-Hwa; Cho, Yong-Wook; Kim, Jae-Taek; Han, Sung-Min; Chung, Choon-Hee; Ryu, Ohk-Hyun; Lee, Jae-Min; Lee, Soon-Hee; Kwon, Min-Jeong; Kim, Tae-kyun; Namgoong, Il-Seong; Kim, Eun-Sook; Jung, In-Kyung; Moon, Sung-Dae; Han, Je-Ho; Kim, Chong-Hwa; Cho, Eun-Hee; Kim, Ki-Young; Park, Hee-Baek; Lee, Ki-Sang; Lee, Sung-Woo; Lee, Sang-Cheol; Kang, Cheol-Min; Jeon, Byung-Sook; Song, Min-Seop; Yun, Seung-Baik; Chung, Hyung-Keun; Seong, Jong-Ho; Jeong, Jin-Yi; Cha, Bong-Yun

    2015-01-01

    Aims/Introduction Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. Materials and Methods The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. Results Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were ‘very satisfied’ or ‘satisfied’ with the combined basal insulin and acarbose therapy. Conclusions Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone. PMID:25802730

  15. Effects of nateglinide and acarbose on glycemic excursions in standardized carbohydrate and mixed-meal tests in drug-naïve type 2 diabetic patients

    LI, HAI; XU, WENMING; LIU, JUAN; CHEN, AILING; LIAO, ZHIHONG; LI, YANBING

    2013-01-01

    The aim of this study was to compare the effects of nateglinide and acarbose on glycemic excursions and postprandial glucose profiles with different types of meals (standardized carbohydrate and mixed meals) in drug-naïve type 2 diabetic patients. A randomized, parallel-group prospective design clinical trial was conducted and a total of 39 drug-naïve patients (16 males and 23 females, aged 56.7±10.2 years) were enrolled. The patients were randomly divided into group A [nateglinide 120 mg three times daily (t.i.d.), n=19] and group B (acarbose 50 mg t.i.d., n=20). The standardized carbohydrate and mixed-meal tests were performed at baseline and at the end of study. Continuous glucose monitoring system (CGMS) data were recorded. Various parameters that measure glucose variability were derived from the CGMS data. In the standardized carbohydrate meal tests, the postprandial glucose excursions (PPGEs) were significantly decreased in the two groups after 12 weeks of treatment (P0.05). In conclusion, nateglinide and acarbose effectively improved postprandial glycemic control, although acarbose was shown to be more efficient in controlling early (30 and 60 min) postprandial glucose excursions in the carbohydrate meal test, whereas nateglinide was shown to be superior to acarbose in controlling postprandial glucose excursions in the mixed-meal test. PMID:24649052

  16. Comparison of Acarbose and Voglibose in Diabetes Patients Who Are Inadequately Controlled with Basal Insulin Treatment: Randomized, Parallel, Open-Label, Active-Controlled Study

    Lee, Mi Young; Choi, Dong Seop; Lee, Moon Kyu; Lee, Hyoung Woo; Park, Tae Sun; Kim, Doo Man; Chung, Choon Hee; Kim, Duk Kyu; Kim, In Joo; Jang, Hak Chul; Park, Yong Soo; Kwon, Hyuk Sang; Lee, Seung Hun; Shin, Hee Kang

    2013-01-01

    We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decrea...

  17. Utility of an oxidation reaction for the spectrophotometric determination of acarbose in controlled release tablets at various simulated gastrointestinal media.

    Sinha, Vivek Ranjan; Kumar, Ruchita V

    2012-01-01

    A sensitive kinetic method for spectrophotometric determination of acarbose is developed and validated for the determination of the drug in bulk and pharmaceutical formulations. The drug was estimated in simulated gastrointestinal media i.e., 0.1 M HCl (pH 1.2) and phosphate buffer (pH 6.8). The method involves the oxidation of acarbose by treating it with a strong oxidizing agent (potassium permanganate (1 x 10(-2) M)) in alkaline media. The reaction kinetics was determined for 20 min at room temperature. The reaction followed first order kinetics and the absorbance of the corresponding manganate ions produced was determined at 610 nm. The absorbance-concentration plot was found to be rectilinear over the concentration range of 2-20 microg/mL. The proposed method was used for estimation of the drug in a novel controlled release dosage form. Thus, the method developed was simple, reproducible and can be successfully applied for the determination of the drug in simulated gastrointestinal fluid. PMID:22574503

  18. Transglycosylation reactions of Bacillus stearothermophilus maltogenic amylase with acarbose and various acceptors

    It was observed that Bacillus stearothermophilus maltogenic amylase cleaved the first glycosidic bond of acarbose to produce glucose and a pseudotrisaccharide (PTS) that was transferred to C-6 of the glucose to give an α-(1-6) glycosidic linkage and the formation of isoacarbose. The addition of a number of different carbohydrates to the digest gave transfer products in which PTS was primarily attached α-(1-6) to d-glucose, d-mannose, d-galactose, and methyl α-d-glucopyranoside. With d-fructopyranose and d-xylopyranose, PTS was linked α-(1-5) and α-(1-4), respectively. PTS was primarily transferred to C-6 of the nonreducing residue of maltose, cellobiose, lactose, and gentiobiose. Lesser amounts of α-(1-3) and/or α-(1-4) transfer products were also observed for these carbohydrate acceptors. The major transfer product to sucrose gave PTS linked α-(1-4) to the glucose residue. α,α-Trehalose gave two major products with PTS linked α-(1-6) and α-(1-4). Maltitol gave two major products with PTS linked α-(1-6) and α-(1-4) to the glucopyranose residue. Raffinose gave two major products with PTS linked α-(1-6) and α-(1-4) to the d-galactopyranose residue. Maltotriose gave two major products with PTS linked α-(1-6) and α-(1-4) to the nonreducing end glucopyranose residue. Xylitol gave PTS linked α-(1-5) as the major product and d-glucitol gave PTS linked α-(1-6) as the only product. The structures of the transfer products were determined using thin layer-chromatography, high-performance ion chromatography, enzyme hydrolysis, methylation analysis and 13C NMR spectroscopy. The best acceptor was gentiobiose, followed closely by maltose and cellobiose, and the weakest acceptor was d-glucitol. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  19. Randomized, Double-Blinded, Double-Dummy, Active-Controlled, and Multiple-Dose Clinical Study Comparing the Efficacy and Safety of Mulberry Twig (Ramulus Mori, Sangzhi) Alkaloid Tablet and Acarbose in Individuals with Type 2 Diabetes Mellitus

    Chen, Yao

    2016-01-01

    Aims. To evaluate the efficacy and safety of mulberry twig alkaloid (SZ-A) tablet compared with acarbose in patients with type 2 diabetes. Methods. This clinical trial enrolled 38 patients who were randomized into two groups (SZ-A: 23; acarbose: 15) and were treated for 24 weeks. Patients and clinical trial staffs were masked to treatment assignment throughout the study. The primary outcome measures were glycated hemoglobin (HbA1c) and 1-hour and 2-hour postprandial and fasting plasma glucose levels from baseline to the end of treatment. Analysis included all patients who completed this study. Results. By the end of this study, HbA1c level in SZ-A group was decreased from baseline significantly (P < 0.001). No significant difference was found when compared with acarbose group (P = 0.652). Similarly, 1-hour and 2-hour postprandial plasma glucose levels in SZ-A group were decreased from baseline statistically (P < 0.05), without any significant differences compared with acarbose group (P = 0.748 and 0.558, resp.). The fasting plasma glucose levels were not significantly changed in both groups. One of 23 patients in SZ-A group (4.76%) and 5 of 15 patients in acarbose group (33.33%) suffered from gastrointestinal adverse events. Conclusions. Compared with acarbose, SZ-A tablet was effective and safe in glycemic control in patients with type 2 diabetes. PMID:27547230

  20. Combined Effects of Green Tea Extracts, Green Tea Polyphenols or Epigallocatechin Gallate with Acarbose on Inhibition against α-Amylase and α-Glucosidase in Vitro

    Yiqi Wang; Danielle Hochstetter; Ping Xu; Yuefei Wang; Junjie Gao

    2013-01-01

    Green tea, green tea polyphenols and epigallocatechin gallate (EGCG) are confirmed to have beneficial effects in the treatment of diabetes mellitus, and a possible mechanism can be ascribed to their inhibitory effect against α-amylase and α-glucosidase in the digestive tract. In this paper, we first investigated the combined inhibitory effect of green tea extracts, green tea polyphenols or EGCG with acarbose on α-amylase and α-glucosidase in vitro. Our results indicated that the interaction b...

  1. Alpha-glucosidase inhibitor, acarbose, improves glycamic control and reduces body weight in type 2 diabetes: Findings on indian patients from the pooled data analysis

    Sanjay Kalra

    2013-01-01

    Full Text Available Alpha-glucosidase inhibitors are widely used especially in Asian countries as a treatment option for type 2 diabetes patients with high postprandial glycemia (PPG. The higher carbohydrate in the Indian diets lead to greater prandial glycemic excursion, increased glucosidase, and incretin activity in the gut and may need special therapeutic strategies to tackle these glucose peaks. This is the subgroup analysis of Indian subjects who participated in the GlucoVIP study that investigated the effectiveness and tolerability of acarbose as add-on or monotherapy in a range of patients with type 2 diabetes mellitus. A total of 1996 Indian patients were included in the effectiveness analysis. After 12.5 weeks (mean, the mean change in 2-hour PPG from baseline was −74.4 mg/dl, mean HbA1c decreased by -1.0%, and mean fasting blood glucose decreased by -37.9 mg/dl. The efficacy of acarbose was rated "very good" or "good" in 91.1% of patients, and tolerability as "very good" or "good" in 88.0% of patients. The results of this observational study suggest that acarbose was effective and well tolerated in the Indian patients with T2DM.

  2. alpha-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7-36 amide) and to delay gastric emptying in Type 2 diabetic patients

    Hücking, K; Kostic, Z; Pox, C;

    2005-01-01

    AIM: Acarbose is able to enhance GLP-1 release and delay gastric emptying in normal subjects. The effect of alpha-glucosidase inhibition on GLP-1 has been less evident in Type 2 diabetic patients. The aim of this study was to investigate the possible influence of acarbose on GLP-1 release...... and gastric emptying in Type 2 diabetic patients after a mixed test meal. PATIENTS AND METHODS: Ten Type 2 diabetic patients were tested with 100 mg acarbose or placebo served with a mixed meal that was labelled with 100 mg 13C-octanoic acid. Plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP......-1 and GIP were determined over 6 h. Gastric emptying was measured by determining breath 13CO2 using infrared absorptiometry. Statistics repeated-measures anova. RESULTS: Gastric emptying rates (t1/2: 162 +/- 45 vs. 163 +/- 62 min, P = 0.65) and plasma concentrations (increasing from approximately 12...

  3. Effects of acarbose on ruminal fermentation, blood metabolites and microbial profile involved in ruminal acidosis in lactating cows fed a high-carbohydrate ration.

    Blanch, Marta; Calsamiglia, Sergio; Devant, Maria; Bach, Alex

    2010-02-01

    The objective was to evaluate the effects of an inhibitor of alpha-amylase and glucosidase (acarbose, Pfizer Limited, Corby, UK) on ruminal fermentation, blood metabolism and microbial profile in dairy cows in a 2x2 cross-over experiment. Eight Holstein cows fitted with rumen cannulas (milk yield, 24.3+/-2.35 kg/d, body weight, 622+/-54 kg, days in milk, 183+/-67, 5 multiparous and 3 primiparous) were used. Treatments were: control (no additive, CTR) and alpha-amylase and glucosidase inhibitor (0.75 g acarbose-premix/cow per d, AMI). Animals were given ad-libitum access to a high non-fibre carbohydrate (NFC) partial mixed ration (PMR) containing 17.6% crude protein, 28.3% neutral detergent fibre, and 46.5% NFC in the dry matter and supplementary concentrate during milking. Blood samples were taken to determine blood glucose, insulin and urea within the first hour after the morning feeding on two separate days in each period. Samples of ruminal contents were collected during 3 d in each period at 0, 4 and 8 h after feeding to determine volatile fatty acid and ammonia-N concentrations and to quantify protozoa, Streptococcus bovis and Megasphaera elsdenii. Rumen pH was recorded electronically at 22-min intervals during 6 d in each period. Results were analysed using a mixed-effects model. Cows on AMI treatment spent less time with ruminal pH bovis to Meg. elsdenii ratio than CTR (4.09 and 26.8+/-12.0, respectively). These results indicate that dietary supplementation with acarbose in dairy cattle fed high-production rations may be effective in reducing the time for which rumen pH is suboptimal, with no negative effects on ruminal fermentation and blood metabolites. PMID:20053317

  4. Untersuchungen zum Einbau des Stickstoffes in der Acarviose-Einheit der Acarbose bei [Actinoplanes] sp. 50/110: die Aminotransferase Acb

    Diaz-Guardamino Uribe, Paz Marta

    2001-01-01

    Diese Arbeit befasste sich mit dem Stickstoffstoffwechsel bei Actinoplanes sp. unter besonderer Berücksichtigung der Frage, wie der Stickstoff in den alpha-Glucosidaseinhibitor Acarbose während der Biogenese eingeführt wird. Zu klären galt es welches der postulierten Intermediate der Biosynthese transaminiert und durch welches Enzym diese Reaktion katalysiert wird. Heterologe PCR führte zur Identifizierung der Glutaminsynthetasen kodierenden Gene glnA und glnII auf dem Genom von Actinopla...

  5. Effects of nateglinide and acarbose on glycemic excursions in standardized carbohydrate and mixed-meal tests in drug-naïve type 2 diabetic patients

    Li, Hai; Xu, Wenming; LIU, JUAN; Chen, Ailing; Liao, Zhihong; Li, Yanbing

    2013-01-01

    The aim of this study was to compare the effects of nateglinide and acarbose on glycemic excursions and postprandial glucose profiles with different types of meals (standardized carbohydrate and mixed meals) in drug-naïve type 2 diabetic patients. A randomized, parallel-group prospective design clinical trial was conducted and a total of 39 drug-naïve patients (16 males and 23 females, aged 56.7±10.2 years) were enrolled. The patients were randomly divided into group A [nateglinide 120 mg thr...

  6. Characterization of two coleopteran α-amylases and molecular insights into their differential inhibition by synthetic α-amylase inhibitor, acarbose.

    Channale, Sonal M; Bhide, Amey J; Yadav, Yashpal; Kashyap, Garima; Pawar, Pankaj K; Maheshwari, V L; Ramasamy, Sureshkumar; Giri, Ashok P

    2016-07-01

    Post-harvest insect infestation of stored grains makes them unfit for human consumption and leads to severe economic loss. Here, we report functional and structural characterization of two coleopteran α-amylases viz. Callosobruchus chinensis α-amylase (CcAmy) and Tribolium castaneum α-amylase (TcAmy) along with their interactions with proteinaceous and non-proteinaceous α-amylase inhibitors. Secondary structural alignment of CcAmy and TcAmy with other coleopteran α-amylases revealed conserved motifs, active sites, di-sulfide bonds and two point mutations at spatially conserved substrate or inhibitor-binding sites. Homology modeling and molecular docking showed structural differences between these two enzymes. Both the enzymes had similar optimum pH values but differed in their optimum temperature. Overall, pattern of enzyme stabilities were similar under various temperature and pH conditions. Further, CcAmy and TcAmy differed in their substrate affinity and catalytic efficiency towards starch and amylopectin. HPLC analysis detected common amylolytic products like maltose and malto-triose while glucose and malto-tetrose were unique in CcAmy and TcAmy catalyzed reactions respectively. At very low concentrations, wheat α-amylase inhibitor was found to be superior over the acarbose as far as complete inhibition of amylolytic activities of CcAmy and TcAmy was concerned. Mechanism underlying differential amylolytic reaction inhibition by acarbose was discussed. PMID:27132147

  7. Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

    Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

    2016-06-01

    Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (pcats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. PMID:27234550

  8. Isolation, characterization and inhibition by acarbose of the alpha-amylase from Lactobacillus fermentum: comparison with Lb. manihotivorans and Lb. plantarum amylases.

    Talamond, P; Desseaux, V; Moreau, Y; Santimone, M; Marchis-Mouren, G

    2002-11-01

    Extracellular alpha-amylase from Lactobacillus fermentum (FERMENTA) was purified by glycogen precipitation and ion exchange chromatography. The purification was approximately 28-fold with a 27% yield. The FERMENTA molecular mass (106,000 Da) is in the same range as the ones determined for L. amylovorus (AMYLOA), L. plantarum (PLANTAA) and L. manihotivorans (MANIHOA) alpha-amylases. The amino acid composition of FERMENTA differs from the other lactobacilli considered here, but however, indicates that the peptidic sequence contains two equal parts: the N-terminal catalytic part; and the C-terminal repeats. The isoelectric point of FERMENTA, PLANTAA, MANIHOA are approximately the same (3.6). The FERMENTA optimum pH (5.0) is slightly more acidic and the optimum temperature is lower (40 degrees C). Raw starch hydrolysis catalyzed by all three amylases liberates maltotriose and maltotretaose. Maltose is also produced by FERMENTA and MANIHOA. Maltohexaose FERMENTA catalyzed hydrolysis produces maltose and maltotriose. Finally, kinetics of FERMENTA, PLANTAA and MANIHOA using amylose as a substrate and acarbose as an inhibitor, were carried out. Statistical analysis of kinetic data, expressed using a general velocity equation and assuming rapid equilibrium, showed that: (1) in the absence of inhibitor k(cat)/Km are, respectively, 1x10(9), 12.6x10(9) and 3.2x10(9) s(-1) M(-1); and (2) the inhibition of FERMENTA is of the mixed non-competitive type (K(1i)=5.27 microM; L(1i)=1.73 microM) while the inhibition of PLANTAA and MANIHOA is of the uncompetitive type (L(1i)=1.93 microM and 1.52 microM, respectively). Whatever the inhibition type, acarbose is a strong inhibitor of these Lactobacillus amylases. These results indicate that, as found in porcine and barley amylases, Lactobacillus amylases contain in addition to the active site, a soluble carbohydrate (substrate or product) binding site. PMID:12431403

  9. Inhibitory activity of cinnamon bark species and their combination effect with acarbose against intestinal α-glucosidase and pancreatic α-amylase.

    Adisakwattana, Sirichai; Lerdsuwankij, Orathai; Poputtachai, Ubonwan; Minipun, Aukkrapon; Suparpprom, Chaturong

    2011-06-01

    Inhibition of α-glucosidase and pancreatic α-amylase is one of the therapeutic approaches for delaying carbohydrate digestion, resulting in reduced postprandial glucose. The aim of this study was to evaluate the phytochemical analysis and the inhibitory effect of various cinnamon bark species against intestinal α-glucosidase and pancreatic α-amylase. The results showed that the content of total phenolic, flavonoid, and condensed tannin ranged from 0.17 to 0.21 g gallic acid equivalent/g extract, from 48.85 to 65.52 mg quercetin equivalent/g extract, and from 0.12 to 0.15 g catechin equivalent/g extract, respectively. The HPLC fingerprints of each cinnamon species were established. Among cinnamon species, Thai cinnamon extract was the most potent inhibitor against the intestinal maltase with the IC(50) values of 0.58 ± 0.01 mg/ml. The findings also showed that Ceylon cinnamon was the most effective intestinal sucrase and pancreatic α-amylase inhibitor with the IC(50) values of 0.42 ± 0.02 and 1.23 ± 0.02 mg/ml, respectively. In addition, cinnamon extracts produced additive inhibition against intestinal α-glucosidase and pancreatic α-amylase when combined with acarbose. These results suggest that cinnamon bark extracts may be potentially useful for the control of postprandial glucose in diabetic patients through inhibition of intestinal α-glucosidase and pancreatic α-amylase. PMID:21538147

  10. Effect of acarbose addition on acute and subacute rumen acidosis in an in vitro fermentation study%酸中毒条件下添加阿卡波糖对瘤胃微生物发酵的影响

    毛胜勇; 何文波; 朱伟云

    2012-01-01

    The effect of acarbose addition on ruminant fermentation was investigated in three experiments. In the first and second experiments, the effects of acarbose addition on subacute rumen acidosis was studied. The final concentration of acarbose in the media was 0, 0. 1, 0. 2 or 0. 4 mg/mL. In the first study, the substrate consisted of 0. 8 g cracked corn and 0. 2 g Chinese dry grass. As compared with the control, the acarbose addition increased the pH value and the ratio of acetate to propionate, and decreased acetate, propionate, butyrate, isobutyrate, total volatile fatty acid and lactic acid concentrations. In the second experiment, the substrates consisted of cracked sorghum, corn, barley and wheat. The acarbose supplement increased pH, NH3-N, lac-tate concentration and the ratio of the acetate to propionate, and decreased acetate, propionate, butyrate and TVFA concentration. In the third experiment, the effect of acarbose addition on acute rumen acidosis was investigated, the pH, acetate, propionate, acetate, propionate, valerate, isovalerate and TVFA concentrations were reduced by acarbose addition, while the pH value was improved. There were no significant changes in the isobutyrate, butyrate, and isovalerate concentrations. In general, these results indicated that acarbose addition increased the pH value and reduced lactic acid concentration, and it has the potential to prevent rumen acidosis.%利用体外培养技术,评估了急性与亚急性酸中毒条件下添加阿卡波糖对瘤胃微生物发酵的影响.设3个实验,实验1和实验2体外摸拟了亚急性酸中毒(5.0<pH<5.6)、实验3模拟了急性酸中毒条件(pH<5.0),各实验中阿卡波糖添加量均为0,0.1,0.2和0.4 mg/mL.实验1中底物组成为0.8g玉米和0.2g粉碎羊草,实验2以高梁、玉米、小麦和大麦为底物,实验3发酵底物为0.75g玉米、0.25g纤维二糖、0.25g甘露糖和0.25g木糖;各实验组均设4个重复,体外培养24h.结果表明,实验1

  11. 地特胰岛素联合阿卡波糖治疗2型糖尿病临床观察%Cinical observation of insulin detemir combined with acarbose in curing type 2 diabetic patients

    劳丹华; 黄剑娴

    2012-01-01

    Objective To observe the effect of insulin detemir combined with acarbose in treatment of patients with type 2 diabetes (T2DM).Methods 32 T2DM patients whose blood glucose control was poor receiving twice daily isophane protamine biosynthetic human insulin( Novolin 30R) combined or not combined with oral hypoglycemic drugs,were switched to receive insulin detemir injection once daily and oral acarbose three times daily for 12 weeks.By self-contrasted method,observed blood glucose before and after three meals,before sleeping,glycated hemoglobin ( HbA1c),change of body mass index( BMI),incidence of hypoglycemia,compliance and satisfaction of patients (by questionnaire) before and after treatment.Results After treatment,the blood glucose before and after three meals,before sleeping and HbA1 c declined sigmifieatly ( t =11.212,14.997,10.863,17.950,11.108,14.034,12.422,22.764,all P <0.01 )compared to state before treatment.The rate of hypoglycemia in the day was 3.1%,without nocturnal symptoms of hypoglycemia.BMI had certain declining,but there was no statistical significance (P > 0.05).The compliance and satisfaction of patients were in a higher rate (x2 =10.255,9.143,all P < 0.01 ).Conclusion Insulin detemir combined with acarbose could effectively control the blood glucose,incidence of hypoglycemia,without increasing body mass,achieve good compliance and satisfaction of patients.%目的 观察地特胰岛素联合阿卡波糖治疗2型糖尿病的临床疗效.方法 对32例经预混精蛋白生物合成人胰岛素治疗血糖控制不佳的2型糖尿病患者,采用地特胰岛素每天1次注射,联合阿卡波糖,每天3次口服,治疗12周,采用自身对照,观察治疗前后三餐前、三餐后、睡前血糖、糖化血红蛋白(HbA1c)水平、体质量指数(BMI)变化及低血糖发生情况、患者治疗依从性和满意率.结果 治疗后三餐前、三餐后及睡前血糖、HbA1c均比治疗前明显下降(t=11.212、14.997、10.863、17

  12. Clinical Observation of Insulin Detemir Combined Acarbose in Type 2 Diabetic Patients after Intensive Treatment%强化治疗后的2型糖尿病患者转地特胰岛素联合阿卡波糖治疗的临床观察

    祝恩梅

    2011-01-01

    目的 观察经持续皮下注射胰岛素(CSII)强化治疗的2型糖尿病(T2DM)患者改用地特胰岛素加阿卡波糖治疗的有效性、安全性及患者依从性.方法 将52例经CSII强化治疗达标的T2DM患者随机分为每日1次地特胰岛素+三餐口服阿卡波糖组和每日2次混合精蛋白锌重组人胰岛素组(优泌林70/30),各26例.12周后比较两组患者糖化血红蛋白(HbA1c),三餐前、三餐后及睡前血糖水平,患者依从性和满意率通过问卷调查来统计.结果 两组间HbA1c比较差异无统计学意义(P>0.05);地特胰岛素+阿卡波糖组中餐前与中餐后2 h血糖均低于精蛋白锌重组人胰岛素组,其差异有统计学意义(P<0.05),两组低血糖发生率相似,无统计学差异(P>0.05);地特胰岛素组患者的依从性和满意率明显高于精蛋白锌重组人胰岛素组.结论 CSII强化治疗后的T2DM患者改用地特胰岛素加阿卡波糖治疗有较好的疗效和安全性,患者依从性、满意率高.%Objective To observe the effectiveness, safety and patient compliance of type 2 diabetes ( T2DM )patients with continuous subcutaneous insulin infusion( CSⅡ )intensive treatment switching to detemir insulin therapy combined acarbose.Methods After intensive treatment by CSⅡ,52 patients with type 2 diabetes mellitus were randomly divided into two groups:detemir combined acarbose group and recombinant human hybrid protamine zinc insulin group.Detemir was given once daily and acarbose were orally given with three meals.Recombinant human hybrid protamine zinc insulin( Humulin 70/30 )were given twice daily.After 12 weeks treatment, we measured glycated hemoglobin( HbAlc )and blood glucose including before meals, after meals and before sleep.Patient compliance and satisfaction were estimated through questionnaires.Results HbA1 c between the two groups had no significant difference( P > 0.05 ).Blood glucose before meals and blood glucose 2 h after meals in detemir

  13. Coste-efectividad de la adición de acarbosa al tratamiento de pacientes con diabetes tipo 2 en España Cost-effectiveness of the addition of acarbose to the treatment of patients with type-2 diabetes in Spain

    Carme Piñol

    2007-04-01

    Full Text Available Objetivos: Evaluar el coste-efectividad de la adición de acarbosa al tratamiento de pacientes con diabetes mellitus tipo 2 (DM2 en España. Métodos: Se utilizó el CORE Diabetes Model (modelo de simulación informática publicado y validado para proyectar a largo plazo los resultados clínicos y de costes de la DM2. Las probabilidades de transición y los riesgos se obtuvieron de distintas publicaciones. Los efectos del tratamiento y las características basales de la cohorte se obtuvieron de un metaanálisis. Los costes directos se extrajeron de diversas publicaciones y se proyectaron a lo largo de la vida de los pacientes bajo la perspectiva del Sistema Nacional de Salud de España. Los costes y beneficios fueron descontados en un 3% anual. Se realizaron análisis de sensibilidad. Resultados: El tratamiento con acarbosa se asoció con mejoras en la esperanza de vida (0,23 años y en los años de vida ajustados por calidad (AVAC (0,21 años. Los costes directos fueron en promedio, por paciente, de 468 € más caros con acarbosa que con placebo. La razón de coste-efectividad incremental fue de 2.002 €/año de vida ganado y de 2.199 €/AVAC ganado. La curva de aceptabilidad mostró que con una disponibilidad a pagar de 20.000 €, generalmente aceptada como muy buen valor monetario, el tratamiento con acarbosa se asoció con una probabilidad del 93,5% de ser coste-efectiva. Conclusiones: Este estudio económico a largo plazo mostró que la adición de acarbosa al tratamiento de pacientes con DM2 produjo mejoras en la esperanza de vida y en los AVAC de estos pacientes.Objectives: To assess the cost-effectiveness of the addition of acarbose to existing treatment in patients with type 2 diabetes mellitus (DM2 in Spain. Methods: The CORE Diabetes Model (a published and validated computer simulation model was used to project long-term clinical and cost outcomes in DM2. Transition probabilities and risk adjustments were derived from published

  14. 基础胰岛素联合阿卡波糖对初诊老年糖尿病患者血糖水平及并发症的影响%Effect of basal insul in combined with acarbose on blood glucose level and compl ications in patients with newly diagnosed elderly diabetes

    郭玉卿; 张趁茹; 杨爱格; 刘璠; 董闪闪; 康岩; 王丽娜

    2016-01-01

    Objective:To analyze the effect of basal insulin combined with acarbose on blood glucose level and complica-tions in patients with newly diagnosed elderly diabetes.Methods:A total of 135 cases with newly diagnosed elderly diabetes who were treated in our hospital from July 2012 to January 201 5 were enrolled as research subjects and divided into observation group (66 cases)and control group (69 cases)according to different treatment methods.Control group received acarbose thera-py alone,observation group received basal insulin combined with acarbose therapy,and then differences in blood glucose level, oxidative stress indicators,nerve conduction velocity,vascular injury and inflammatory factor levels of two groups were com-pared.Results:FPG,2hPG and HbA1C levels of observation group after treatment were lower than those of control group (P<0.05);AGE-P,MDA and NADPH levels were lower than those of control group,and SOD level was higher than that of control group (P <0.05 );median MNCV,ulnar MNCV,tibial MNCV,median SNCV and sural SNCV levels were higher than those of control group (P <0.05);sVCAM-1,hs-CRP and IL-6 levels were lower than those of control group (P <0.05). Conclusion:Basal insulin combined with acarbose therapy for patients with newly diagnosed elderly diabetes can effectively opti-mize the levels of blood glucose and complication-related factors,and it has active clinical significance.%目的::分析基础胰岛素联合阿卡波糖对初诊老年糖尿病患者血糖水平及并发症情况的影响.方法:2012年7月~2015年1月间河北医科大学第一医院收治的初诊老年糖尿病患者135例作为研究对象,按照治疗方式不同分为观察组66例,对照组69例.对照组患者接受单纯阿卡波糖治疗,观察组患者接受基础胰岛素联合阿卡波糖治疗,对比两组患者的血糖水平、氧化应激指标、神经传导速度、血管损伤及炎症因子水平等差异.结果:治疗后观察组患者的 FPG

  15. Clinical curative effect and safety analysis of insulin glargine and acarbose treatment in elderly diabetes patients%甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性评价

    王筱景; 阮凌燕; 周小爱

    2014-01-01

    目的:评价甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性。方法老年糖尿病患者120例随机分为治疗组和对照组,各60例。治疗组用甘精胰岛素联合阿卡波糖,对照组用精蛋白生物合成人胰岛素注射液联合阿卡波糖,胰岛素始剂量为0.15 U・ kg-1,根据血糖水平调整胰岛素用量及口服药物用量,随访观察3个月。监测患者血糖水平,并记录不良事件;随访记录2组患者的血糖达标时间和每日胰岛素总量,计算日平均血糖,检测患者治疗后的糖化血红蛋白水平和空腹 C 肽值。结果治疗3个月后,患者的糖化血红蛋白、空腹血糖及日平均血糖水平较治疗前均降低(P <0.05),其中,治疗组的日平均血糖水平显著低于对照组(P <0.05)。治疗组的血糖达标时间和胰岛素日用量均少于对照组(P 均<0.05),治疗后空腹 C 肽含量明显高于对照组(P <0.05)。治疗组的不良反应发生率低于对照组(P <0.05)。结论甘精胰岛素联用阿卡波糖治疗老年糖尿病患者具有良好疗效,能快速、安全、有效地控制患者血糖。%Objective To study the clinical curative effect and safety analysis of insulin glargine with acarbose treatment in elderly patients with diabetes.Methods A total of 120 cases of elderly patients with diabetes were randomly divided into two groups.The 60 patients of treat-ment group were treated with insulin glargine and acarbose combination , and the 60 patients of the control group were treated with isophane prota -mine biosynthetic human insulin injection and acarbose combination .The patient monitored blood glucose levels and recorded adverse events .The therapeutic time and the daily amount of insulin were recorded of two groups of patients.The average daily blood sugar were calculated and the HbA1c and fasting c -peptide values were detected at 3 months

  16. The therapeutic effect of insulin glargine versu NPH insulin as add-on therapy to previous acarbose or metformin in senile obese type 2 diabetics%加用甘精胰岛素对老年肥胖2型糖尿病口服降糖药控制不佳患者的疗效

    王宾; 胡桂荣; 何丽; 孟红旗; 党静; 谢淑薏

    2012-01-01

    Objective To study the effectiveness and safety of insulin glargine versus isophane insulin as add-on therapy to previous OHA in senile obese type 2 diabetic patients who failed to control their blood glucose with oral hypoglycemic agents (OHA). Methods Sixty-one patients who failed to control their blood glucose with OHA were randomized into insulin glargine group and isophane insulin group. They were administered previous acarbose and/or metformin tablet and insulin glargine or isophand insulin as add-on therapy. The observation lasted for 12 weeks. Result (1) Both groups showed significant difference in HbAic FPG, and 2 hPG compared with before treatment, and in HbA1c and 2 hPG between the two groups (all P0. 05). (2) The BMI of the insulin glargine group was reduced by 2. 7 kg/m2 compared with before treatment) while that of the isophand insulin group was basically unchanged compared with before treatment (3) The 45. 2% of patients with insulin glargine treatment and the 73. 3% of patients with isophand insulin treatment had symptomatic hypoglycemia, and the difference was statistically significant (P<0. 05). (4) At the end of treatment, the dosa of insulin glargine group and isophand insulin group was (18. 7±3. 5) U/d and (26. 0±3. 7) U/d respectively, and the difference was statistically significant (P<0. 05). Conclusion The combination of insulin glargine with acarbose and/or metfonnin is effective in controlling the blood glucose, decreasing the incidence of hypoglycemia,and controlling the body weight of senile obese type 2 diabetic patients.%目的 研究口服降糖药控制不佳的老年肥胖T2DM患者加用甘精胰岛素或中效胰岛素联合应用治疗的有效性和安全性. 方法 将口服降糖药控制不佳的老年肥胖T2DM患者61例随机分为甘精胰岛素组和中效胰岛素组,治疗期内阿卡波糖和(或)二甲双胍剂量不变,分别加用甘精胰岛素或中效胰岛素每晚睡前注射1次联合治疗,进行12

  17. 门冬胰岛素30联和阿卡波糖与胰岛素4次皮下注射治疗2型糖尿病临床疗效观察%Clinical efficacy observation between insulin aspart 30 injection combined with acarbose and four-times-insulin subcu-taneous injection in patients with poorly-cntronlled type 2 diaetes

    胡艺琼; 陈晓文

    2014-01-01

    目的:比较单用门冬胰岛素(诺和锐)30血糖控制差的2型糖尿病患者加用阿卡波糖后和其改用四次胰岛素皮下注射方案的有效性、安全性。方法将医院60例单用诺和锐30血糖控制差的2型糖尿病患者随机分为2组,对照组30例采用诺和锐303次皮下注射同时3餐嚼服阿卡波糖;研究组30例采用4次胰岛素皮下注射(生物合成人胰岛素 R +地特胰岛素)。根据血糖调整胰岛素剂量,连续治疗12周后比较2组空腹血糖、餐后血糖、糖化血红蛋白(HbA1c)、胰岛素使用剂量及低血糖发生情况。结果2组空腹血糖,餐后血糖,HbA1c 都较前明显下降(P 0.05);对照组胰岛素用量明显减少,且低血糖发生率低,差异均有统计学意义(P 0. 05);The control group significantly reduced the amount of insulin,with lower incidence of hy-poglycemia,the differences were statistical significance(P < 0. 05). Conclusion NovoMix 30 combined with acarbose re-duces the amount of insulin when the blood glucose control is at target,and has less incidence of hypoglycemia comparing with four-subcutaneous-insulin injections.

  18. The alpha-amylase inhibitor acarbose does not affect the parasitoid Venturia canescens when incorporated into the diet of its host Ephestia kuehniella

    Kaufnerová, J.; Münzbergová, Zuzana; Jarošík, Vojtěch; Hubert, J.

    2007-01-01

    Roč. 124, č. 1 (2007), s. 17-25. ISSN 0013-8703 R&D Projects: GA ČR(CZ) GA522/04/1286; GA MŠk(CZ) LC06073 Grant ostatní: GA MŠk(CZ) 1P04OC842.20 Institutional research plan: CEZ:AV0Z60050516 Keywords : Ichneumonidae * Lepidoptera * Pyralidae Subject RIV: EF - Botanics Impact factor: 1.483, year: 2007

  19. Drug: D00216 [KEGG MEDICUS

    Full Text Available n hsa04973(279+280+8972) Carbohydrate digestion and absorption map07051 Antidiabetics Therapeutic category o...0BF01 Acarbose D00216 Acarbose (JAN/USAN/INN) USP drug classification [BR:br08302] Blood Glucose Regulators Antidiabetic...ting metabolism 396 Antidiabetic agents 3969 Others D00216 Acarbose (JAN/USAN/INN) Anatomical Therapeutic Ch...f drugs in Japan [BR:br08301] 3 Agents affecting metabolism 39 Other agents affec

  20. alpha-Glycosidase inhibitory activity of hexagalloylglucose from the galls of Quercus infectoria.

    Hwang, J K; Kong, T W; Baek, N I; Pyun, Y R

    2000-04-01

    Hexagalloylglucose (3-O-digalloyl-1,2,4,6-tetra-O-galloyl-beta-D- glucose), which was isolated from the methanol extract of the galls of Quercus infectoria, significantly inhibited alpha-glycosidases such as sucrase, maltase and isomaltase. Its inhibitory activity was comparable to acarbose being used as a hypoglycemic agent, while the inhibitory activity on alpha-amylase was approximately 10 times lower than that of acarbose. The results indicate that, when compared to acarbose, hexagalloylglucose might reduce the side effects by reducing inhibition of alpha-amylase. PMID:10821056

  1. 甘精胰岛素联合阿卡波糖与预混胰岛素治疗2型糖尿病的效果比较%Study on the effects of glargined with acarbose and isophane protamine biosynthetcic human insulin in patients with type 2 diabetic

    李艳萍; 李红梅

    2009-01-01

    目的 比较甘精胰岛素(Glargine)联合阿卡波糖与预混胰岛素(精蛋白生物合成人胰岛素30R)治疗2型糖尿病的疗效及对血糖波动的影响.方法 将65例2型糖尿病随机分为A组采用甘精胰岛素联合阿卡波糖治疗,B组采用预混胰岛素每日2次皮下注射.以空腹血糖(mFBG)<7mmol/L为目标,并监测早餐后2h血糖(mFPIG),午餐后2h血糖(mFP2G)和晚餐后2h血糖(mFP3G)计算1d 4次血糖样本的标准差(SD),以及最高和最低血糖之差(△).观察两组的血糖波动、胰岛素日用量、低血糖发生率.结果 A组胰岛素日用量、低血糖发生率均低于B组(P<0.05),血糖波动小.结论 甘精胰岛素联合阿卡波糖治疗2型糖尿病比预混胰岛素更利于血糖的平稳,低血糖的发生率低,波动影响更小,患者依从性好.

  2. Role of metabolic control on diabetic nephropathy

    Macedo Célia Sperandéo

    2002-01-01

    Full Text Available OBJECTIVE: The aim of this investigation was studying the influence of glucose metabolic control on diabetic nephropathy. The authors observed the effect of acarbose, insulin, and both drugs on the metabolic control and development of mesangial enlargement of kidney glomeruli in alloxan-diabetic rats. METHODS: Five groups of Wistar rats were used: normal rats (N, non-treated alloxan-diabetic rats (D, alloxan-diabetic rats treated with acarbose (AD, alloxan-diabetic rats treated with insulin (ID, and alloxan-diabetic rats treated with insulin plus acarbose (IAD. The following parameters were evaluated: body weight; water and food intake; diuresis; blood and urine glucose levels; and the kidney lesions: mesangial enlargement and tubule cell vacuolization. Renal lesions were analysed using a semi-quantitative score 1, 3, 6, 9, and 12 months after diabetes induction. RESULTS: Diabetic rats showed a marked increase of glycemia, urinary glucose levels, diuresis, water and food intake, and weight loss, while the treated diabetic rats showed significant decreased levels of these parameters. The most satisfactory metabolic control was that of diabetic rats treated with acarbose + insulin. There was a significant mesangial enlargement in diabetic rats compared to normal rats from the third up to the 12th month after diabetes induction, with a significant difference between the animals treated with acarbose + insulin and non-treated diabetic rats. A difference between the animals treated with acarbose or insulin alone and non-treated diabetics rats was not seen. CONCLUSIONS: The authors discuss the results stressing the role of diabetic metabolic control in the prevention of diabetic nephropathy.

  3. Medical management of metabolic dysfunction in PCOS

    Duleba, Antoni J.

    2011-01-01

    Polycystic ovary syndrome (PCOS) is associated with metabolic derangements including insulin resistance, dyslipidemia, systemic inflammation and endothelial dysfunction. There is a growing need to develop pharmacologic interventions to improve metabolic function in women with PCOS. Medications that have been tested in patients with PCOS include metformin, thiazolidinediones, acarbose, naltrexone, orlistat, vitamin D and statins.

  4. 2003~2005年我院口服降糖药物利用分析%Drug utilization analysis of oral hypoglycemic agents in our hospital during the period of 2003 ~ 2005

    辛海莉; 蔡雯雯; 郭蔚

    2007-01-01

    To assess the drug utilization and tendency of progress of oral hypoglycemic agents in our hospital and to provide references for rational administration clinically. Methods: DDDs, sales quantities, sales expenses and the ratio of sales expenses sequencing to that of DDDs in our hospital during the period of 2003 ~ 2005 were analyzed statistically with the method of DDDs analysis. Results:The top two antidiabetic drugs according to DDDs were melbine ( dimethyl diguanide) and gliclazide three successive years. The DDDs of acarbose increased dramatically. Which blood glucose regulatsry drugs ranked lower, the ratio of sales expenses sequencing to that of DDDs of glipizide and gliclazide controlled release pellets was equal or about, whereas that of rosiglitazone, acarbose(glucobay) and glimepiride was less than 1. Conclusion:The study shows that the drug utilization of oral hypoglycemic agents in our hospital is basically rational and is in accordance with the trend of advancement and drug therapeutic strategies of diabetes mellitus.

  5. Antidiabetic potential and secondary metabolites screening of mangrove gastropod Cerithidea obtusa

    Reni Tri Cahyani; Sri Purwaningsih; Azrifitria

    2015-01-01

    Objective: To study the possible effects of Cerithidea obtusa extract as antidiabetic and to screen the secondary metabolites presence. Methods: Antidiabetic activity of Cerithidea obtusa extract was measured in vitro using α-glucosidase inhibition method. Whereas, secondary metabolites screening was measured qualitatively. Results: The methanol extract had antidiabetic activity (IC50 = 36.40 mg/mL). However, the control drug acarbose had significantly higher antidiabetic ac...

  6. In Vitro Screening of Medicinal Plants Used in Mexico as Antidiabetics with Glucosidase and Lipase Inhibitory Activities

    Guillermo Ramírez; Miguel Zavala; Julia Pérez; Alejandro Zamilpa

    2012-01-01

    This work shows the inhibitory effect on glucosidase and lipase enzymes of 23 medicinal plants described as traditional treatments for diabetes in several Mexican sources. Hydroalcoholic extracts of selected plants were evaluated at 1 mg/mL for glucosidase and 0.25 mg/mL for lipase inhibitory activities, respectively. Camellia sinensis, acarbose, and orlistat were used as positive controls. Dose-response curves were done with the most active species. Sixty percent of all tested extracts inhib...

  7. Hyperglykämie bei akutem Myokardsyndrom und operativer Myokardrevaskularisation: Risiken und Management

    Tschöpe D

    2007-01-01

    Full Text Available Ein deutlich erhöhtes periinterventionelles Risiko (PCI und CABG bei Patienten mit Diabetes mellitus Typ 2 kann durch eine normnahe Blutglukoseeinstellung reduziert werden. Die normnahe Blutglukoseeinstellung sollte akut durch Glukose-Insulin-(Kalium- Infusionen (GIK erfolgen. In der Langzeitbetreuung gilt die Zielwerterreichung unabhängig vom pharmakologischen Prinzip der Blutglukosesenkung. Im Spektrum der verfügbaren oralen Antidiabetika scheinen Metformin, Acarbose und Glitazone über pleiotrope Effekte kardioprotektiv zu wirken.

  8. In vitro hypoglycemic effects of selected dietary fiber sources

    Ahmed, Faiyaz; Sairam, Sudha; Urooj, Asna

    2010-01-01

    The physiological functions of dietary fiber and its role in health promotion and risk reduction of some chronic diseases has been well documented. In the present investigation, the effect of three dietary fiber sources, oats (OA), barley (BA) and psyllium husk (PH) on glucose adsorption, diffusion and starch hydrolysis were studied using in vitro techniques by simulating gastrointestinal conditions and compared with the commercial dietary fiber sources wheat bran (WB), acarbose (ACB) and gua...

  9. Inhibition of Porcine Pancreatic Amylase Activity by Sulfamethoxazole: Structural and Functional Aspect.

    Maity, Sujan; Mukherjee, Koel; Banerjee, Amrita; Mukherjee, Suman; Dasgupta, Dipak; Gupta, Suvroma

    2016-06-01

    Combating Type-2 diabetes mellitus is a pivotal challenge in front of the present world. Several lines of therapy are in practice for resisting this deadly disease which often culminates with cardiovascular complexities, neuropathy and retinopathy. Among various therapies, administration of alpha glucosidase inhibitors is common and widely practiced. Sulfonylurea category of anti diabetic drug often suffers from cross reactivity with sulfamethoxazole (SMX), a common drug in use to treat a handful of microbial infections. However the specific cellular target generating postprandial hypoglycemia on SMX administration is till date unraveled. The present work has been initiated to elucidate the effects of a group of sulfonamide drugs inclusive of SMX for their amylase inhibitory role. SMX inhibits porcine pancreatic amylase (PPA) in a noncompetitive mode with an average IC50 value 0.94 mM respectively. Interaction of SMX with PPA is manifested with gradual quenching of tryptophan fluorescence with concomitant shift in lambda max value (λmax). Binding is governed by entropy driven factor (24.8 cal mol(-1) K(-1)) with unfavorable contribution from enthalpy change. SMX interferes with the activity of acarbose in a synergistic mode to reduce the effective dose of acarbose as evident from the in vitro PPA inhibition study. In summary, loss of PPA activity in presence of SMX is indicative of structural changes of PPA which is further augmented in the presence of acarbose as explained in the schematic model and docking study. PMID:27272220

  10. Glucose lowering effect of montbretin A in Zucker Diabetic Fatty rats.

    Yuen, Violet G; Coleman, John; Withers, Steven G; Andersen, Raymond J; Brayer, Gary D; Mustafa, Sally; McNeill, John H

    2016-01-01

    Diabetes is an increasingly prevalent disease state with a global impact. It is important that effective and cost-efficient methods be developed to treat this disease state. Zucker diabetic fatty rats, an animal model of type 2 diabetes, were treated with montbretin A (MbA), a selective human pancreatic α-amylase inhibitor, isolated from the corms of the Crocosmia crocosmiiflora plant that may have potential as a glucose-lowering agent. The study purpose was to determine if MbA was an orally effective treatment for diabetes. The effect of MbA was compared to a current clinical treatment modality, acarbose that is associated with gastrointestinal side effects known to affect patient compliance. MbA and acarbose were administered daily in the drinking water. Body weight and fluid intake were measured daily to calculate dose consumption. Plasma glucose levels were determined twice weekly in both the fed and fasted state. At termination samples were collected to assess increased risk of secondary complications related to diabetes and oxidative stress. There was no effect of either MbA or acarbose treatment on insulin levels. Plasma glucose levels were significantly lower following MbA treatment in the ZT group which persisted throughout the study period (day 49: 12.1 ± 1.2 mM). However, while there was an initial decrease in plasma glucose levels in the acarbose-treated fatty group, this effect was not sustained (day 49: 20.6 ± 1.3 mM) through to termination. MbA improved the oxidative status of the fatty diabetic animals as well as attenuated markers for increased risk of cardiovascular complications associated with diabetes. This study demonstrated that, at a lower dose as compared to acarbose (10 mg/kg/day), chronic oral administration of MbA (7.5 mg/kg/day) was an effective glucose-lowering agent in the treatment of type 2 diabetes. PMID:26547551

  11. Characterization of a Digestive α-Amylase in the Midgut of Pieris brassicae L. (Lepidoptera: Pieridae).

    Sharifloo, Ali; Zibaee, Arash; Sendi, Jalal J; Jahroumi, Khalil Talebi

    2016-01-01

    The current study deals with a digestive α-amylase in the larvae of Pieris brassicae L. through purification, enzymatic characterization, gene expression, and in vivo effect of a specific inhibitor, Acarbose. Although α-amylase activity was the highest in the whole gut homogenate of larvae but compartmentalization of amylolytic activity showed an equal activity in posterior midgut (PM) and anterior midgut (AM). A three step purification using ammonium sulfate, Sepharyl G-100 and DEAE-Cellulose Fast flow revealed an enzyme with a specific activity of 5.18 U/mg, recovery of 13.20, purification fold of 19.25 and molecular weight of 88 kDa. The purified α-amylase had the highest activity at optimal pH and temperature of 8 and 35°C. Also, the enzyme had V max values of 4.64 and 3.02 U/mg protein and K m values of 1.37 and 1.74% using starch and glycogen as substrates, respectively. Different concentrations of acarbose, ethylenediamine tetraacetic acid, and ethylene glycol-bis (β-aminoethylether) N, N, N', N'-tetraacetic acid significantly decreased activity of the purified α-amylase. The 4th instar larvae of P. brassicae were fed on the treated leaves of Raphanus sativus L. with 0.22 mM of Acarbose to find in vivo effects on nutritional indices, α-amylase activity, and gene expression. The significant differences were only found in conversion efficiency of digested food, relative growth rate, and metabolic cost of control and fed larvae on Acarbose. Also, amylolytic activity significantly decreased in the treated larvae by both biochemical and native-PAGE experiments. Results of RT-PCR revealed a gene with 621 bp length responsible for α-amylase expression that had 75% identity with Papilio xuthus and P. polytes. Finally, qRT-PCR revealed higher expression of α-amylase in control larvae compared to acarbose-fed ones. PMID:27014094

  12. Characterization of a Digestive α-Amylase in the Midgut of Pieris brassicae L. (Lepidoptera: Pieridae)

    Sharifloo, Ali; Zibaee, Arash; Sendi, Jalal J.; Jahroumi, Khalil Talebi

    2016-01-01

    The current study deals with a digestive α-amylase in the larvae of Pieris brassicae L. through purification, enzymatic characterization, gene expression, and in vivo effect of a specific inhibitor, Acarbose. Although α-amylase activity was the highest in the whole gut homogenate of larvae but compartmentalization of amylolytic activity showed an equal activity in posterior midgut (PM) and anterior midgut (AM). A three step purification using ammonium sulfate, Sepharyl G-100 and DEAE-Cellulose Fast flow revealed an enzyme with a specific activity of 5.18 U/mg, recovery of 13.20, purification fold of 19.25 and molecular weight of 88 kDa. The purified α-amylase had the highest activity at optimal pH and temperature of 8 and 35°C. Also, the enzyme had Vmax values of 4.64 and 3.02 U/mg protein and Km values of 1.37 and 1.74% using starch and glycogen as substrates, respectively. Different concentrations of acarbose, ethylenediamine tetraacetic acid, and ethylene glycol-bis (β-aminoethylether) N, N, N′, N′-tetraacetic acid significantly decreased activity of the purified α-amylase. The 4th instar larvae of P. brassicae were fed on the treated leaves of Raphanus sativus L. with 0.22 mM of Acarbose to find in vivo effects on nutritional indices, α-amylase activity, and gene expression. The significant differences were only found in conversion efficiency of digested food, relative growth rate, and metabolic cost of control and fed larvae on Acarbose. Also, amylolytic activity significantly decreased in the treated larvae by both biochemical and native-PAGE experiments. Results of RT-PCR revealed a gene with 621 bp length responsible for α-amylase expression that had 75% identity with Papilio xuthus and P. polytes. Finally, qRT-PCR revealed higher expression of α-amylase in control larvae compared to acarbose-fed ones. PMID:27014094

  13. Genetic engineering in Actinoplanes sp. SE50/110 - development of an intergeneric conjugation system for the introduction of actinophage-based integrative vectors.

    Gren, Tetiana; Ortseifen, Vera; Wibberg, Daniel; Schneiker-Bekel, Susanne; Bednarz, Hanna; Niehaus, Karsten; Zemke, Till; Persicke, Marcus; Pühler, Alfred; Kalinowski, Jörn

    2016-08-20

    The α-glucosidase inhibitor acarbose is used for treatment of diabetes mellitus type II, and is manufactured industrially with overproducing derivatives of Actinoplanes sp. SE50/110, reportedly obtained by conventional mutagenesis. Despite of high industrial significance, only limited information exists regarding acarbose metabolism, function and regulation of these processes, due to the absence of proper genetic engineering methods and tools developed for this strain. Here, a basic toolkit for genetic engineering of Actinoplanes sp. SE50/110 was developed, comprising a standardized protocol for a DNA transfer through Escherichia coli-Actinoplanes intergeneric conjugation and applied for the transfer of ϕC31, ϕBT1 and VWB actinophage-based integrative vectors. Integration sites, occurring once per genome for all vectors, were sequenced and characterized for the first time in Actinoplanes sp. SE50/110. Notably, in case of ϕC31 based vector pSET152, the integration site is highly conserved, while for ϕBT1 and the VWB based vectors pRT801 and pSOK804, respectively, no sequence similarities to those in other bacteria were detected. The studied plasmids were proven to be stable and neutral with respect to strain morphology and acarbose production, enabling future use for genetic manipulations of Actinoplanes sp. SE50/110. To further broaden the spectrum of available tools, a GUS reporter system, based on the pSET152 derived vector, was also established in Actinoplanes sp. SE50/110. PMID:27181842

  14. Alpha-amylase inhibitory activity and phytochemical study of Zhumeria majdae Rech. f. and Wendelbo

    Behnaz Mirshafie

    2015-01-01

    Full Text Available Background: Zhumeria majdae (Lamiaceae is an endemic species growing in the South parts of Iran especially Hormozgan province. The plant is so-called Mohrekhosh locally and widely used for medicinal purposes including stomachache and dysmenorrhea. Objective: In order to separation and identification of the main flavonoid glycosides of the plant (aerial parts including leaves, stems, flowers, and fruits were used and evaluation of its alpha-amylase inhibitory (AAI activity, methanolic extract was prepared and fractionated to botanolic portion. Materials and Methods: Isolation of the main compounds of the butanol extract of the plant have been performed using different column chromatography methods such as high-performance liquid chromatography (C 18 column and Sephadex LH-20 as well. The isolated compounds were identified by Hydrogen-1 nuclear magnetic resonance and Carbon-13 nuclear magnetic resonance spectra and comparison with those reported in previous literature. Moreover, inhibitory activity of the butanolic extract of the plant against alpha-amylase enzyme was examined in different concentrations (15-30 mg/mL, where acarbose used as a positive control. Results: Three flavonoid glycosides: Linarin (1, hispidulin-7-O-(4-O-acetyl-rutinoside (2, hispidulin-7-O-rutinoside (3 were successfully identified in the extract. The activity of alpha amylase enzyme was dose-dependently suppressed by the butanol extract. The extract exhibited the highest inhibition at 30 mg/mL toward enzyme (77.9 ± 2.1%, while acarbose inhibited the enzyme at 20 mg/mL by 73.9 ± 1.9%. The inhibitory concentrations of 50% for the extract and acarbose were calculated at 24.5 ± 2.1 and 6.6 ± 3.1 mg/mL, respectively. Conclusion: Z. majdae contains glycosylated flavones and could be a good candidate for anti-diabetic evaluations in animal and clinical trials due to possessing AAI activity.

  15. The 53-kDa proteolytic product of precursor starch-hydrolyzing enzyme of Aspergillus niger has Taka-amylase-like activity.

    Ravi-Kumar, K; Venkatesh, K S; Umesh-Kumar, S

    2007-04-01

    The 53-kDa amylase secreted by Aspergillus niger due to proteolytic processing of the precursor starch-hydrolyzing enzyme was resistant to acarbose, a potent alpha-glucosidase inhibitor. The enzyme production was induced when A. niger was grown in starch medium containing the inhibitor. Antibodies against the precursor enzyme cross-reacted with the 54-kDa Taka-amylase protein of A. oryzae. It resembled Taka-amylase in most of its properties and also hydrolyzed starch to maltose of alpha-anomeric configuration. However, it did not degrade maltotriose formed during the reaction and was not inhibited by zinc ions. PMID:17123073

  16. Identification of Highly Potent and Selective α-Glucosidase Inhibitors with Antiglycation Potential, Isolated from Rhododendron arboreum

    Rabia Raza; Zaitoon Ilyas; Sajid Ali; Muhammad Nisar; Muhammad Younas Khokhar; Jamshed Iqbal

    2015-01-01

    This study explored antidiabetic potential of eight known pure compounds, isolated from the bark of Rhododendron arboreum. Invitro studies of these compounds against α and β-glucosidases revealed them as very potent and selective inhibitors of α-glucosidase. Compound 7 (3-O-acetylursolic acid) was found to be the most potent inhibitor of α-glucosidase with 3.3±0.1µM IC 50 value which was many folds higher than standard inhibitor acarbose. Antiglycation studies of compounds showed that all com...

  17. Antidiabetic potential and secondary metabolites screening of mangrove gastropod Cerithidea obtusa

    Reni Tri Cahyani; Sri Purwaningsih; Azrifitria

    2015-01-01

    Objective: To study the possible effects of Cerithidea obtusa extract as antidiabetic and to screen the secondary metabolites presence. Methods: Antidiabetic activity of Cerithidea obtusa extract was measured in vitro usingα-glucosidase inhibition method. Whereas, secondary metabolites screening was measured qualitatively. Results: The methanol extract had antidiabetic activity (IC50 = 36.40 mg/mL). However, the control drug acarbose had significantly higher antidiabetic activity (IC50 = 0.32 mg/mL). Secondary metabolites screening showed the presence of alkaloids, flavonoids, triterpenoids and saponins. Conclusions: The methanol extract had antidiabetic activity and the presence of alkaloids, flavonoids and triterpenoids might contribute to the activity.

  18. Effects of diet, sulphonylurea group of oral antidiabetic drugs and insülin treatment on blood glucose levels in patients with Type 2 diabetes mell tus

    BÜYÜKBERBER, Dr. Y. Furkan ÇAĞIN Dr. Haluk ŞAVLI Dr

    1999-01-01

    In this randomized prospective study, we investigated the effects of diet, gliclazide, gliclazide and acarbose and insulin on blood glucose levels of Type 2 diabetic patients. Sixty-four patients, 30 males (12 obese and 18 non-obese) and 34 females (20 obese and 14 non-obese), aged 50.83±6.88 years (range 36-66) with a fasting blood glucose level of 140 to 270 mg/dL zere included. Patients were divided into two groups (obese and nonobese) before randomization and both groups were d...

  19. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin

    Arumugam Madeswaran; Kuppusamy Asokkumar; Muthuswamy Umamaheswari; Thirumalaisamy Sivashanmugam; Varadharajan Subhadradevi

    2014-01-01

    Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selec...

  20. Traditionally used plants in diabetes therapy: phytotherapeutics as inhibitors of alpha-amylase activity Plantas tradicionalmente utilizadas na terapia da diabetes: fitomedicamentos como inibidores da atividade alfa-amilase

    Ingrid Funke

    2006-03-01

    Full Text Available Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycaemia. There are many and diverse therapeutic strategies in the management of Type 2 diabetes. The inhibition of alpha-amylase activity is only one possibility to lower postprandial blood glucose levels. In our in-vitro studies we could demonstrate that different plants, mostly traditionally used in common diabetic therapy in Africa or Europe, are able to inhibit alpha-amylase, which is responsible for the breakdown of oligosaccharides into monosaccharides which are absorbed. An inhibition of alpha-amylase activity of 90% was seen with the extract of the leaves of Tamarindus indica. To quantify inhibtion rates, acarbose was used (IC50: 23.2 µM. Highest inhibition level of acarbose in our testmodel was about 85%. Additionally tests with pure polyphenolic compounds might explain the biological activity of the selected plants.Diabetes mellitus é uma desordem metabólica caracterizada pela hiperglicemia crônica. Existem diversas estratégias terapêuticas no tratamento da diabetes Tipo 2. A inibição da atividade da a-amilase é apenas uma possibilidade de reduzir os níveis de glicose posprandiais. Nos nossos estudos in vitro pudemos demonstrar que diferentes plantas, especialmente as tradicionalmente usadas em terapia comum de diabetes na África ou Europa, são capazes de inibir a a-amilase, a qual é responsável pela quebra dos oligossacarídeos em monossacarídeos, os quais são absorvidos. Uma inibição da atividade da a-amilase da ordem de 90% foi observada com o extrato das folhas de Tamarindus indica. Para quantificar os graus de inibição, acarbose foi usada (IC50: 23,2 mM. O maior grau de inibição de acarbose no nosso modelo de teste foi de cerca de 85%. Adicionalmente testes com compostos polifenólicos puros poderão explicar a atividade biológica das plantas selecionadas.

  1. Traditional Medicinal Herbs and Food Plants Have the Potential to Inhibit Key Carbohydrate Hydrolyzing Enzymes In Vitro and Reduce Postprandial Blood Glucose Peaks In Vivo

    M. Fawzi Mahomoodally

    2012-01-01

    Full Text Available We hypothesized that some medicinal herbs and food plants commonly used in the management of diabetes can reduce glucose peaks by inhibiting key carbohydrate hydrolyzing enzymes. To this effect, extracts of Antidesma madagascariense (AM, Erythroxylum macrocarpum (EM, Pittosporum senacia (PS, and Faujasiopsis flexuosa (FF, Momordica charantia (MC, and Ocimum tenuiflorum (OT were evaluated for α-amylase and α-glucosidase inhibitory effects based on starch-iodine colour changes and PNP-G as substrate, respectively. Only FF and AM extracts/fractions were found to inhibit α-amylase activity significantly (P<0.05 and coparable to the drug acarbose. Amylase bioassay on isolated mouse plasma confirmed the inhibitory potential of AM and FF extracts with the ethyl acetate fraction of FF being more potent (P<0.05 than acarbose. Extracts/fractions of AM and MC were found to inhibit significantly (P<0.05 α-glucosidase activity, with IC50 comparable to the drug 1-deoxynojirimycin. In vivo studies on glycogen-loaded mice showed significant (P<0.05 depressive effect on elevation of postprandial blood glucose following ingestion of AM and MC extracts. Our findings tend to provide a possible explanation for the hypoglycemic action of MC fruits and AM leaf extracts as alternative nutritional therapy in the management of diabetes.

  2. Triterpenes as uncompetitive inhibitors of α-glucosidase from flowers of Punica granatum L.

    Salah El Dine, Riham; Ma, Qiong; Kandil, Zeinab A; El-Halawany, Ali M

    2014-01-01

    The α-glucosidase and maltase inhibitory effects of Punica granatum L. flowers (PGF) were investigated. The methanol extract (PGFMe), n-hexane extract (PGFH), chloroform extract (PGFC) and the remaining water fraction (PGFW) were assayed for their α-glucosidase and maltase inhibitory effects. PGFW showed potent α-glucosidase inhibition with IC₅₀ of 0.8 μg/mL followed by PGFMe (IC₅₀ of 4.0 μg/mL) then PGFC (IC₅₀ of 5.21 μg/mL) in comparison to acarbose (0.9 μM). Due to its selectivity towards α-glucosidase, PGFC was subjected to bioactivity-guided isolation of its main active constituents. Five known compounds (1-5) were identified as β-sitosterol (1), oleanolic acid (2), ursolic acid (3), p-coumaric acid (4) and apigenin (5). Ursolic and oleanolic acids showed potent α-glucosidase inhibition (IC₅₀ of 39.0 and 35.0 μM, respectively), while they did not show significant maltase inhibition. Kinetic study using the double Lineweaver-Burk plot revealed that ursolic acid uncompetitively inhibited α-glucosidase in comparison with acarbose as a competitive inhibitor. PMID:24956202

  3. Aqueous Extract of Nypa fruticans Wurmb. Vinegar Alleviates Postprandial Hyperglycemia in Normoglycemic Rats

    Nor Adlin Yusoff

    2015-08-01

    Full Text Available Nypa fruticans Wurmb. vinegar, commonly known as nipa palm vinegar (NPV has been used as a folklore medicine among the Malay community to treat diabetes. Early work has shown that aqueous extract (AE of NPV exerts a potent antihyperglycemic effect. Thus, this study is conducted to evaluate the effect of AE on postprandial hyperglycemia in an attempt to understand its mechanism of antidiabetic action. AE were tested via in vitro intestinal glucose absorption, in vivo carbohydrate tolerance tests and spectrophotometric enzyme inhibition assays. One mg/mL of AE showed a comparable outcome to the use of phloridzin (1 mM in vitro as it delayed glucose absorption through isolated rat jejunum more effectively than acarbose (1 mg/mL. Further in vivo confirmatory tests showed AE (500 mg/kg to cause a significant suppression in postprandial hyperglycemia 30 min following respective glucose (2 g/kg, sucrose (4 g/kg and starch (3 g/kg loadings in normal rats, compared to the control group. Conversely, in spectrophotometric enzymatic assays, AE showed rather a weak inhibitory activity against both α-glucosidase and α-amylase when compared with acarbose. The findings suggested that NPV exerts its anti-diabetic effect by delaying carbohydrate absorption from the small intestine through selective inhibition of intestinal glucose transporters, therefore suppressing postprandial hyperglycemia.

  4. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico.

    Jhong, Chien-Hung; Riyaphan, Jirawat; Lin, Shih-Hung; Chia, Yi-Chen; Weng, Ching-Feng

    2015-01-01

    The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants. PMID:26154585

  5. Inhibitory potential of Grifola frondosa bioactive fractions on α-amylase and α-glucosidase for management of hyperglycemia.

    Su, Chun-Han; Lu, Tzy-Ming; Lai, Min-Nan; Ng, Lean-Teik

    2013-01-01

    This study examined the inhibitory effects of Grifola frondosa (GF), a medicinal mushroom popularly consumed in traditional medicine and health food, on digestive enzymes related to type 2 diabetes; chemical profiles and inhibitory kinetics of its bioactive fractions were also analyzed. Results showed that all GF extracts showed weak anti-α-amylase activity; however, strong anti-α-glucosidase activity was noted on GF n-hexane extract (GF-H). Further fractionation confirmed that compared with acarbose (a commercial α-glucosidase inhibitor), the nonpolar fraction of GF possessed a stronger anti-α-glucosidase activity but a weaker anti-α-amylase activity. These activities were not derived from ergosterol and ergosterol peroxide, two major compounds of this fraction. The inhibitory kinetics of GF-H on α-glucosidase was competitive inhibition. GF-H was as good as acarbose in inhibiting the starch digestion in vitro. Oleic acid and linoleic acid could be the major active constituents that have contributed to the potency of GF in inhibiting α-glucosidase activity. PMID:24033596

  6. Inhibition of α-glucosidase activity by ethanolic extract of Melia azedarach L. leaves

    Sulistiyani; Safithri, Mega; Puspita Sari, Yoana

    2016-01-01

    Development of α-glucosidase inhibitor derived from natural products is an opportunity for a more economic management of diabetes prevention. The objective of this study was to test the activity of α-glucosidase with or without potential inhibitor compounds. By in vitro method, α-glucosidase hydrolizes p-nitrophenyl-α-D-glucopiranoside to glucose and the yellow of p-nitrophenol which can be determined with spectrophotometry at 400 nm. The ability of ethanolic leaf extract of Melia azedarach L. as a-glucosidase inhibitor was compared with that of commercial acarbose (Glucobay®). Acarbose showed strong inhibitory activity against a-glucosidase with IC50 values of 2.154 µg/mL. The crude ethanolic leaf extract of M. azedarach, however, showed less inhibitory activity with IC50 value of 3, 444.114 µg/mL. Total phenolics of M. azedarach leaves EtOH extract showed 17.94 µg GAE/mg extract and flavonoids total compound of 9.55 µg QE/mg extract. Based on the published wide range of IC50 values of extracts reported as a-glucosidase inhibitor which were between 10, 000 ppm-0.66 ppm, our result suggests that extract of M.azedarach leaves is potential candidate for development of anti-hyperglycemic formulation.

  7. 2011~2012我院门诊患者口服降血糖药物应用分析%2011-2012 in Our Hospital Outpatients Oral Fall Blood Sugar Medicine Application Analysis

    胡廷雪

    2013-01-01

    目的了解我院门诊患者口服降糖药应用情况,指导临床合适用药。方法统计2011年~2012年2年内门诊患者口服降糖药物的应用情况,统计内容包括口服降糖药物的名称、规格、销售数量、销售金额、限定日剂量、用药频度以及日用药金额等。结果口服降糖药中的阿卡波糖、二甲双胍以及瑞格列奈药物的销售额连续2年均位居前3位,二甲双胍、阿卡波糖和格列吡嗪药物使用频度较高,连续2年均保持着前3位,从DDDc来看,阿卡波糖和瑞格列奈最高,而吡格列酮和二甲双胍最低,销售金额序号与DDDs序号的比值在0.33~2.00之间。结论我院口服降糖药的应用基本科学、合理、有效,符合用药的基本原则。%Objective To understand the application of oral hypoglycemic drugs in our hospital outpatient patients, guiding clinical proper medication. Methods Statistics from 2011 to 2012,2 years outpatient oral hypoglycemic drugs, statistics includes name, oral antidiabetic drug specifications, sales volume, sales amount, defined daily dose, DDDs and daily cost.Results The oral hypoglycemic drugs acarbose, metformin and repaglinide drug sales for 2 consecutive years ranked the top 3, the higher frequency of metformin, acarbose and glipizide drug use, for 2 consecutive years maintained the top 3, from DDDc, acarbose, repaglinide column Nai the highest and lowest, pioglitazone and metformin, sales the amount of numbers and the DDDs numbers of the ratio between 0.33 and 2.Conclusion Oral hypoglycemic drugs in our hospital in basic science, application of reasonable, effective, consistent with the fundamental principles of drug.

  8. Marrubiin: a potent α-glucosidase inhibitor from Marrubium alysson.

    M. Abd El-Mohsen

    2014-02-01

    Full Text Available Summary. α-Glucosidase is an important target to discover new agents for treatment of diabetes-II and in slimming. The objective of this study is to investigate the effect of marrubiin, a major constituent of many medicinal plants including Marrubium alysson, as α-Glucosidase inhibitor. Bioassay-guided screening, isolation and purification of bioactive compounds of methanol extract of M. alysson was carried out followed by identification using 1H and 13C NMR analysis, and comparing isolated compounds with the published data. Inhibition of α-glucosidase activity bioassay at different concentrations of enzyme (0.3, 0.6, 1.5, 3 and 6 U/ml and substrate (sucrose: 7.5, 15, 30, 60 and 120 mM, and at different pretreatment times. Alpha-acarbose used as positive control in comparison to isolated compounds. Molecular docking was done to find out the interaction between compounds and the α-glucosidase receptor using MOE (molecular modeling environment. Bioassay-guided isolation led to the identification of three known labdane diterpenes; from which marrubiin (1 showed strong inhibition with IC50 of 16.62 μM. Docking studies of compound (1 against the α-glucosidase enzyme gave comparable scores and hydrogen bond interaction (-12.474 kcal/mol but different binding mode to the alpha-acarbose (-12.335 kcal/mol. These data suggest that marrubiin has an inhibitory effect on α-glucosidase activity and these findings provide insight into the traditional uses of Marrubium species for treatment of diabetes. Industrial relevance. Natural products isolated from plants are rich source to new drugs for medicinal use. Docking studies of marrubiin diterpenes against the α-glucosidase enzyme gave comparable scores and hydrogen bond interaction but different binding mode to the positive standard alpha-acarbose. These data suggest that marrubiin has an inhibitory effect on α-glucosidase activity and these findings provide insight into the traditional uses of

  9. Identification of Highly Potent and Selective α-Glucosidase Inhibitors with Antiglycation Potential, Isolated from Rhododendron arboreum

    Rabia Raza

    2015-01-01

    Full Text Available This study explored antidiabetic potential of eight known pure compounds, isolated from the bark of Rhododendron arboreum. Invitro studies of these compounds against α and β-glucosidases revealed them as very potent and selective inhibitors of α-glucosidase. Compound 7 (3-O-acetylursolic acid was found to be the most potent inhibitor of α-glucosidase with 3.3±0.1µM IC 50 value which was many folds higher than standard inhibitor acarbose. Antiglycation studies of compounds showed that all compounds were also very active antiglycation agents. The studied biological properties of these compounds suggest that they are therapeutically interesting and important tools for treatment of diabetes.

  10. Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus.

    Ying, You-Min; Zhang, Lin-Yan; Zhang, Xia; Bai, Hai-Bo; Liang, Dong-E; Ma, Lie-Feng; Shan, Wei-Guang; Zhan, Zha-Jun

    2014-12-01

    Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus. PMID:25446238

  11. PENGHAMBAT α AMILASE: JENIS, SUMBER, DAN POTENSI PEMANFAATANNYA DALAM KESEHATAN [α Amylase Inhibitors: Types, Sources, and Their Potential Utilization for Health Purposes

    Budiasih Wahyuntari

    2011-12-01

    Full Text Available SUMMARYAlpha amylase inhibitors affect carbohydrate metabolism in digestive system. The inhibitors induce carbohydrate tolerance, fullness and prolonging gastric emptying that might be used to aid in diabetic and obesity treatment. There are two types of α- amylase inhibitors, proteinaceous and non-proteinaceous ones. Proteinaceous inhibitor is classified into seven classes including legumes, lectin, knottin, cereal, Kunitz, -thionin and thaumatin types. Plant proteinaceous inhibitors are present in cereals and legumes. Some non-proteinaceous inhibitors include flavonid, polyphenols, organic acid that might be produced by microbes or extracted from plants such as acarbose, saponin dan cardiac glycoside, gallic acid, proto-catechuic acid, caffeic acid, ellagic acid, ferulic acid, quercetin hibiscus acid and α-, β- and γ-cyclodextrin.

  12. Oligosaccharide binding to barley alpha-amylase 1

    Robert, X.; Haser, R.; Mori, H.; Svensson, Birte; Aghajari, N.

    2005-01-01

    insight into the substrate binding by describing residues defining 9 subsites, namely -7 through +2. These structures support that the pseudotetrasaccharide inhibitor acarbose is hydrolyzed by the active enzymes. Moreover, sugar binding was observed to the starch granule-binding site previously determined...... in barley alpha-amylase isozyme 2 (AMY2), and the sugar binding modes are compared between the two isozymes. The "sugar tongs" surface binding site discovered in the AMY1-thio-DP4 complex is confirmed in the present work. A site that putatively serves as an entrance for the substrate to the active...... active site for polysaccharide chains. Moreover, the sugar tongs surface site could also perform the unraveling of amylose chains, with the aid of Tyr-380 acting as "molecular tweezers"....

  13. Nutritional Composition, α-Glucosidase Inhibitory and Antioxidant Activities of Ophiopogon japonicus Tubers

    Yancui Wang

    2015-01-01

    Full Text Available Ophiopogon japonicus tubers have been widely used as food and traditional Chinese medicine in China. However, their nutritional composition has not been fully reported yet. This study aimed to analyze the nutritional composition of O. japonicus tubers. The α-glucosidase inhibitory and antioxidant activities of the extracts obtained from O. japonicus tubers were also evaluated by in vitro assays. The results indicated that O. japonicus tubers are rich in carbohydrates, proteins, minerals, and amino acids. Among four extracts, the n-butanol fraction (nBF and chloroform/methanol extract (CME of O. japonicus tubers had high amounts of total phenolic and flavonoid contents and exhibited good α-glucosidase inhibitory and antioxidant activities. The α-glucosidase inhibition of nBF was higher than acarbose. Overall, O. japonicus tubers are full of nutritional compounds and have good α-glucosidase inhibitory and antioxidant activities.

  14. α-GLUCOSIDASE AND α -AMYLASE INHIBITORY ACTIVITIES OF RAPHANUS SATIVUS LINN.

    R. Vadivelan et al

    2012-09-01

    Full Text Available Herbal medicine has been used for many years by different cultures around the world for the treatment of diabetes. There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study is to evaluate the invitro antidiabetic activity of Raphanus sativus ethanolic extract and fractions by α-glucosidase and α -amylase inhibitory activity. Raphanus sativus ethanolic extract and fractions showed dose dependent inhibition of α-glucosidase and α -amylase enzyme and exhibited lower inhibitory activity than acarbose. The study revealed the antidiabetic potential and could be helpful to develop medicinal preparations and nutraceuticals and function foods for diabetes.

  15. Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity

    Cui, Hui; Liu, Yayue; Nie, Yang; Liu, Zhaoming; Chen, Senhua; Zhang, Zhengrui; Lu, Yongjun; He, Lei; Huang, Xishan; She, Zhigang

    2016-01-01

    Four new polyketides: nectriacids A–C (1–3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher’s ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC50 values of 23.5 and 42.3 μM, respectively, which were more potent than positive control (acarbose, IC50, 815.3 μM). PMID:27136568

  16. In Vitro Antioxidant and Enzymes Inhibitory activity of Chloroform Fraction of Hydroalcoholic extract obtained from Argemone mexicana

    Nayak P

    2013-03-01

    Full Text Available In the present investigation antioxidant and alphaamylase inhibitory activity of chloroform fraction of Argemone mexicana were evaluated. The antioxidant activity of chloroform fraction of A. mexicana was evaluated by DPPH, Super oxide radical Scavenging activity, ABTS radical cation scavenging activity and Nitric oxide radical scavenging activity. Alpha-amylase inhibitory activity of chloroform fraction was evaluated by DNS method respectively. The observed resultant antioxidant activity of chloroform fraction in all studied models was moderate as compared with reference standard Ascorbic acid. The chloroform fraction exhibited appreciable α-amylase inhibitory activity with an IC50 value 48.92μg/ml respectively, when compared with acarbose (IC50 value 83.33μg/ml.In conclusion, from the results of present study it is confirmed that antioxidant and alpha-amylase inhibitory activity of chloroform fraction of A. mexicana may contribute in its earlier observed antidiabetic potential.

  17. Synthesis and Evaluation of a Series of Oleanolic Acid Saponins as α-Glucosidase and α-Amylase Inhibitors.

    Guo, Tiantian; Wu, Shaoping; Guo, Sen; Bai, Lu; Liu, Qingchao; Bai, Naisheng

    2015-09-01

    Sixteen naturally occurring oleanolic acid saponins and their derivatives were synthesized in an efficient and practical strategy, and their inhibitory activities against α-glucosidase and α-amylase were evaluated in vitro. Among all the compounds, 28-O-monoglucoside 8 exhibited remarkably potent inhibitory activity against α-glucosidase with an IC50 value of 87.3 µM, which was fivefold stronger than that of the antidiabetic acarbose. Based on the preliminary structure-activity relationships, for 28-O-monoglucosides, the presence of a terminal α-l-rhamnopyranosyl residue enhanced the α-glucosidase and α-amylase inhibitory activities. Furthermore, for 3,28-O-bidesmosides, sugar-substituted moieties attached to the C-3 and C-28 positions of the oleanolic acid scaffold are helpful to increase the inhibitory activities against α-amylase and α-glucosidase. PMID:26207761

  18. Insights into the "pair of sugar tongs" surface binding site in barley alpha-amylase isozymes and crystallization of appropriate sugar tongs mutants

    Tranier, S.; Deville, K.; Robert, X.; Bozonnet, Sophie; Haser, R.; Svensson, Birte; Aghajari, N.

    2005-01-01

    additional surface binding site called a "pair of sugar tongs" due to the sugar capturing by Tyr380 which is situated in domain C of AMYL For the first time, a biological role for the domain C was suggested as well as a hypothetical explanation of enzymatic differences between the two barley a...... mutational engineering. Also, the contribution of domain A could be suggested in addition to minor differences implying interacting residues at the "sugar tongs" binding site. Finally, the successful crystallization of five mutants in the "sugar tongs" binding site is reported.......-amylase isozymes. However, no sugar was bound at the "sugar tongs" site in the AMY2/acarbose complex. Comparative studies of this domain on the basis of sequence, secondary structure and spatial organization allow to propose factors needed for such a site. One of the most obvious is the replacement of Ser378(AMY1...

  19. From carbohydrates to drug-like fragments: Rational development of novel α-amylase inhibitors.

    Al-Asri, Jamil; Fazekas, Erika; Lehoczki, Gábor; Perdih, Andrej; Görick, Cornelia; Melzig, Matthias F; Gyémánt, Gyöngyi; Wolber, Gerhard; Mortier, Jérémie

    2015-10-15

    Starch catabolism leading to high glucose level in blood is highly problematic in chronic metabolic diseases, such as type II diabetes and obesity. α-Amylase catalyzes the hydrolysis of starch, increasing blood sugar concentration. Its inhibition represents a promising therapeutic approach to control hyperglycaemia. However, only few drug-like molecule inhibitors without sugar moieties have been discovered so far, and little information on the enzymatic mechanism is available. This work aims at the discovery of novel small α-amylase binders using a systematic in silico methodology. 3D-pharmacophore-based high throughput virtual screening of small compounds libraries was performed to identify compounds with high α-amylase affinity. Twenty-seven compounds were selected and biologically tested, revealing IC50 values in the micromolar range and ligand efficiency higher than the one of the bound form of acarbose, which is used as a reference for α-amylase inhibition. PMID:26395057

  20. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles.

    Taha, Muhammad; Ismail, Nor Hadiani; Imran, Syahrul; Wadood, Abdul; Rahim, Fazal; Saad, Syed Muhammad; Khan, Khalid Mohammed; Nasir, Abdul

    2016-06-01

    Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction. PMID:27149363

  1. Report: screening of selected medicinal plants for their enzyme inhibitory potential - a validation of their ethnopharmacological uses.

    Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Shah, Yasar; Khan, Abad

    2014-05-01

    In present study four medicinal plants namely Valeriana wallichii, Xanthium strumarium, Achyranthes aspera and Duchesnea indica belonging to different families were collected in Khyber Pakhtunkhwa province and crude extract and subsequent fractions were analyzed for their inhibitory potential against acetylcholinesterase, butyrylcholinesterase and α-glucosidase enzymes. Valeriana wallichii, Xanthium strumarium and Achyranthes aspera were significantly active against cholinesterases. Chloroform and ethylacetate fractions of Valeriana wallichii exhibited significant activity against acetylcholinesterase (IC50: 61μg/ml) and butyrylcholinesterase enzymes (IC50: 58μg/ml), respectively. Similarly ethylacetate fraction of Achyranthes aspera showed significant activity against acetylcholinesterase (IC50: 61 μg/ml) and butyrylcholinesterase enzymes (IC50: 61 μg/ml), respectively. In case of α-glucosidase enzyme, the chloroform fraction of Xanthium strumarium exhibited significant inhibitory activity (IC50: 72 μg/ml) as compared to the standard compound acarbose (IC50: 483 μg/ml). Duchesnea indica showed no such activities. PMID:24811822

  2. Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity.

    Cui, Hui; Liu, Yayue; Nie, Yang; Liu, Zhaoming; Chen, Senhua; Zhang, Zhengrui; Lu, Yongjun; He, Lei; Huang, Xishan; She, Zhigang

    2016-01-01

    Four new polyketides: nectriacids A-C (1-3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher's ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC50 values of 23.5 and 42.3 μM, respectively, which were more potent than positive control (acarbose, IC50, 815.3 μM). PMID:27136568

  3. Alpha-Glucosidase Inhibition and Hypoglycemic Activities of Sweitenia mahagoni Seed Extract

    Tutik Wresdiyat

    2015-04-01

    Full Text Available Inhibition of α-glucosidase and hypoglycemic activity are two effects commonly used to identify bioactive compounds with potential to treat diabetes. The objectives of this study were to analyse and compare the bioactive compounds and α-glucosidase inhibitory effect of four different types of Swietenia mahagoni seed extract, and to analyse the hypoglycemic activity of the greatest inhibition of α-glucosidase-extract in rats. The extracts were obtained using two different solvents (aqueous and ethanol and two different methods: maceration and reflux methods. This resulted in four types of extract varying by solvent and extraction method. Testing of these extracts for α-glucosidase inhibitory effect was carried out in vitro using spectrophotometer. Testing for hypoglycemic activity was carried out in vivo using rats. A total of 40 male Sprague-Dawley rats were divided into eight groups: (1 the negative control group, received an oral dose of aquadest only, (2 the positive control group, was given 90% sucrose orally without S. mahagoni seed extract, and five treated groups (3-7, were given 90% sucrose followed by the best extract-ethanolic S. mahagoni seed extract in doses of 100, 200, 300, 400, and 500 mg/kgBW, and (8 the acarbose group, was given 90% sucrose orally followed by acarbose. Glucose levels in each animal were measured at 0, 30, 60, 90, and 120 min after treatment. The results showed the greatest inhibition of α-glucosidase in ethanolic extract, using maceration methods. This ethanolic-maceration S. mahagoni seed extract also showed hypoglycemic effects in hyperglycemic rats at dose from 100 to 500 mg/kgBW. Ethanolic extract of S. mahagoni seed, using maceration method, can be proposed as potential antidiabetic agent.

  4. Comparison of Antioxidant Potential and Rat intestinal a-Glucosidases inhibitory Activities of Quercetin, Rutin, and Isoquercetin

    S-H Jo

    2009-12-01

    Full Text Available Summary: Inhibition of α-amylase and α-glucosidases involved in the digestion and absorption of carbohydrates can decrease the postprandial increase  of blood glucose level after a mixed carbohydrate diet. Therefore, the inhibitory activity of quercetin and its glycoside derivatives such as rutin and isoquercetin against rat intestinal α-glucosidases (sucrase, maltase, glucoamylase, and isomaltase and porcine pancreatic α-amylase were compared in vitro. Among the tested three flavonols, quercetin had the highest maltase, glucoamylase, and isomaltase inhibitory activities. The isomaltase and α-amylase inhibitory activities of the above three flavonols were also compared to a known type 2 diabetes drug (Acarbose, strong  α-amylase inhibitor. Compared  to acarbose, quercetin and its derivatives showed a significant inhibition of isomaltase but did not show high inhibitory activity against porcine pancreatic  α-amylase. Furthermore, the oxygen radical absorbance capacity (ORAC of these flavonols was evaluated. Quercetin had the highest peroxyl radical absorbing activity, followed by rutin and isoquercetin. These results suggest that the selected flavonols which have high ORAC value with α-glucosidase inhibitory activity and low α-amylase activity could be physiologically useful for treatment of diabetes, although in vivo experiments are needed. Industrial relevance: The α-glucosidase inhibitory activity and antioxidant activity in quercetin would be helpful to manage glucose uptake and the glucose-induced increased levels of mitochondrial reactive oxygen species (ROS linked to hyperglycemia. This in vitro study therefore provides the biochemical rationale for the benefit of quercetin-based dietary supplement and enzymatic conversion from rutin or isoquercetin to quercetin for enhancing bioactive food components using high rutin-contained grain such as buckwheat.  

  5. Effect of 'antidiabetis' herbal preparation on serum glucose and fructosamine in NOD mice.

    Petlevski, R; Hadzija, M; Slijepcevic, M; Juretic, D

    2001-05-01

    The antihyperglycemic effect of the Antidiabetis herbal preparation ((Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris), Millefollii herba (Achillea millefolium L.), Morii folium (Morus nigra L.), Valeriane radix (Valleriana officinalis L.), Urticae herba et radix (Urtica dioica L.)), patent No. P-9801091 Zagreb, Croatia was investigated. Two extracts were prepared: ethanol extract (extract 1), and ethanol extract from which ethanol was evaporated on a rotatory evaporator at a temperature of 45 degrees C (extract 2). Extract 1 and extract 2 were administered (in experiment 1) to alloxan-induced non-obese diabetic (NOD) mice in the same dose of 20 mg/kg. Blood glucose was determined before, and 10, 30, 60 and 120 min after the preparation administration. Extract 1 and extract 2 decreased the level of blood glucose by 10 and 20%, respectively, of the initial value (at 0 min, mean = 22.6 +/- 8.3 mmol/l). Serum levels of glucose and fructosamine were determined in NOD mice, NOD mice administered extract 2 in a dose of 20 mg/kg of extract 2, and NOD mice administered acarbose in a dose of 25 mg/100 g chow, in order to verify the hypoglycemic action of extract 2 (in experiment 2). Extract 2 and acarbose were admixed to the chow. The duration of treatment was 7 days. Significantly lower glucose (P < 0.05) and fructosamine (P < 0.001) levels were recorded in extract 2 treated NOD mice as compared with NOD mice. Study results showed extract 2 to significantly decrease the level of glucose and fructosamine in alloxan induced NOD mice. Our future studies will be focused on the search of active principles of the extracts. PMID:11297848

  6. In vitro evaluation of α-amylase inhibitory activity of some medicinal plants used in treatment of diabetes mellitus in Algeria and their effect on postprandial hyperglycemia in normal rats

    Asma BECHIRI

    2015-08-01

    Full Text Available Postprandial hyperglycemia is an early defect of type 2 diabetes, it is responsible of secondary complication which can affect many organs: heart, kidney, nervous system, and impaired their function. In this type of diabetes mellitus, the inhibition of digestive enzymes (α-amylase and α-glucosidases is a useful treatment to attenuate postprandial hyperglycemia. In this study we investigate in vitro, the α-amylase inhibitory potential of aqueous extract of leaves or roots of five selected plants recommended to treat diabetes in traditional Algerian medicine. They are also tested for their effect on reduction of postprandial hyperglycemia induced by starch loading in normal rats. The plant extracts showed a variable degree of inhibition of α-amylase. The most active sample is the aqueous extract of Phylleria angustofolia (PaE with an IC50=0.61mg/ml followed by extract of Olea europea (OeE, Juniperus oxydrus (JoE, Olea europea var. Sylvestris (OsE and Salvia officinalis (SoE. Acarbose (Acb, a standard inhibitor, exhibited an IC50 value of 0.07mg/ml. In an animal study, two plant extracts and acarbose exhibited an anti-hyperglycemic activity: SoE and PaE suppress significantly postprandial hyperglycemia response induced by starch loading in rats, as shown by the significant attenuation of the value of AUC0-180min by 60٪ (p<0.05 for PaE, 48٪ (p<0.05 for SoE and34٪ (p<0.05 for Ac, compared to control group. These findings suggest that among the five medicinal plants studied, Phylleria angustifolia and Salvia officinalis exert their antidiabetic effect by inhibition the digestion of complex carbohydrates, retarding glucose absorption and hence suppress postprandial hyperglycemia.

  7. Development of an antidiabetic formulation (ADJ6) and its inhibitory activity against α-amylase and α-glucosidase.

    Duraiswamy, Anand; Shanmugasundaram, Devanand; Sasikumar, Changam Sheela; Cherian, Sanjay M; Cherian, Kotturathu Mammen

    2016-07-01

    There has recently been much advancement in the diagnosis, treatment, and research of metabolic disorders, especially diabetes. Current research around the world is focused on finding an alternative source of treatment from natural resources for diabetic management, apart from the available synthetic medicines. The present study is a preliminary study of a polyherbal formulation using edible natural resources and an assessment of its antidiabetic activity. The formulation was screened for its phytochemical constituents, total phenols, flavonoids, and vitamin C content. It was also analyzed for its inhibitory effect against the digestive enzymes α-amylase and α-glucosidase, compared with the standard drug acarbose. The formulation showed the presence of major constituents such as steroids, cardiac glycosides, phenols, flavonoids, and saponins. It also had a high level of phenols (340 ± 2.5 mg/g), flavonoids (235.4 ± 8.3 mg/g), and vitamin C (470.8 ± 16.6 mg/g), and showed a half-maximal inhibitory concentration (IC50) value of 0.41 ± 0.03 mg/mL and 0.51 ± 0.01 mg/mL for amylase and glucosidase, respectively. The results showed that ADJ6 had a significant inhibitory activity on α-amylase and α-glucosidase; however, its inhibitory activity was less than that of acarbose. The plants that are formulated in ADJ6 possess potent antidiabetic activity. Thus, we found that ADJ6 is a potent lead for effective diabetic management; however, an evaluation of the formulation must be illustrated using an in vivo model. PMID:27419082

  8. Beneficial effect of dietary Ephedra sinica on obesity and glucose intolerance in high-fat diet-fed mice.

    Song, Moon-Koo; Um, Jae-Young; Jang, Hyeung-Jin; Lee, Byung-Cheol

    2012-04-01

    Obesity is a major contributor to both glucose intolerance and metabolic syndrome. In this study, we investigated the anti-obesity and anti-hyperglycemic effects of Ephedra sinica on high-fat diet-fed mice. Male ICR mice were divided into four groups; the normal group, the obese and diabetic control group treated with a high-fat diet, the positive control group treated with a high-fat diet containing acarbose, and the experimental group treated with a high-fat diet containing Ephedra sinica. The effects of Ephedra sinica on obesity and glucose intolerance were measured by an oral glucose tolerance test (OGTT), plasma biochemistry, body and epididymal fat weight; the expression of adiponectin, peroxisome-proliferator-activated receptor α (PPAR-α), tumor necrosis factor α (TNF-α) and leptin was also determined. Ephedra sinica reduced weight gain and epididymal fat accumulation, improved glucose intolerance on the OGTT, decreased triglycerides and increased high-density lipoprotein cholesterol compared to the controls. Moreover, it reduced weight gain and fasting glucose levels and improved HDL-cholesterol levels more than acarbose. Gene expression analysis revealed that Ephedra sinica upregulated the expression of adiponectin and PPAR-α, and downregulated the expression of TNF-α. From these results, we suggest that Ephedra sinica may reduce obesity and hyperglycemia by increasing PPAR-α and adiponectin and reducing TNF-α, and that it may have the potential to be used clinically as an ingredient in food or drugs effective in obesity-related glucose intolerance treatments. PMID:22969956

  9. Chemical Constituents of Malaysian U. cordata var. ferruginea and Their in Vitro α-Glucosidase Inhibitory Activities.

    Abdullah, Nur Hakimah; Salim, Fatimah; Ahmad, Rohaya

    2016-01-01

    Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1), 2,4-dihydroxybenzoic acid (2), 3,4-dihydroxybenzoic acid (3), scopoletin or 7-hydroxy-6-methoxy-coumarin (4), 3,4-dihydroxy-7-methoxycoumarin (5), quercetin (6), kaempferol (7), taxifolin (8), loganin (9) and β-sitosterol (10). Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR) spectral data and Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) spectroscopy and mass spectrometry (MS). In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3%) at a concentration of 1 mg/mL. The IC50 values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC50 values of 549 and 556 μg/mL compared to acarbose (IC50 580 μg/mL) while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus and

  10. Chemical Constituents of Malaysian U. cordata var. ferruginea and Their in Vitro α-Glucosidase Inhibitory Activities

    Nur Hakimah Abdullah

    2016-04-01

    Full Text Available Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1, 2,4-dihydroxybenzoic acid (2, 3,4-dihydroxybenzoic acid (3, scopoletin or 7-hydroxy-6-methoxy-coumarin (4, 3,4-dihydroxy-7-methoxycoumarin (5, quercetin (6, kaempferol (7, taxifolin (8, loganin (9 and β-sitosterol (10. Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR spectral data and Ultraviolet-Visible (UV-Vis, Fourier Transform Infrared (FTIR spectroscopy and mass spectrometry (MS. In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3% at a concentration of 1 mg/mL. The IC50 values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC50 values of 549 and 556 μg/mL compared to acarbose (IC50 580 μg/mL while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus

  11. 2007~2009年某院降糖药应用分析%Use of hypoglycemic drugs in a hospital: 2007-2009

    汪铁山; 陈莉婧; 张生潭; 林敬明

    2011-01-01

    Objective To investigate the characteristics and use of hypoglycemic drugs in a hospital of Guangzhou and to provide references for clinical rational use of drugs.Methods The use of hypoglycemic drugs from 2007 to 2009 was statistically analyzed, including the amount of drugs, consumption sum, DDDs, DDC and order ratio.Results The consumption sum of hypoglycemic drugs increased year by year with annual increase rates of 43.37% and 41.54 %, respectively.Of all the oral hypoglycemic drugs used, the consumption sum of acarbose tablets, metformin hydrochloride tablets and gliclazide modified release tablets remained top 3 over the 3 years, and acarbose tablets steadily ranked first in DDDs.Of all the insulin injections used, Humulin 70/30 took the lead in consumption quantity and consumption sum over the 3 years.Conclusion The use of hypoglycemic drugs is basically stable and reasonable in spite of their rapid increase in both consumption sum and quantity.%目的 了解广州市某医院降糖药应用特点和发展趋势,为临床合理用药提供参考.方法 对该院2007~2009年降糖药主要品种、销售金额、用药频度(DDDs)、日均费用(DDC)和排序比进行统计和分析.结果 3年来降糖药销售金额逐年增长,增长率分别为43.37%和41.54%.其中,口服降糖药销售金额排序中,阿卡波糖片、盐酸二甲双胍片和格列齐特缓释片连续3年均排在前3位,阿卡波糖片DDDs排序3年均为最大;注射用胰岛素类药物中,优泌灵70/30混合型使用数量及销售金额连续3年均位居榜首.结论 该院降糖药销售金额和使用数量增长较快,但其应用基本稳定、较为合理.

  12. Optimization of enzymatic production of anti-diabetic peptides from black bean (Phaseolus vulgaris L.) proteins, their characterization and biological potential.

    Mojica, Luis; de Mejía, Elvira González

    2016-02-01

    The aim was to optimize the production of bioactive peptides from black bean (Phaseolus vulgaris L.) protein isolate and to determine their biological potential using biochemical and in silico approaches. Protein fractions were generated using eight commercially available proteases after 2, 3 and 4 h and 1:20, 1:30 and 1:50 enzyme/substrate (E/S) ratios. The best combination of conditions to generate anti-diabetic peptides was with alcalase for 2 h and E/S of 1:20; with inhibition values for dipeptidyl peptidase IV (DPP-IV, 96.7%), α-amylase (53.4%) and α-glucosidase (66.1%). Generated peptides were characterized using LC-ESI-MS/MS. Molecular docking analysis was performed to predict individual peptide biological potential using DockingServer®. Peptides EGLELLLLLLAG, AKSPLF and FEELN inhibited DPP-IV more efficiently in silico through free energy interactions of -9.8, -9.6 and -9.5 kcal mol(-1), respectively, than the control sitagliptin (-8.67 kcal mol(-1)). The peptide TTGGKGGK (-8.97 kcal mol(-1)) had higher inhibitory potential on α-glucosidase compared to the control acarbose (-8.79 kcal mol(-1)). Peptides AKSPLF (-10.2 kcal mol(-1)) and WEVM (-10.1 kcal mol(-1)) generated a lower free energy interaction with the catalytic site of α-amylase in comparison with acarbose (-9.71 kcal mol(-1)). Bean peptides inhibited the tested enzymes through hydrogen bonds, polar and hydrophobic interactions. The main bindings on the catalytic site were with ASP192, GLU192 and ARG 253 on DPP-IV; TYR151, HIS201 and ILE235 on α-amylase; and ASP34, THR83 and ASN32 on α-glucosidase. For the first time, a systematic evaluation and characterization of the anti-diabetic peptides from black bean protein isolate is presented with the potential for inhibiting important molecular markers related to diabetes. PMID:26824775

  13. Rapid identification of α-glucosidase inhibitors from Phlomis tuberosa by Sepbox chromatography and thin-layer chromatography bioautography.

    Yingbo Yang

    Full Text Available Alpha-glucosidase inhibitors currently form an important basis for developing novel drugs for diabetes treatment. In our preliminary tests, the ethyl acetate fraction of Phlomis tuberosa extracts showed significant α-glucosidase inhibitory activity (IC₅₀ = 100 μg/mL. In the present study, a combined method using Sepbox chromatography and thin-layer chromatography (TLC bioautography was developed to probe α-glucosidase inhibitors further. The ethyl acetate fraction of P. tuberosa extracts was separated into 150 individual subfractions within 20 h using Sepbox chromatography. Then, under the guidance of TLC bioautography, 20 compounds were successfully isolated from these fractions, including four new diterpenoids [14-hydroxyabieta-8,11,13-triene-11-carbaldehyde-18-oic-12-carboxy-13-(1-hydroxy-1-methylethyl-lactone (1, 14-hydroxyabieta-8,11,13-triene-17-oic-12-carboxy-13-(1-hydroxy-1-methylethyl-lactone (2, 14,16-dihydroxyabieta-8,11,13-triene-15,17-dioic acid (3, and phlomisol (15,16-eposy-8,13(16,14-labdatrien-19-ol (4], and 16 known compounds. Activity estimation indicated that 15 compounds showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 0.067-1.203 mM than the positive control, acarbose (IC50 = 3.72 ± 0.113 mM. This is the first report of separation of α-glucosidase inhibitors from P. tuberosa.

  14. An in vivo invertebrate evaluation system for identifying substances that suppress sucrose-induced postprandial hyperglycemia

    Matsumoto, Yasuhiko; Ishii, Masaki; Sekimizu, Kazuhisa

    2016-01-01

    Sucrose is a major sweetener added to various foods and beverages. Excessive intake of sucrose leads to increases in blood glucose levels, which can result in the development and exacerbation of lifestyle-related diseases such as obesity and diabetes. In this study, we established an in vivo evaluation system using silkworms to explore substances that suppress the increase in blood glucose levels caused by dietary intake of sucrose. Silkworm hemolymph glucose levels rapidly increased after intake of a sucrose-containing diet. Addition of acarbose or voglibose, α-glycosidase inhibitors clinically used for diabetic patients, suppressed the dietary sucrose-induced increase in the silkworm hemolymph glucose levels. Screening performed using the sucrose-induced postprandial hyperglycemic silkworm model allowed us to identify some lactic acid bacteria that inhibit the increase in silkworm hemolymph glucose levels caused by dietary intake of sucrose. The inhibitory effects of the Lactococcus lactis #Ll-1 bacterial strain were significantly greater than those of different strains of lactic acid bacteria. No effect of the Lactococcus lactis #Ll-1 strain was observed in silkworms fed a glucose diet. These results suggest that the sucrose diet-induced postprandial hyperglycemic silkworm is a useful model for evaluating chemicals and lactic acid bacteria that suppress increases in blood glucose levels. PMID:27194587

  15. Evaluation of α-amylase inhibitory potential of three medicinally important traditional wild food plants of India

    K.S.N Jyothi

    2011-01-01

    Full Text Available Naturally available α-amylase inhibitors from medicinally important plants are shown to be effective in managing postprandial hyperglycemia (PPHG which is of major concern in Type -2 diabetes. Three wild food plants namely Oxalis corniculata, Basella rubra , and Cocculus hirsutus with known traditional medicinal values were tested for α-amylase inhibition in order to evaluate their inhibitory potential on porcine pancreatic α-amylase. A total of 15 extracts obtained from three plants by aqueous and solvent extraction have been tested for their inhibitory potential against porcine pancreatic α-amylase. Of the fifteen extracts, five extracts showed concentration-dependent potent inhibition of >75% with IC50 (half maximal inhibitory concentration values much less than that of standard anti-diabetic drug acarbose namely aqueous extract of Oxalis corniculata 89.87% (100 μg/ml, IC 50 -68.08 0.06, chloroform, acetone and methanol extracts of Cocculus hirsutus exhibited 83.33% (60 μg/ml, IC 50 -70.48 18.39, 79.10% (100 μg/ml, IC 50 -80.77 0.63, 77.2% (100 μg/ml, IC 50 -80.11 2.23 respectively. The other extracts of the plants showed inhibition, but not statistically significant. Thus, these extracts showing potent inhibition might prove to be efficient sources for the extraction of natural α-amylase inhibitors.

  16. Pharmacotherapy of polycystic ovary syndrome--an update.

    Saha, Lekha; Kaur, Sharonjeet; Saha, Pradip Kumar

    2012-02-01

    Polycystic ovary syndrome (PCOS) is a persisting challenge to clinical and basic research scientists as none of the presently available medications have been fully able to combat these consequences. The aim of the present review is to summarize the different lines of treatment available for the different symptomologies that women with PCOS presents. In this comprehensive review, search was made for various treatment options available for PCOS by using Cochrane library, Pubmed, Medline, in addition to the relevant printed medical journals and periodicals. The search results revealed that oral contraceptives containing oestrogen and progesterone regularize the menstruation, antiandrogens like spironolactone and drosperinone have proven to be effective in hirsutism and acne, clomiphene is the gold standard for ovulation induction, but multiple pregnancies and clomiphene failure add to its limitation. Hence, aromatase inhibitors like letrozole, low-dose gondotropins, and ovarian drilling procedure have shown to be beneficial effect in clomiphene-resistant cases. Insulin sensitizers such as metformin, thiazolidinediones, and d-chiro-inositol increase insulin sensitivity and improve ovulation rate. Recently, melatonin, N-acetyl cysteine, acarbose, and statins have shown positive results in different symptomologies of PCOS. The results show that PCOS treatment constitutes varied line of treatment depending upon the clinical features with which a woman is presenting. Still, unfortunately, none of the treatments are fully able to combat the PCOS. PMID:21210850

  17. Antidiabetic Indian Plants: A Good Source of Potent Amylase Inhibitors

    Menakshi Bhat

    2011-01-01

    Full Text Available Diabetes is known as a multifactorial disease. The treatment of diabetes (Type II is complicated due to the inherent patho-physiological factors related to this disease. One of the complications of diabetes is post-prandial hyperglycemia (PPHG. Glucosidase inhibitors, particularly α-amylase inhibitors are a class of compounds that helps in managing PPHG. Six ethno-botanically known plants having antidiabetic property namely, Azadirachta indica Adr. Juss.; Murraya koenigii (L. Sprengel; Ocimum tenuflorum (L. (syn: Sanctum; Syzygium cumini (L. Skeels (syn: Eugenia jambolana; Linum usitatissimum (L. and Bougainvillea spectabilis were tested for their ability to inhibit glucosidase activity. The chloroform, methanol and aqueous extracts were prepared sequentially from either leaves or seeds of these plants. It was observed that the chloroform extract of O. tenuflorum; B. spectabilis; M. koenigii and S. cumini have significant α-amylase inhibitory property. Plants extracts were further tested against murine pancreatic, liver and small intestinal crude enzyme preparations for glucosidase inhibitory activity. The three extracts of O. tenuflorum and chloroform extract of M. koenigi showed good inhibition of murine pancreatic and intestinal glucosidases as compared with acarbose, a known glucosidase inhibitor.

  18. In vitro α-amylase inhibitory activity and in vivo hypoglycemic effect of ethyl acetate extract of Mallotus repandus (Willd.) Muell. stem in rat model

    Md. Rakib Hasan; Nizam Uddin; Md. Monir Hossain; Md. Mahadi Hasan; Md. Emtiaz Yousuf; Swagata Sarker Lopa; Tasmina Rahman

    2014-01-01

    Objective: To investigate the therapeutic effects of ethyl acetate extract of Mallotus repandus stem in α-amylase inhibitory activity (in vitro) and hypoglycemic activity in normal and glucose induced hyperglycemic rats (in vivo). Methods: Ethyl acetate extract of Mallotus repandus stem was tested for the presence of phytochemical constituents, α-amylase inhibitory activity and hypoglycemic effect in normal rats and glucose induced hyperglycemic rats.Results:Presence of different types of phytochemicals was identified in the extract. The extract has moderate α-amylase inhibitory activity [IC50=(2.038±0.033) mg/mL] as compared to acarbose. The does 1000 mg/kg significantly reduced (P<0.0100) fasting blood glucose level in normal rats. In oral glucose tolerance test, both 1000 and 2000 mg/kg doses showed good hypoglycemic activity (P<0.0001) like glibenclamide in each specific hour after administration. Overall time effect in oral glucose tolerance test was found extremely significant (P<0.0001) with F (3, 48) value=202.4.Conclusions:These findings suggest that this plant may be a potential source for the development of new oral hypoglycemic agent.

  19. Antioxidant and antidiabetic activities of 11 herbal plants from Hyrcania region, Iran

    Hossein Dehghan

    2016-01-01

    Full Text Available In the present study, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, α-amylase and α-glucosidase inhibition activities, and total phenolic contents of n-hexane, ethyl acetate, and methanol extracts of various parts of Allium paradoxum, Buxus hyrcana, Convolvulus persicus, Eryngium caucasicum, Heracleum persicum, Pimpinella affinis, Parrotia persica, Primula heterochroma, Pyrus boissieriana, Ruscus hyrcanus, and Smilax excelsa were investigated. These plants, which mostly serve as food flavoring, were collected from Hyrcania region, Sari, Iran. Some extracts of H. persicum, S. excels, P. boissieriana, P. persica, and P. heterochroma exhibited significant antidiabetic activities in α-amylase and α-glucosidase assays, more effective than acarbose (concentrations that cause 50% inhibition = 75.7 μg/mL and 6.1 μg/mL against α-amylase and α-glucosidase, respectively. Also, C. persicus, P. boissieriana, and P. heterochroma showed strong antioxidant activities, compared with butylated hydroxytoluene (concentration that causes 50% inhibition = 16.7 μg/mL. In conclusion, this study can recommend these plants as good candidates for further investigations to find potent antidiabetic natural products or probable lead compounds. Statistical analysis showed significant correlation between the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and total phenolic contents (r = 0.711, p < 0.001.

  20. Comparative evaluation of polysaccharides isolated from Astragalus, oyster mushroom, and yacon as inhibitors of α-glucosidase.

    Zhu, Zhen-Yuan; Zhang, Jing-Yi; Chen, Li-Jing; Liu, Xiao-Cui; Liu, Yang; Wang, Wan-Xiao; Zhang, Yong-Min

    2014-04-01

    The incidence of diabetes has increased considerably, and become the third serious chronic disease following cancer and cardiovascular diseases. Though acarbose, metformin, and 1-deoxynojirimycin have good efficacy for clinical application as hypoglycemic drugs, their expensive costs and some degree of side effects have limited their clinical application. Recently, increasing attention has concentrated on the polysaccharides from natural plant and animal sources for diabetes. In order to illustrate the pharmaceutical activity of polysaccharides as natural hypoglycemic agents, polysaccharides isolated from Astragalus, oyster mushroom, and Yacon were evaluated for their inhibitory effects on α-glucosidase. Polysaccharides were extracted and purified from Astragalus, Oyster mushroom, and Yacon with hot water at 90 °C for 3 h, respectively. The total sugar content of the polysaccharide was determined by the phenol-sulfuric acid method. The α-glucosidase inhibitory activity was measured by the glucose oxidase method. The results exhibited that the inhibitory effects on α-glucosidase were in decreasing order, Astragalus > oyster mushroom > Yacon. The α-glucosidase inhibition percentage of Astragalus polysaccharide and oyster mushroom polysaccharide were over 40% at the polysaccharide concentration of 0.4 mg·mL(-1). The IC50 of Astragalus polysaccharide and oyster mushroom polysaccharide were 0.28 and 0.424 mg·mL(-1), respectively. The information obtained from this work is beneficial for the use polysaccharides as a dietary supplement for health foods and therapeutics for diabetes. PMID:24863354

  1. Isolation of a new phlorotannin, a potent inhibitor of carbohydrate-hydrolyzing enzymes, from the brown alga Sargassum patens.

    Kawamura-Konishi, Yasuko; Watanabe, Natsuko; Saito, Miki; Nakajima, Noriyuki; Sakaki, Toshiyuki; Katayama, Takane; Enomoto, Toshiki

    2012-06-01

    Ethanol extracts from 15 kinds of marine algae collected from the coast of the Noto Peninsula in Japan were examined for their inhibitory effects on human salivary α-amylase. Four extracts significantly suppressed the enzyme activity. An inhibitor was purified from the extract of Sargassum patens . The compound was a new phloroglucinol derivative, 2-(4-(3,5-dihydroxyphenoxy)-3,5-dihydroxyphenoxy) benzene-1,3,5-triol (DDBT), which strongly suppressed the hydrolysis of amylopectin by human salivary and pancreatic α-amylases. The 50% inhibitory activity (IC(50)) for α-amylase inhibition of DDBT (3.2 μg/mL) was much lower than that of commercially available α-amylase inhibitors, acarbose (26.3 μg/mL), quercetagetin (764 μg/mL), and α-amylase inhibitor from Triticum aestivum (88.3 μg/mL). A kinetic study indicated that DDBT was a competitive α-amylase inhibitor with a K(i) of 1.8 μg/mL. DDBT also inhibited rat intestinal α-glucosidase with an IC(50) value of 25.4 μg/mL for sucrase activity and 114 μg/mL for maltase activity. These results suggest that DDBT, a potent inhibitor of carbohydrate-hydrolyzing enzymes, may be useful as a natural nutraceutical to prevent diabetes. PMID:22594840

  2. Grape skin phenolics as inhibitors of mammalian α-glucosidase and α-amylase--effect of food matrix and processing on efficacy.

    Lavelli, V; Sri Harsha, P S C; Ferranti, P; Scarafoni, A; Iametti, S

    2016-03-01

    Type-2 diabetes is continuously increasing worldwide. Hence, there is a need to develop functional foods that efficiently alleviate damage due to hyperglycaemia complications while meeting the criteria for a sustainable food processing technology. Inhibition of mammalian α-amylase and α-glucosidase was studied for white grape skin samples recovered from wineries and found to be higher than that of the drug acarbose. In white grape skins, quercetin and kaempferol derivatives, analysed by UPLC-DAD-MS, and the oligomeric series of catechin/epicatechin units and their gallic acid ester derivatives up to nonamers, analysed by MALDI-TOF-MS were identified. White grape skin was then used for enrichment of a tomato puree (3%) and a flat bread (10%). White grape skin phenolics were found in the extract obtained from the enriched foods, except for the higher mass proanthocyanidin oligomers, mainly due to their binding to the matrix and to a lesser extent to heat degradation. Proanthocyanidin solubility was lower in bread, most probably due to formation of binary proanthocyanin/protein complexes, than in tomato puree where possible formation of ternary proanthocyanidin/protein/pectin complexes can enhance solubility. Enzyme inhibition by the enriched foods was significantly higher than for unfortified foods. Hence, this in vitro approach provided a platform to study potential dietary agents to alleviate hyperglycaemia damage and suggested that grape skin phenolics could be effective even if the higher mass proanthocyanidins are bound to the food matrix. PMID:26943361

  3. In vitro screening of medicinal plants used in Mexico as antidiabetics with glucosidase and lipase inhibitory activities.

    Ramírez, Guillermo; Zavala, Miguel; Pérez, Julia; Zamilpa, Alejandro

    2012-01-01

    This work shows the inhibitory effect on glucosidase and lipase enzymes of 23 medicinal plants described as traditional treatments for diabetes in several Mexican sources. Hydroalcoholic extracts of selected plants were evaluated at 1 mg/mL for glucosidase and 0.25 mg/mL for lipase inhibitory activities, respectively. Camellia sinensis, acarbose, and orlistat were used as positive controls. Dose-response curves were done with the most active species. Sixty percent of all tested extracts inhibited more than 25% of α-glucosidase activity. C. sinensis displayed an inhibition of 85% (IC(50) = 299 μg/mL), while Ludwigia octovalvis and Iostephane heterophylla showed the highest inhibition (82.7 %, IC(50) = 202 μg/mL and 60.6%, CI(50) = 509 μg/mL, resp.). With respect to lipase activity, L. octovalvis and Tecoma stans were the most inhibiting treatments (31.4%, IC(50) = 288 μg/mL; 27.2%, IC(50) = 320 μg/mL), while C. sinensis displayed 45% inhibition (IC(50) = 310 μg/mL). These results indicate that a high proportion of plants used in Mexico as treatment for diabetes displays significant inhibition of these digestive enzymes. PMID:23082084

  4. In Vitro Screening of Medicinal Plants Used in Mexico as Antidiabetics with Glucosidase and Lipase Inhibitory Activities

    Guillermo Ramírez

    2012-01-01

    Full Text Available This work shows the inhibitory effect on glucosidase and lipase enzymes of 23 medicinal plants described as traditional treatments for diabetes in several Mexican sources. Hydroalcoholic extracts of selected plants were evaluated at 1 mg/mL for glucosidase and 0.25 mg/mL for lipase inhibitory activities, respectively. Camellia sinensis, acarbose, and orlistat were used as positive controls. Dose-response curves were done with the most active species. Sixty percent of all tested extracts inhibited more than 25% of α-glucosidase activity. C. sinensis displayed an inhibition of 85% (IC50 = 299 μg/mL, while Ludwigia octovalvis and Iostephane heterophylla showed the highest inhibition (82.7 %, IC50 = 202 μg/mL and 60.6%, CI50 = 509 μg/mL, resp.. With respect to lipase activity, L. octovalvis and Tecoma stans were the most inhibiting treatments (31.4%, IC50 = 288 μg/mL; 27.2%, IC50 = 320 μg/mL, while C. sinensis displayed 45% inhibition (IC50 = 310 μg/mL. These results indicate that a high proportion of plants used in Mexico as treatment for diabetes displays significant inhibition of these digestive enzymes.

  5. Phlorotannins from Alaskan Seaweed Inhibit Carbolytic Enzyme Activity

    Kellogg, Joshua; Grace, Mary H.; Lila, Mary Ann

    2014-01-01

    Global incidence of type 2 diabetes has escalated over the past few decades, necessitating a continued search for natural sources of enzyme inhibitors to offset postprandial hyperglycemia. The objective of this study was to evaluate coastal Alaskan seaweed inhibition of α-glucosidase and α-amylase, two carbolytic enzymes involved in serum glucose regulation. Of the six species initially screened, the brown seaweeds Fucus distichus and Alaria marginata possessed the strongest inhibitory effects. F. distichus fractions were potent mixed-mode inhibitors of α-glucosidase and α-amylase, with IC50 values of 0.89 and 13.9 μg/mL, respectively; significantly more efficacious than the pharmaceutical acarbose (IC50 of 112.0 and 137.8 μg/mL, respectively). The activity of F. distichus fractions was associated with phlorotannin oligomers. Normal-phase liquid chromatography-mass spectrometry (NPLC-MS) was employed to characterize individual oligomers. Accurate masses and fragmentation patterns confirmed the presence of fucophloroethol structures with degrees of polymerization from 3 to 18 monomer units. These findings suggest that coastal Alaskan seaweeds are sources of α-glucosidase and α-amylase inhibitory phlorotannins, and thus have potential to limit the release of sugar from carbohydrates and thus alleviate postprandial hyperglycemia. PMID:25341030

  6. Triterpene saponins with α-glucosidase inhibition and cytotoxic activity from the leaves of Schefflera sessiliflora.

    Nguyen, Tan Phat; Le, Tien Dung; Phan, Nhat Minh; Bui, Trong Dat; Mai, Dinh Tri

    2016-06-01

    From the leaves of Schefflera sessiliflora De P. V., two new triterpene saponins including one oleanane-type saponin, named scheffleraside C (1) and one lupane-type saponin scheffleraside D (2), together with six known triterpene saponins (3-8), were isolated by various chromatography methods. Among them, 3 was found for the first time from natural sources, while 6-8 were isolated for the first time from the genus Schefflera. Their structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments, and comparison of their NMR data with previously reported data. Their α-glucosidase inhibition and cytotoxic activity against MCF-7 human breast cancer cell lines were evaluated. The isolates (1, 3-5, 8) showed stronger α-glucosidase inhibitory activity (IC50 = 5.99-76.58 μM) than the standard drug acarbose (IC50 = 214.50 μM). At the concentration of 100 μg/ml, the isolates (1, 2) showed appreciable cytotoxic activity (67.92, 63.83%, respectively). PMID:26690849

  7. Phenylethanoid glycosides and phenolic glycosides from stem bark of Magnolia officinalis.

    Xue, Zhenzhen; Yan, Renyi; Yang, Bin

    2016-07-01

    An investigation of the hydrophilic constituents of the stem bark of Magnolia officinalis was performed and which led to isolation and identification of twenty-one previously unreported glycosides. These included eleven phenylethanoid glycosides, magnolosides F-P, and ten phenolic glycosides, magnolosides Q-Z, along with eight known compounds. Their structures were elucidated on the basis of extensive spectroscopic analyses and chemical hydrolysis methods, as well as by comparison with literature data. Most of the phenylethanoid glycosides contained an allopyranose moiety, which is rare in the plant kingdom. Magnolosides I and K as well as 2-(3,4-dihydroxyphenyl) ethanol 1-O-[4-O-caffeoyl-2-O-α-l-rhamnopyranosyl-3-O-α-l-rhamnopyranosyl-6-O-β-d-glucopyranosyl]-β-d-glucopyranoside showed more potent α-glucosidase inhibitory effects (IC50 values of 0.13, 0.27, and 0.29mM, respectively) than the positive control, acarbose (IC50 value of 1.09mM) in vitro. Magnolosides H, E and D also showed moderate cytotoxicity against MGC-803 and HepG2 cells with IC50 values of 13.59-17.16μM and 29.53-32.46μM, respectively. PMID:27086163

  8. Synthesis, In vitro and Docking Studies of New Flavone Ethers as α-Glucosidase Inhibitors.

    Imran, Syahrul; Taha, Muhammad; Ismail, Nor Hadiani; Kashif, Syed Muhammad; Rahim, Fazal; Jamil, Waqas; Wahab, Habibah; Khan, Khalid Mohammed

    2016-03-01

    We report herein the synthesis, α-glucosidase inhibition and docking studies for a series of 3-15 new flavones. A simple nucleophilic substitution reaction takes place between 3'hydroxyflavone (2) with halides to afford the new flavones. Chalcone (1), 3'hydroxyflavone (2) and the newly synthesized flavones (3-15) were being evaluated for their ability to inhibit activity of α-glucosidase. Compounds 2, 3, 5, 7-10 and 13 showed good inhibitory activity with IC50 values ranging between 1.26 and 36.44 μM as compared to acarbose (IC50 = 38.25 ± 0.12 μM). Compounds 5 (5.45 ± 0.08 μM), 7 (1.26 ± 0.01 μM) and 8 (8.66 ± 0.08 μM) showed excellent inhibitory activity, and this may be due to trifluoromethyl substitution that is common for these compounds. Compound 7, a 2,5-trifluoromethyl-substituted compound, recorded the highest inhibition activity, and it is thirty times better than the standard drug. Docking studies for compound 7 suggest that both trifluoromethyl substituents are well positioned in a binding pocket surrounded by Phe300, Phe177, Phe157, Ala278, Asp68, Tyr71 and Asp214. The ability of compound 7 to interact with Tyr71 and Phe177 is extremely significant as they are found to be important for substrates recognition by α-glucosidase. PMID:26362113

  9. Inhibition of α-Glucosidase by Thiosulfinate as a Target for Glucose Modulation in Diabetic Rats

    Abdulrahman L. Al-Malki

    2016-01-01

    Full Text Available Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and organ damage. α-glucosidase is a hydrolytic enzyme that increases the glucose absorption rate and subsequently elevates blood glucose levels. Garlic (Allium sativum L. is a rich source of several phytonutrients, including thiosulfinate (THIO. The aim of this study was to evaluate the ability of THIO, a potent inhibitor of intestinal α-glucosidase, to reduce postprandial blood glucose. Male albino rats were randomly assigned to five different groups (n=10/group. Group 1 served as the control group. Groups 2–5 were injected intraperitoneally with a single dose of streptozotocin (STZ to induce diabetes. Group 2 comprised untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.. Group 5 was the positive control having diabetic rats treated orally with acarbose (10 mg/kg body weight/day; positive control. Diabetic rats treated with THIO displayed a significant blood glucose reduction (p<0.001 and < 0.01 by analysis of variance, resp. and a significant elevation in insulin compared with that of untreated rats. THIO is an effective noncompetitive intestinal α-glucosidase inhibitor that promotes hypoglycemic action (p<0.001 in STZ-injected rats. THIO is a promising agent for the management of postprandial hyperglycemia.

  10. Inhibition of α-Glucosidase by Thiosulfinate as a Target for Glucose Modulation in Diabetic Rats.

    Al-Malki, Abdulrahman L

    2016-01-01

    Postprandial hyperglycemia is a predisposing factor for vascular dysfunction and organ damage. α-glucosidase is a hydrolytic enzyme that increases the glucose absorption rate and subsequently elevates blood glucose levels. Garlic (Allium sativum L.) is a rich source of several phytonutrients, including thiosulfinate (THIO). The aim of this study was to evaluate the ability of THIO, a potent inhibitor of intestinal α-glucosidase, to reduce postprandial blood glucose. Male albino rats were randomly assigned to five different groups (n = 10/group). Group 1 served as the control group. Groups 2-5 were injected intraperitoneally with a single dose of streptozotocin (STZ) to induce diabetes. Group 2 comprised untreated diabetic rats. Groups 3 and 4 contained diabetic rats that were given THIO orally (20 mg/kg body weight/day and 40 mg/kg body weight/day, resp.). Group 5 was the positive control having diabetic rats treated orally with acarbose (10 mg/kg body weight/day; positive control). Diabetic rats treated with THIO displayed a significant blood glucose reduction (p < 0.001 and < 0.01 by analysis of variance, resp.) and a significant elevation in insulin compared with that of untreated rats. THIO is an effective noncompetitive intestinal α-glucosidase inhibitor that promotes hypoglycemic action (p < 0.001) in STZ-injected rats. THIO is a promising agent for the management of postprandial hyperglycemia. PMID:27051452

  11. Effect of Long-Term Dietary Arginyl-Fructose (AF on Hyperglycemia and HbA1c in Diabetic db/db Mice

    Kwang-Hyoung Lee

    2014-05-01

    Full Text Available We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch with and without AF (4% in the diet for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001 and body weight (p < 0.001. The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001. Dietary treatment of acarbose® (0.04% in diet, a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.

  12. Synthesis of water soluble glycosides of pentacyclic dihydroxytriterpene carboxylic acids as inhibitors of α-glucosidase.

    Xu, Jiancong; Nie, Xuliang; Hong, Yanping; Jiang, Yan; Wu, Guoqiang; Yin, Xiaoli; Wang, Chunrong; Wang, Xiaoqiang

    2016-04-01

    A series of compounds were synthesized by glycosylation of maslinic acid (MA) and corosolic acid (CA) with monosaccharides and disaccharides, and the structures of the derivatives were elucidated by standard spectroscopic methods including (1)H NMR, (13)C NMR and HRMS. The α-glucosidase inhibitory activities of all the novel compounds were evaluated in vitro. The solubility and inhibitory activity of α-glucosidase assays showed that the bis-disaccharide glycosides of triterpene acids possessed higher water solubility and α-glucosidase inhibitory activities than the bis-monosaccharide glycosides. Among these compounds, maslinic acid bis-lactoside (8e, IC50 = 684 µM) and corosolic acid bis-lactoside (9e, IC50 = 428 µM) had the best water solubility, and 9e exhibited a better inhibitory activity than acarbose (IC50 = 478 µM). However, most of glycosylated derivatives possessed lower inhibitory activities than the parent compounds, although their water solubility was enhanced obviously. Moreover, the kinetic inhibition studies indicated that 9e was a non-competitive inhibitor, and structure-activity relationships of the derivatives are also discussed. PMID:26974355

  13. Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts and α-Glucosidase Inhibitory Activities of Different Fractionations.

    Yan, Shuxia; Zhang, Xianan; Wen, Xin; Lv, Qiang; Xu, Changjie; Sun, Chongde; Li, Xian

    2016-01-01

    Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak(®) cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC50 = 15.4-69.5 μg/mL), which were higher than that of positive control acarbose (IC50 = 383.2 μg/mL). Four purified compounds 1-4 exerted α-glucosidase inhibitory activities, with IC50 values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved. PMID:27589714

  14. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase - enzymes related to hyperglycemia.

    Su, Chun-Han; Lai, Min-Nan; Ng, Lean-Teik

    2013-04-25

    In Asia, medicinal mushrooms have been popularly used as folk medicine and functional foods. In this study, our aim was to examine the inhibitory effects of six medicinal mushrooms on key enzymes (α-amylase and α-glucosidase) related to hyperglycemia; chemical profiles of bioactive extracts were also examined. The results showed that the n-hexane extract of Coriolus versicolor had the strongest anti-α-amylase activity, while the n-hexane extract of Grifola frondosa showed the most potent anti-α-glucosidase activity. Compared with acarbose, the anti-α-amylase activity of all mushroom extracts was weaker, however a stronger anti-α-glucosidase activity was noted. GC-MS analysis showed that the magnitude of potency of inhibiting α-glucosidase activity varied with the levels of oleic acid and linoleic acid present in the extracts. These findings were consistent with the IC50 values of these free fatty acids on inhibiting α-glucosidase activity. Taken together, this study suggests that oleic acid and linoleic acid could have contributed to the potent anti-α-glucosidase activity of selected medicinal mushrooms. PMID:23396484

  15. Structural characterization and inhibition on α-d-glucosidase activity of non-starch polysaccharides from Fagopyrum tartaricum.

    Wang, Xiao-Ting; Zhu, Zhen-Yuan; Zhao, Liang; Sun, Hui-Qing; Meng, Meng; Zhang, Jin-Yu; Zhang, Yong-Min

    2016-11-20

    In the present study, the crude polysaccharide was extracted from Fagopyrum tartaricum and purified by Sephadex G-25 and G-75 column to produce a polysaccharide fraction termed TBP-II. Its average molecular weight was 26kDa. The structural characterization of TBP-II was investigated by gas chromatography, periodate oxidation-Smith degradation, Methylation and NMR. Congo red was applied to explore its advanced structures. The results revealed that chemical composition and structural characteristic of TBP-II was mainly consisted of galactose, arabinose, xylose and glucose with a molar ratio of 0.7:1:6.3:74.2. The backbone of TBP-II was composed of (1→4)-linked α-d-glucopyranosyl (Glcp), while the branches comprised of (1→3)-linked α-d-glucopyranosyl (Glcp), (1→6)-linked α-d-galactopyranosyl (Galp) and (1→2,4)-linked α-d-rhamnopyranosyl (Rhap). The structure of TBP-II was 1,3 and 1,6-branched-galactorhamnoglucan that had a linear backbone of (1→4)-linked α-d-glucopyranose (Glcp). Using Congo red assay showed that it was absent of triple helix structure. The α-d-glucosidase inhibitory activity of TBP-II was determined using acarbose as positive control. The result showed that the inhibition rate depended on the concentration of polysaccharides. PMID:27561539

  16. Determination of a-glucosidase inhibitory activity from selected Fabaceae plants.

    Dej-Adisai, Sukanya; Pitakbut, Thanet

    2015-09-01

    Nineteen plants from Fabaceae family, which were used in Thai traditional medicine for treatment of diabetes, were determined of α-glucosidase inhibitory activity via enzymatic reaction. In this reaction, α-glucosidase was used as enzyme, which, reacted with the substrate, p-nitrophenol-D-glucopyranoside (pNPG). After that the product, p-nitro phenol (pNP) will be occurred and observed the yellow colour at 405 nm. In this study, acarbose was used as positive standard which, inhibited this enzyme with IC₅₀ as 331 ± 4.73 μg/ml. Caesalpinia pulcherrima leaves showed the highest activity with IC₅₀ as 436.97 ± 9.44 μg/ml. Furthermore, Bauhinia malabarica leaves presented moderately activity with IC₅₀ as 745.08 ± 11.15 μg/ml. However, the other plants showed mild to none activity of α-glucosidase inhibition. Accordingly, this study can support anti-diabetes of these plants in traditional medicine and it will be the database of the biological activity of Fabaceae plant. PMID:26408887

  17. Zinc oxide nanoparticles as novel alpha-amylase inhibitors

    Dhobale, Sandip; Thite, Trupti; Laware, S. L.; Rode, C. V.; Koppikar, Soumya J.; Ghanekar, Ruchika-Kaul; Kale, S. N.

    2008-11-01

    Amylase inhibitors, also known as starch blockers, contain substances that prevent dietary starches from being absorbed by the body via inhibiting breakdown of complex sugars to simpler ones. In this sense, these materials are projected as having potential applications in diabetes control. In this context, we report on zinc oxide nanoparticles as possible alpha-amylase inhibitors. Zinc oxide nanoparticles have been synthesized using soft-chemistry approach and 1-thioglycerol was used as a surfactant to yield polycrystalline nanoparticles of size ˜18 nm, stabilized in wurtzite structure. Conjugation study and structural characterization have been done using x-ray diffraction technique, Fourier transform infrared spectroscopy, UV-visible spectroscopy, and transmission electron microscopy. Cytotoxicity studies on human fibrosarcoma (HT-1080) and skin carcinoma (A-431) cell lines as well as mouse primary fibroblast cells demonstrate that up to a dose of 20 μg/ml, ZnO nanoparticles are nontoxic to the cells. We report for the first time the alpha-amylase inhibitory activity of ZnO nanoparticles wherein an optimum dose of 20 μg/ml was sufficient to exhibit 49% glucose inhibition at neutral pH and 35 °C temperature. This inhibitory activity was similar to that obtained with acarbose (a standard alpha-amylase inhibitor), thereby projecting ZnO nanoparticles as novel alpha-amylase inhibitors.

  18. Purification, enzymatic characterization, and nucleotide sequence of a high-isoelectric-point alpha-glucosidase from barley malt

    Frandsen, T P; Lok, F; Mirgorodskaya, E;

    2000-01-01

    .5, and catalyzed the hydrolysis by a retaining mechanism, as shown by nuclear magnetic resonance. Acarbose was a strong inhibitor (K(i) = 1.5 microM). Molecular recognition revealed that all OH-groups in the non-reducing ring and OH-3 in the reducing ring of maltose formed important hydrogen bonds to the...... enzyme in the transition state complex. Mass spectrometry of tryptic fragments assigned the 92-kD protein to a barley cDNA (GenBank accession no. U22450) that appears to encode an alpha-glucosidase. A corresponding sequence (HvAgl97; GenBank accession no. AF118226) was isolated from a genomic phage...... library using a cDNA fragment from a barley cDNA library. HvAgl97 encodes a putative 96.6-kD protein of 879 amino acids with 93.8% identity to the protein deduced from U22450. The sequence contains two active site motifs of glycoside hydrolase family 31. Three introns of 86 to 4,286 bp interrupt the...

  19. Synthesis and biological evaluation of novel 1,2,4-triazine derivatives bearing carbazole moiety as potent α-glucosidase inhibitors.

    Wang, Guangcheng; Wang, Jing; He, Dianxiong; Li, Xin; Li, Juan; Peng, Zhiyun

    2016-06-15

    A new series of 1,2,4-triazine derivatives bearing carbazole moiety 7a-7p were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent α-glucosidase inhibitory activity, with IC50 values in the range of 4.27±0.07-47.75±0.25μM as compared to the standard drug acarbose. Among the series, compound 7k represented the most potent α-glucosidase inhibitory activity with IC50 values of 4.27±0.07μM. Kinetic analysis revealed that compound 7k is a non-competitive inhibitor with a Ki of 4.43μM. Furthermore, the binding interactions of compound 7k with α-glucosidase was confirmed through molecular docking. This study showed these 1,2,4-triazine derivatives bearing carbazole moiety as a new class of α-glucosidase inhibitors. PMID:27177827

  20. Norsesquiterpenoids and triterpenoids from strawberry cv. Falandi.

    Yang, Dan; Liang, Jian; Xie, Haihui; Wei, Xiaoyi

    2016-07-15

    Falandi is a common strawberry (Fragaria × ananassa Duch.) cultivar in southern China. Further study of the chemical constituents in Falandi fruit led to the isolation of nine norsesquiterpenoids and three triterpenoids. Falandioside D (1) and falandins A (2) and B (3) were new norsesquiterpenoids, and the others excluding tormentic acid (11) were found in strawberry for the first time. Compounds 1 and 11 exhibited potent α-glucosidase inhibitory activity with the half maximal inhibitory concentration (IC50) values of 565.0 and 27.4 μM in comparison to acarbose (619.9 μM). Compounds 3, 7 (blumenol C glucoside), and 11 showed cytotoxicity against human nasopharyngeal carcinoma cell line CNE1 with the IC50 values of 57.6, 56.4, and 36.0 μM, respectively. Among new compounds, 1 showed 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging capacity (IC50=36.2 μM). These results suggested that non-phenolic constituents were also involved in the antidiabetic, antitumour, and antioxidant effects of strawberry fruit. PMID:26948590

  1. In vitro and in vivo comparison of the biological activities of two traditionally and widely used Arum species from Jordan: Arum dioscoridis Sibth & Sm. and Arum palaestinum Boiss.

    Afifi, Fatma U; Kasabri, Violet; Litescu, Simona C; Abaza, Ismail M

    2016-08-01

    Arum dioscoridis and A. palaestinum (Araceae) are indigenous plant species in Jordan. HPLC-MS analysis of A. dioscoridis revealed the presence of apigenin, luteolin, quercetin, quercetin-3-O-β-glucoside, vitexin, isoorientin, esculin, and caffeic and ferulic acids. Both Arum spp., influenced gastrointestinal carbohydrate and lipid digestion and absorption. Orlistat inhibited dose dependently and highly substantially pancreatic lipase (PL) in vitro. Similar to orlistat, Arum species aqueous extracts (AEs), apigenin, caffeic acid and esculin exhibited a concentration related PL inhibition. Comparable to acarbose, dual inhibition of α-amylase/α-glucosidase was observed for both Arum species. Like guar gum, A. dioscoridis AE minimised substantially area under 24 h glucose curve. Acute starch-induced postprandial hyperglycaemia in overnight fasting rats was highly significantly (p < 0.001) decreased by A. dioscoridis AE. A. palaestinum could not perform effectively in either starch- or glucose-fed fasting rats. No antiproliferative effects against colorectal cancer cell lines HT29, HCT116 and SW620 were detected for tested Arum spp. PMID:26284613

  2. Inhibitory Potential of Five Traditionally Used Native Antidiabetic Medicinal Plants on α-Amylase, α-Glucosidase, Glucose Entrapment, and Amylolysis Kinetics In Vitro

    Carene M. N. Picot

    2014-01-01

    Full Text Available Five traditionally used antidiabetic native medicinal plants of Mauritius, namely, Stillingia lineata (SL, Faujasiopsis flexuosa (FF, Erythroxylum laurifolium (EL, Elaeodendron orientale (EO, and Antidesma madagascariensis (AM, were studied for possible α-amylase and α-glucosidase inhibitory property, glucose entrapment, and amylolysis kinetics in vitro. Only methanolic extracts of EL, EO, and AM (7472.92±5.99, 1745.58±31.66, and 2222.96±13.69 μg/mL, resp. were found to significantly (P<0.05 inhibit α-amylase and were comparable to acarbose. EL, EO, AM, and SL extracts (5000 μg/mL were found to significantly (P<0.05 inhibit α-glucosidase (between 87.41±3.31 and 96.87±1.37% inhibition. Enzyme kinetic studies showed an uncompetitive and mixed type of inhibition. Extracts showed significant (P<0.05 glucose entrapment capacities (8 to 29% glucose diffusion retardation index (GDRI, with SL being more active (29% GDRI and showing concentration-dependent activity (29, 26, 21, 14, and 5%, resp.. Amylolysis kinetic studies showed that methanolic extracts were more potent inhibitors of α-amylase compared to aqueous extracts and possessed glucose entrapment properties. Our findings tend to provide justification for the hypoglycaemic action of these medicinal plants which has opened novel avenues for the development of new phytopharmaceuticals geared towards diabetes management.

  3. Isolation and Characterization of an α-Glucosidase Inhibitor from Musa spp. (Baxijiao Flowers

    Zhanwu Sheng

    2014-07-01

    Full Text Available The use of α-glucosidase inhibitors is considered to be an effective strategy in the treatment of diabetes. Using a bioassay-guided fractionation technique, five Bacillus stearothermophilus α-glucosidase inhibitors were isolated from the flowers of Musa spp. (Baxijiao. Using NMR spectroscopy analysis they were identified as vanillic acid (1, ferulic acid (2, β-sitosterol (3, daucosterol (4 and 9-(4′-hydroxyphenyl-2-methoxyphenalen-1-one (5. The half maximal inhibitory concentration (IC50 values of compounds 1–5 were 2004.58, 1258.35, 283.67, 247.35 and 3.86 mg/L, respectively. Compared to a known α-glucosidase inhibitor (acarbose, IC50 = 999.31 mg/L, compounds 3, 4 and 5 showed a strong α-glucosidase inhibitory effect. A Lineweaver-Burk plot indicated that compound 5 is a mixed-competitive inhibitor, while compounds 3 and 4 are competitive inhibitors. The inhibition constants (Ki of compounds 3, 4 and 5 were 20.09, 2.34 and 4.40 mg/L, respectively. Taken together, these data show that the compounds 3, 4 and 5 are potent α-glucosidase inhibitors.

  4. Biologic Propensities and Phytochemical Profile of Vangueria madagascariensis J. F. Gmelin (Rubiaceae: An Underutilized Native Medicinal Food Plant from Africa

    Nelvana Ramalingum

    2014-01-01

    Full Text Available Vangueria madagascariensis (VM, consumed for its sweet-sour fruits, is used as a biomedicine for the management of diabetes and bacterial infections in Africa. The study aims to assess the potential of VM on α-amylase, α-glucosidase, glucose movement, and antimicrobial activity. The antioxidant properties were determined by measuring the FRAP, iron chelating activity, and abilities to scavenge DPPH, HOCl, ∙OH, and NO radicals. Leaf decoction, leaf methanol, and unripe fruit methanol extracts were observed to significantly inhibit α-amylase. Active extracts against α-glucosidase were unripe fruit methanol, unripe fruit decoction, leaf decoction, and ripe fruit methanol, which were significantly lower than acarbose. Kinetic studies revealed a mixed noncompetitive type of inhibition. Leaf methanolic extract was active against S. aureus and E. coli. Total phenolic content showed a strong significant positive correlation (r=0.88 with FRAP. Methanolic leaf extract showed a more efficient NO scavenging potential and was significantly lower than ascorbic acid. Concerning ∙OH-mediated DNA degradation, only the methanol extracts of leaf, unripe fruit, and ripe fruit had IC50 values which were significantly lower than α-tocopherol. Given the dearth of information on the biologic propensities of VM, this study has established valuable primary information which has opened new perspectives for further pharmacological research.

  5. Targeted genome editing in the rare actinomycete Actinoplanes sp. SE50/110 by using the CRISPR/Cas9 System.

    Wolf, Timo; Gren, Tetiana; Thieme, Eric; Wibberg, Daniel; Zemke, Till; Pühler, Alfred; Kalinowski, Jörn

    2016-08-10

    The application of genome editing technologies, like CRISPR/Cas9 for industrially relevant microorganisms, is becoming increasingly important. Compared to other methods of genetic engineering the decisive factor is that CRISPR/Cas9 is relatively easy to apply and thus time and effort can be significantly reduced in organisms, which are otherwise genetically difficult to access. Because of its many advantages and opportunities, we adopted the CRISPR/Cas9 technology for Actinoplanes sp. SE50/110, the producer of the diabetes type II drug acarbose. The functionality of genome editing was successfully shown by the scarless and antibiotic marker-free deletion of the gene encoding the tyrosinase MelC, which catalyzes the formation of the dark pigment eumelanin in the wild type strain. The generated ΔmelC2 mutant of Actinoplanes sp. SE50/110 no longer produces this pigment and therefore the supernatant does not darken. Furthermore, it was shown that the plasmid containing the gene for the Cas9 protein was removed by increasing the temperature due to its temperature-sensitive replication. The precision of the intended mutation was proven and possible off-target effects caused by the genome editing system were ruled out by genome sequencing of several mutants. PMID:27262504

  6. Report from the 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group.

    Schnell, Oliver; Standl, Eberhard; Catrinoiu, Doina; Genovese, Stefano; Lalic, Nebojsa; Skra, Jan; Valensi, Paul; Ceriello, Antonio

    2016-01-01

    The 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held during the annual meeting on 30 October 2015 in Munich. This summit was organized in light of recently published and numerous ongoing CVOTs on diabetes, which have emerged in response to the FDA and the EMA Guidelines. The CVOT Summit stands as a novel conference setup, with the aim of serving as a reference meeting for all topics related to CVOTs in diabetes. Members of the steering committee of the D&CVD EASD Study Group constitute the backbone of the summit. It included presentations of key results on DPP-4 inhibitors, GLP-1-Analogues, SGLT-2 inhibitors, acarbose and insulins. Diabetologists' and cardiologists' perspective on the potential need of new study designs were also highlighted. Furthermore, panel discussions on the design of CVOTs on diabetes were included in the program. The D&CVD EASD Study Group will continue its activity. In-depth discussions and presentations of new CVOTs like LEADER, will be resumed at the 2nd CVOT on diabetes of the D&CVD EASD Study Group, which will be held from 20-22 October 2016 in Munich ( http://www.dcvd.org). PMID:26892706

  7. In vitro hypoglycemic effects of selected dietary fiber sources.

    Ahmed, Faiyaz; Sairam, Sudha; Urooj, Asna

    2011-06-01

    The physiological functions of dietary fiber and its role in health promotion and risk reduction of some chronic diseases has been well documented. In the present investigation, the effect of three dietary fiber sources, oats (OA), barley (BA) and psyllium husk (PH) on glucose adsorption, diffusion and starch hydrolysis were studied using in vitro techniques by simulating gastrointestinal conditions and compared with the commercial dietary fiber sources wheat bran (WB), acarbose (ACB) and guar gum (GG). The glucose binding capacity of all the samples was higher than WB and ACB at 5 mM concentration. In all the samples, the diffusion of glucose was directly proportional to the time and diffusion rate was significantly lower (p ≤ 0.01) in the system containing various samples compared to control. Glucose dialysis retardation index (GDRI) was 100 for OA, BA and PH at 60 min, at 120 min the maximal GDRI was in PH. Whereas; WB and ACB exhibited maximal GDRI at 180 and 240 min. All of these mechanisms might create a concerted function in lowering the rate of glucose absorption and as a result, decrease the postprandial hyperglycemia. PMID:23572748

  8. Screening of minor bioactive compounds from herbal medicines by in silico docking and the trace peak exposure methods.

    Wu, Bin; Song, Hui-Peng; Zhou, Xu; Liu, Xin-Guang; Gao, Wen; Dong, Xin; Li, Hui-Jun; Li, Ping; Yang, Hua

    2016-03-01

    Screening of high potent enzyme inhibitors from herbal medicines is always lacking of efficiency due to the complexity of chemicals. The constituents responsible for the holistic effect may be trace-level chemicals, but these chemicals were covered by highly abundant compositions. To challenge this bottleneck, a strategy for screening minor bioactive compounds was proposed. It generally included four steps, (1) preliminarily find the enzyme binders by ultrafiltration; (2) optimise and predict the potential inhibitors by docking analysis; (3) selectively identify and prepare trace compounds by segment and exposure approach; (4) validate the activity and summarize the structure-activity relationship. As a case study, α-glucosidase (AGH) and Ginkgo biloba extract were used as the experimental materials. By comprehensive screening, 11 trace flavones were screened out and identified as strong AGH inhibitors. Among them, AGH inhibitory activities of syringetin and sciadopitysin were reported for the first time. Their IC50 values were 36.80 and 8.29μM, respectively, which were lower than that of a positive control acarbose. In addition, the AGH inhibitory activities of the flavonoids could be ranked, based on a decreased order, as biflavone, flavone, flavone glycoside, flavone biglycoside. The strategy is expected to be practical and useful for screening bioactive molecules from herbal medicines, especially for the minor compounds, which will definitely accelerate the discovery of new drug candidates. PMID:26852619

  9. Inhibition of key enzymes related to diabetes and hypertension by Eugenol in vitro and in alloxan-induced diabetic rats.

    Mnafgui, Kais; Kaanich, Fatima; Derbali, Amal; Hamden, Khaled; Derbali, Fatma; Slama, Sadok; Allouche, Noureddine; Elfeki, Abdelfattah

    2013-12-01

    The present study investigated the effect of treating diabetic rats with eugenol (EG). In vitro enzyme activity was measured in the presence of eugenol, and it was found to inhibit pancreatic α-amylase (IC(50) = 62.53 µg/mL) and lipase (IC(50) = 72.34 µg/mL) as well as angiotensin converting enzyme (ACE) activity (IC50 = 130.67 µg/mL). In vivo, EG reduced the activity of amylase in serum, pancreas and intestine also the peak level of glucose by 60% compared to diabetic rats. Furthermore, eugenol similar to acarbose reduced serum glycosylated hemoglobin (HbA1c), lipase and ACE levels. In addition, treatments with EG showed notable decrease in serum total-cholesterol, triglycerides and low density lipoprotein-cholesterol levels with an increase of high density lipoprotein-cholesterol. Overall, EG significantly reverted back to near normal the values of the biochemical biomarkers such as transaminases (AST&ALT), alkaline phosphatase (ALP), creatine phosphokinase (CPK) and gamma-glutamyl transpeptidase (GGT) activities, total-bilirubin, creatinine, urea and uric acid rates. PMID:23886079

  10. Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator

    Chen, Yu-Ching; Kok, Victor C; Chien, Ching-Hsuan; Horng, Jorng-Tzong; Tsai, Jeffrey J P

    2015-01-01

    Introduction Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy. Methods We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325) from the 1998–2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223), sulfonylurea (n=3,965), glitazone (n=53), meglitinide (n=128), acarbose (n=150), and insulin (n=806) groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox’s model was used to estimate multivariable hazard ratios (HRs) adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values 0.25 of metformin when compared to lower dose will contribute to a reduction of 80% risk. PMID:26357479

  11. In Vitro and in Vivo Anti-Hyperglycemic Effects of Omija (Schizandra chinensis Fruit

    Young-In Kwon

    2011-02-01

    Full Text Available The entrocytes of the small intestine can only absorb monosaccharides such as glucose and fructose from our diet. The intestinal absorption of dietary carbohydrates such as maltose and sucrose is carried out by a group of a-glucosidases. Inhibition of these enzymes can significantly decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet. Therefore, the inhibitory activity of Omija (Schizandra chinensis extract against rat intestinal a-glucosidase and porcine pancreatic a-amylase were investigated in vitro and in vivo. The in vitro inhibitory activities of water extract of Omija pulp/skin (OPE on a-glucosidase and a-amylase were potent when compared to Omija seeds extract (OSE. The postprandial blood glucose lowering effect of Omija extracts was compared to a known type 2 diabetes drug (Acarbose, a strong a-glucosidase inhibitor in the Sprague-Dawley (SD rat model. In rats fed on sucrose, OPE significantly reduced the blood glucose increase after sucrose loading. Furthermore, the oxygen radical absorbance capacity (ORAC of OSE and OPE was evaluated. OPE had higher peroxyl radical absorbing activity than OSE. These results suggest that Omija, which has high ORAC value with a-glucosidase inhibitory activity and blood glucose lowering effect, could be physiologically useful for treatment of diabetes, although clinical trials are needed.

  12. Structural advantage of sugar beet α-glucosidase to stabilize the Michaelis complex with long-chain substrate.

    Tagami, Takayoshi; Yamashita, Keitaro; Okuyama, Masayuki; Mori, Haruhide; Yao, Min; Kimura, Atsuo

    2015-01-16

    The α-glucosidase from sugar beet (SBG) is an exo-type glycosidase. The enzyme has a pocket-shaped active site, but efficiently hydrolyzes longer maltooligosaccharides and soluble starch due to lower Km and higher kcat/Km for such substrates. To obtain structural insights into the mechanism governing its unique substrate specificity, a series of acarviosyl-maltooligosaccharides was employed for steady-state kinetic and structural analyses. The acarviosyl-maltooligosaccharides have a longer maltooligosaccharide moiety compared with the maltose moiety of acarbose, which is known to be the transition state analog of α-glycosidases. The clear correlation obtained between log Ki of the acarviosyl-maltooligosaccharides and log(Km/kcat) for hydrolysis of maltooligosaccharides suggests that the acarviosyl-maltooligosaccharides are transition state mimics. The crystal structure of the enzyme bound with acarviosyl-maltohexaose reveals that substrate binding at a distance from the active site is maintained largely by van der Waals interactions, with the four glucose residues at the reducing terminus of acarviosyl-maltohexaose retaining a left-handed single-helical conformation, as also observed in cycloamyloses and single helical V-amyloses. The kinetic behavior and structural features suggest that the subsite structure suitable for the stable conformation of amylose lowers the Km for long-chain substrates, which in turn is responsible for higher specificity of the longer substrates. PMID:25451917

  13. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin

    Arumugam Madeswaran

    2014-10-01

    Full Text Available Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selected flavonoids showed binding energy ranging between -6.84 kcal/mol to  -5.96 kcal/mol when compared with that of the standard (-1.97 kcal/mol. Inhibition constant (9.73 µM to 42.76 µM and intermolecular energy (-8.33 kcal/mol to -7.15 kcal/mol of the ligands also coincide with the binding energy.Conclusion: Diosmetin and galangin contributed excellent α-amylase inhibitory activity than the standard because of its structural parameters. These molecular docking analyses of the selected compounds could lead to the further development to find the potent α-amylase inhibitors for the treatment of diabetes.  

  14. Polyketides with α-Glucosidase Inhibitory Activity from a Mangrove Endophytic Fungus, Penicillium sp. HN29-3B1.

    Liu, Yayue; Yang, Qin; Xia, Guoping; Huang, Hongbo; Li, Hanxiang; Ma, Lin; Lu, Yongjun; He, Lei; Xia, Xuekui; She, Zhigang

    2015-08-28

    Five new compounds, pinazaphilones A and B (1, 2), two phenolic compounds (4, 5), and penicidone D (6), together with the known Sch 1385568 (3), (±)-penifupyrone (7), 3-O-methylfunicone (8), 5-methylbenzene-1,3-diol (9), and 2,4-dihydroxy-6-methylbenzoic acid (10) were obtained from the culture of the endophytic fungus Penicillium sp. HN29-3B1, which was isolated from a fresh branch of the mangrove plant Cerbera manghas collected from the South China Sea. Their structures were determined by analysis of 1D and 2D NMR and mass spectroscopic data. Structures of compounds 4 and 7 were further confirmed by a single-crystal X-ray diffraction experiment using Cu Kα radiation. The absolute configurations of compounds 1-3 were assigned by quantum chemical calculations of the electronic circular dichroic spectra. Compounds 2, 3, 5, and 7 inhibited α-glucosidase with IC50 values of 28.0, 16.6, 2.2, and 14.4 μM, respectively, and are thus more potent than the positive control, acarbose. PMID:26230970

  15. Bioactive Natural Products from Piper betle L. Leaves and their α -Glucosidase Inhibitory Potential

    Andreia P. Oliveira

    2016-05-01

    Full Text Available Piper betle L. can be a valuable proposal for the prevention and treatment of several disorders. In fact, i ts leaves are largely consumed as mouth freshener and masticator, being known for their biological properties. This material possesses several kinds of bioactive natural products. Considering that diabetes is a worldwide disease with strong impact on human health, this work intended to explore the in vitro α-glucosidase inhibitory capacity of P. betle leaves, as well as to improve the knowledge on their metabolic pattern. Thus, a targeted metabolite analysis of the aqueous and ethanolic extract was performed by GC-MS, a similar qualitative profile of both extracts being observed. Fourteen metabolites were determined in P. betle leaves, five of them for the first time. Alanine and β-sitosterol were the main amino acid and sterol, respectively. Stearic and palmitic acids were the predominant fatty acids. A strong capacity to inhibit α-glucosidase was noticed, ethanol extract being more active than the positive control (acarbose tested under the same conditions. Taking into account the results obtained, this work further extends the potential application of this herbal medicine, suggesting that its consumption may have a positive impact in the prevention and treatment of diabetes disease.

  16. KAPASITAS ANTIOKSIDAN DAN INHIBITOR ALFA GLUKOSIDASE EKSTRAK UMBI BAWANG DAYAK [Antioxidant and Alpha-Glucosidase Inhibitory Properties of Bawang Dayak Bulb Extracts

    Andi Early Febrinda*

    2013-12-01

    Full Text Available Bawang dayak (Eleutherine palmifolia is an indigenous plant in Borneo traditionally used by Dayak tribes to treat any kind of degenerative deseases including diabetes mellitus. The purpose of this research was to measure antioxidant and antidiabetic capacities of water and ethanolic extracts of bawang dayak bulb. Parameters evaluated in this research were phytochemical screening, total phenolics, flavonoid content, DPPH free-radical scavenging activity, and alpha glucosidase inhibiting (AGI activity. The result showed that the total phenolics and flavonoid content in bawang dayak ethanolic extract (217.71 mg GAE/g and 65.35 mg QE/g were higher than that of the water extract (139.93 mg GAE/g and 16.95 mg QE/g. The ethanolic extract also had higher antioxidant and AGI activities (IC50 112 and 241 ppm than that of the water extract (IC50 526 and 505 ppm. In addition, the IC50 values for AGI in bawang dayak ethanolic extract was lower than acarbose which is known as a commercial antidiabetic agent.

  17. Clinical Observation of 105 Cases with Insulin Glargine Plus Oral Hypoglycemic Drugs for Treating Type 2 Diabetes%甘精胰岛素加口服降糖药治疗2型糖尿病105例临床观察

    刘红丽; 王叶菊

    2011-01-01

    Objective To observe the therapeutic efficacy and safety of insulin glargine plus acarbose on patients with type 2 diabetes with poor efficacy of premixed human insulin in converted. Methods To se-lect105 patients with type 2 diabetic in Hanzhong Central Hospital from 2008 June to 2010 June inpatient, previous use of premixed human insulin 30R, poor glycemic control or hypoglycemia has emerged frequently, conversion of insulin glargine plus acarbose treatment. After 12 weeks,fasting blood glucose( FBG ),2-hour plasma glucose( 2hPG ),hemoglobin A1C( HbAlC )and recorded the incidence rate of hypoglycemia, changes in body mass and insulin dose were observed. Results In98 cases,fasting blood glucose,2-hour plasma glucose, hemoglobin A1C compliance rate was respectively 92% ,87% ,83% ,the incidence of hypoglycemia significantly decreased, insulin dose was reduced, the body mass was not significant changes. Conclusion For patients with poor effect of premixed human insulin in treatment of poor patients," 2 back 1" treatment strategy to provide better glycemic control, and reduce the rate of hypoglycemia.%目的 观察预混人胰岛素疗效不佳的2型糖尿病患者转换甘精胰岛素加阿卡波糖治疗后的疗效及安全性.方法 选取汉中市中心医院2008年6月至2010年6月住院的2型糖尿病患者105例,既往使用预混人胰岛素30R,血糖控制不佳或频繁出现低血糖者,转换甘精胰岛素加阿卡波糖治疗.12周后观察空腹血糖、餐后2 h血糖、糖化血红蛋白,并记录低血糖发生次数、体质量变化及胰岛素剂量.结果 98例患者空腹、餐后2 h血糖、糖化血红蛋白达标率分别是92%、87%、83%,低血糖发生率明显降低,胰岛素剂量较前减少,体质量无明显变化.结论 对于预混人胰岛素治疗欠佳的患者,"2退1"的治疗策略能提供更佳的血糖控制,并减少低血糖的发生率.

  18. Hypoglycaemia after gastric bypass: mechanisms and treatment.

    Ritz, P; Vaurs, C; Barigou, M; Hanaire, H

    2016-03-01

    Hypoglycaemia after gastric bypass can be severe, but is uncommon, and is sometimes only revealed through monitoring glucose concentrations. The published literature is limited by the heterogeneity of the criteria used for diagnosis, arguing in favour of the Whipple triad with a glycaemia threshold of 55 mg/dl as the diagnostic reference. Women who lost most of their excess weight after gastric bypass, long after the surgery was performed, and who did not have diabetes before surgery are at the greatest risk. In this context, hypoglycaemia results from hyperinsulinism, which is either generated by pancreas anomalies (nesidioblastosis) and/or caused by an overstimulation of β cells by incretins, mainly glucagon-like peptide-1 (GLP-1). Glucose absorption is both accelerated and increased because of the direct communication between the gastric pouch and the jejunum. This is a post-surgical exaggeration of a natural adaptation that is seen in patients who have not undergone surgery in whom glucose is infused directly into the jejunum. There is not always a correspondence between symptoms and biological traits; however, hyperinsulinism is constant if hypoglycaemia is severe and there are neuroglucopenic symptoms. The treatment relies firstly on changes in eating habits, splitting food intake into five to six daily meals, slowing gastric emptying, reducing the glycaemic load and glycaemic index of foods, using fructose and avoiding stress at meals. Pharmacological treatment with acarbose is efficient, but other drugs still need to be validated in a greater number of subjects (insulin, glucagon, calcium channel blockers, somatostatin analogues and GLP-1 analogues). Lastly, if the surgical option has to be used, the benefits (efficient symptom relief) and the risks (weight regain, diabetes) should be weighed carefully. PMID:26508374

  19. A comparative study of alpha amylase inhibitory activities of common anti-diabetic plants at Kharagpur 1 block

    Dineshkumar B

    2010-01-01

    Full Text Available In India, the prevalence of diabetes mellitus is on the increase and needs to be addressed appropriately. In this study area, herbal remedies are considered convenient for management of Type 2 diabetes with postprandial hyperglycemia due to their traditional acceptability and availability, low costs, lesser side effects. Comparative evaluation of alpha amylase inhibitory activities of selected plants extracts. Kharagpur is situated in the Midnapur West district of West Bengal in India. In this district, diabetes prevalence is comparatively high. Ten common plants in IIT Kharagpur 1 Block namely, Acalypha indica, Allium cepa, Allium sativum, Azadirachta indica, Musa sapientum, Mangifera indica, Murraya, Ocimum sanctum, Phyllanthus amarus and Tinospora cordifolia were tested for their alpha amylase inhibitory activities to establish anti-diabetic potentials. The plant extracts were prepared sequentially with petroleum ether, hexane, chloroform, ethanol and aqueous. The extracts obtained were subjected to in vitro alpha amylase inhibitory assay using starch azure as a substrate and porcine pancreatic amylase as the enzyme. Statistical difference and linear regression analysis were performed by using Graphpad prism 5 statistical software. Ethanol extracts of Mangifera indica, Azadirachta indica and petroleum ether extract of Murraya koenigii (at a concentrations 10-100μg/ml showed maximum percentage inhibition on alpha amylase activity with an IC 50 value of 37.86 ± 0.32μg/ml, 62.99 ± 1.20μg/ml and 59.0 ± 0.51μg/ml respectively when compared with acarbose (IC 50 value 83.33 ± 0.75μg/ml. The results showing that Mangifera indica, Azadirachta indica and Murraya koenigii might be effective in lowering post prandial hyperglycemia.

  20. Pilot study on the additive effects of berberine and oral type 2 diabetes agents for patients with suboptimal glycemic control

    Di Pierro F

    2012-07-01

    Full Text Available Francesco Di Pierro,1 Nicola Villanova,2 Federica Agostini,2 Rebecca Marzocchi,2 Valentina Soverini,2 Giulio Marchesini21Scientific Department, Velleja Research, Milano, 2Diseases of Metabolism, S Orsola Malpighi Hospital, Bologna, ItalyBackground: Suboptimal glycemic control is a common situation in diabetes, regardless of the wide range of drugs available to reach glycemic targets. Basic research in diabetes is endeavoring to identify new actives working as insulin savers, use of which could delay the introduction of injectable insulin or reduce the insulin dose needed. Commonly available as a nutraceutical, berberine is a potential candidate.Methods and results: Because its low oral bioavailability can be overcome by P-glycoprotein inhibitors like herbal polyphenols, we have tested the nutraceutical combination of Berberis aristata extract and Silybum marianum extract (Berberol® in type 2 diabetes in terms of its additive effect when combined with a conventional oral regimen for patients with suboptimal glycemic control. After 90 days of treatment, the nutraceutical association had a positive effect on glycemic and lipid parameters, significantly reducing glycosylated hemoglobin, basal insulin, homeostatic model assessment of insulin resistance, total and low-density lipoprotein cholesterol, and triglycerides. A relevant effect was also observed in terms of liver function by measuring aspartate transaminase and alanine transaminase. The product had a good safety profile, with distinctive gastrointestinal side effects likely due to its acarbose-like action.Conclusion: Although further studies should be carried out to confirm our data, Berberol could be considered a good candidate as an adjunctive treatment option in diabetes, especially in patients with suboptimal glycemic control.Keywords: berberine, silymarin, glycosylated hemoglobin, diabetes

  1. Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants

    Mohiuddin, M.; Arbain, D.; Islam, A. K. M. Shafiqul; Ahmad, M. S.; Ahmad, M. N.

    2016-02-01

    A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α- d-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau ( Ehretis laevis), Cemumar ( Micromelum pubescens), and Kedondong ( Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C.

  2. In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts.

    Im, Kyung Hoan; Nguyen, Trung Kien; Choi, Jaehyuk; Lee, Tae Soo

    2016-01-01

    Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging activities of T. pubescens methanol (ME) and hot water (HWE) extracts (2.0 mg/mL) were comparable to butylated hydroxytoluene (BHT), the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL) also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC) analysis. The α-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer's disease (AD). The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2-40 μg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced murine macrophage-like cell lines (RAW 264.7) and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities. PMID:27196881

  3. In Vitro Antioxidant, Anti-Diabetes, Anti-Dementia, and Inflammation Inhibitory Effect of Trametes pubescens Fruiting Body Extracts

    Kyung Hoan Im

    2016-05-01

    Full Text Available Trametes pubescens, white rot fungus, has been used for folk medicine in Asian countries to treat ailments such as cancer and gastrointestinal diseases. This study was initiated to evaluate the in vitro antioxidant, anti-diabetes, anti-dementia, and anti-inflammatory activities of T. pubescens fruiting bodies. The 1,1-diphenyl-2-picryl-hydrazyl (DPPH free radical scavenging activities of T. pubescens methanol (ME and hot water (HWE extracts (2.0 mg/mL were comparable to butylated hydroxytoluene (BHT, the positive control. However, the chelating effects of ME and HWE were significantly higher than that of BHT. The HWE (6 mg/mL also showed comparable reducing power to BHT. Eleven phenol compounds were detected by high performance liquid chromatography (HPLC analysis. The α-amylase and α-glucosidase inhibitory activities of the ME and HWE of the mushroom were lower than Acarbose, the standard reference; however, the inhibitory effects of the mushroom extracts at 2.0 mg/mL were moderate. The acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory effects of ME and HWE were moderate and comparable with galanthamine, the standard drug to treat early stages of Alzheimer’s disease (AD. The ME had a neuroprotective effect against glutamate-induced PC-12 cell cytotoxicity at the concentration range of 2–40 μg/mL. The mushroom extracts also showed inflammation inhibitory activities such as production of nitric oxide (NO and expression of inducible nitric oxide synthase (iNOS in lipopolysaccharide (LPS-induced murine macrophage-like cell lines (RAW 264.7 and significantly suppressed the carrageenan-induced rat paw-edema. Therefore, fruiting body extracts of T. pubescens demonstrated antioxidant related anti-diabetes, anti-dementia and anti-inflammatory activities.

  4. Synthesis, X-Ray Crystal Structures, Biological Evaluation, and Molecular Docking Studies of a Series of Barbiturate Derivatives

    Assem Barakat

    2016-01-01

    Full Text Available A series of barbiturates derivatives synthesized and screened for different set of bioassays are described. The molecular structures of compounds 5a, 5d, and 5f were solved by single-crystal X-ray diffraction techniques. The results of bioassay show that compounds 4a, 4b, 4c, 4d, 4e, 4f, and 4g are potent antioxidants in comparison to the tested standards, butylated hydroxytoluene (BHT, and N-acetylcysteine. Compounds 4a–4e (IC50=101.8±0.8–124.4±4.4 μM and 4g (IC50=104.1±1.9 μM were more potent antioxidants than the standard (BHT, IC50=128.8±2.1 μM. The enzyme inhibition potential of these compounds was also evaluated, in vitro, against thymidine phosphorylase, α-glucosidase, and β-glucuronidase enzymes. Compounds 4c, 4h, 4o, 4p, 4q, 5f, and 5m were found to be potent α-glucosidase inhibitors and showed more activity than the standard drug acarbose, whereas compounds 4v, and 5h were found to be potent thymidine phosphorylase inhibitors, more active than the standard drug, 7-deazaxanthine. All barbiturates derivatives (4a–4x, 4z, and 5a–5m were found to be noncytotoxic against human prostate (PC-3, Henrietta Lacks cervical (HeLa and Michigan Cancer Foundation-7 breast (MCF-7 cancer cell lines, and 3T3 normal fibroblast cell line, except 4y which was cytotoxic against all the cell lines.

  5. Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants.

    Mohiuddin, M; Arbain, D; Islam, A K M Shafiqul; Ahmad, M S; Ahmad, M N

    2016-12-01

    A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α-D-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau (Ehretis laevis), Cemumar (Micromelum pubescens), and Kedondong (Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C. PMID:26887579

  6. Diabetes mellitus in dogs and cats: diagnosis and therapy

    Mot, T.,

    2008-12-01

    Full Text Available Diabetes mellitus (DM is a disease of humans and animals, which causes increased levels of blood sugar (glucose. Normally,glucose is brought into the cells by a hormone - insulin.The cells then metabolize glucose to make energy used for all functions of the body. Animals suffering from DM either lack insulin, or the cells cannotuse the insulin that is there. As a result, blood glucose levels increase, and the cells have to use other substances for energy. When blood glucose levels become too high, glucose is found in the urine, causing increased frequency of urination and increased drinking. When blood glucose remains elevated over a period of time, other metabolic changes can occur, such as weight loss, acidosis, seizures, coma, blindness, cataracts, and nerve damage. Animals that are eating normally and not showing signs of illness may only require a blood or urine test to diagnose DM. Concurrent diseases (such as infection, Cushing’s disease, hyperthyroidism, pancreatitis, gastroenteritis, inflammatory bowel disease, hepatic lipidosis, or kidney disease make diabetes more difficult to diagnose and manage. A complete blood screen and other specific tests may be recommended to obtain the diagnosis and baseline values for treatment and future monitoring. The treatment for diabetes in dogs is similar to the treatment for diabetes in humans, through diet and insulin therapy. Dogs and cats with DM are usually treated with insulin. Insulin is a protein and, as such, not suitable for oral administration. Thus, it is administered once or several times daily by the subcutaneous route. Adjustment of the blood glucose concentration demands long hospital care, and subsequently the owner constantly has to keep a strict schedule at home. In veterinary practice the main groups of oral antidiabetic (used in human medicine either are: carbohydrate absorption inhibitors (e.g. acarbose; insulin sensitisers (biguanides such as metformin, thiazolidinedions

  7. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents

    Sonia A Tucci

    2010-05-01

    Full Text Available Sonia A Tucci, Emma J Boyland, Jason CG HalfordKissileff Laboratory for the Study of Human Ingestive Behaviour, School of Psychology, University of Liverpool, Liverpool, UKAbstract: Obesity is a global epidemic associated with significant morbidity and mortality in adults and ill health in children. A proven successful approach in weight management has been the disruption of nutrient digestion, with orlistat having been used to treat obesity for the last 10 years. Although orlistat-induced weight loss remains modest, it produces meaningful reductions in risk factors for obesity-related conditions such as diabetes and cardiovascular disease. Moreover, this lipase inhibitor is free of the serious side effects that have dogged appetite-suppressing drugs. This success had driven investigation into new generation nutraceuticals, supplements and pharmaceutical agents that inhibit the breakdown of complex carbohydrates and fats within the gut. This review focuses on agents purported to inhibit intestinal enzymes responsible for macronutrient digestion. Except for some synthetic products, the majority of agents reviewed are either botanical extracts or bacterial products. Currently, carbohydrate digestion inhibitors are under development to improve glycemic control and these may also induce some weight loss. However, colonic fermentation induced side effects, such as excess gas production, remain an issue for these compounds. The α-glucosidase inhibitor acarbose, and the α-amylase inhibitor phaseolamine, have been used in humans with some promising results relating to weight loss. Nonetheless, few of these agents have made it into clinical studies and without any clinical proof of concept or proven efficacy it is unlikely any will enter the market soon.Keywords: lipase, amylase, saccharidases, overweight, orlistat, Alli®, digestion, body weight

  8. Medical management of clomiphene-resistant polycystic ovarian syndrome: an update

    Sharonjeet Kaur

    2014-02-01

    Full Text Available Clomiphene citrate is the traditional first-line treatment for chronic anovulation that characterizes polycystic ovary syndrome (PCOS. A gold standard therapy has always been Clomiphene Citrate (CC. However, 20%-25% of PCOS women fail to ovulate with incremental doses of CC. A good body of evidence suggest that alternatives for PCOS women with CC-resistant anovulation include insulin sensitizers like metformin and pioglitazone. Insulin sensitizers improves pregnancy outcome and ovulation rate by and acts by ameliorating insulin sensitivity and hyperandrogenemia. Metformin is preferred in obese women. Gonadotropins induce ovulation and maintain optimal follicle growth via controlled administration of follicle stimulation hormone. Two regimens are used which includes high and low dose regimen. Low dose regimen is preferred but is associated adverse effects like ovarian hyperstimulation syndrome (OHSS and increased cost. Extending clomiphene therapy reduces cost and improves pregnancy outcome. Glucocorticoids are preferably used when serum Dehydroepiandrosterone levels are > 200µg/dL. Bromocriptine improves ovulation rate by decreasing prolactin levels. Human Chorionic Gonadotropin restores ovulation but its use is limited during intrauterine insemination. Tamoxifen acts in a similar way as CC but has lesser antiestrogenic effect on the endometrium, cervical mucus, and granulosa cells, hence an added advantage of monofollicular ovulation. Aromatase inhibitors block conversion androstenedione and testosterone to estrogen in ovary and improves ovulation rate. Added advantage includes lesser cost, simple to use, no danger of multiple pregnancies and convenient for patient. Combination of GnRH analogues and Gonadotropins are associated with increased risk of OHSS. D-chiro-inositol, N-Acetylcysteine, melatonin and acarbose are tried with little success. [Int J Basic Clin Pharmacol 2014; 3(1.000: 1-9

  9. Drug Promiscuity in PDB: Protein Binding Site Similarity Is Key.

    V Joachim Haupt

    Full Text Available Drug repositioning applies established drugs to new disease indications with increasing success. A pre-requisite for drug repurposing is drug promiscuity (polypharmacology - a drug's ability to bind to several targets. There is a long standing debate on the reasons for drug promiscuity. Based on large compound screens, hydrophobicity and molecular weight have been suggested as key reasons. However, the results are sometimes contradictory and leave space for further analysis. Protein structures offer a structural dimension to explain promiscuity: Can a drug bind multiple targets because the drug is flexible or because the targets are structurally similar or even share similar binding sites? We present a systematic study of drug promiscuity based on structural data of PDB target proteins with a set of 164 promiscuous drugs. We show that there is no correlation between the degree of promiscuity and ligand properties such as hydrophobicity or molecular weight but a weak correlation to conformational flexibility. However, we do find a correlation between promiscuity and structural similarity as well as binding site similarity of protein targets. In particular, 71% of the drugs have at least two targets with similar binding sites. In order to overcome issues in detection of remotely similar binding sites, we employed a score for binding site similarity: LigandRMSD measures the similarity of the aligned ligands and uncovers remote local similarities in proteins. It can be applied to arbitrary structural binding site alignments. Three representative examples, namely the anti-cancer drug methotrexate, the natural product quercetin and the anti-diabetic drug acarbose are discussed in detail. Our findings suggest that global structural and binding site similarity play a more important role to explain the observed drug promiscuity in the PDB than physicochemical drug properties like hydrophobicity or molecular weight. Additionally, we find ligand

  10. Heart Failure Considerations of Antihyperglycemic Medications for Type 2 Diabetes.

    Standl, Eberhard; Schnell, Oliver; McGuire, Darren K

    2016-05-27

    Prevalent and incident heart failure (HF) is increased in people with type 2 diabetes mellitus, with risk directly associated with the severity of hyperglycemia. Furthermore, in patients with type 2 diabetes mellitus, mortality is increased ≈10-fold in patients with versus without HF. Reducing HF with antihyperglycemic therapies, however, has been unsuccessful until recently. In fact, HF as an important outcome in patients with type 2 diabetes mellitus seems to be heterogeneously modulated by antihyperglycemic medications, as evidenced by results from cardiovascular outcome trials (CVOTs) and large observational cohort studies. Appropriately powered and executed CVOTs are necessary to truly evaluate cardiovascular safety and efficacy of new antihyperglycemic medications, as reflected by the guidance of the US Food and Drug Administration and other regulatory agencies since 2008. In light of the best available evidence at present, metformin and the sodium-glucose-co-transporter 2-inhibitor empagliflozin seem to be especially advantageous with regard to HF effects, with their use associated with reduced HF events and improved mortality. Acarbose, the dipeptidyl-peptidase 4-inhibitor sitagliptin, the glucagon-like peptide 1-receptor agonist lixisenatide based on presently available CVOT results comprise reasonable additional options, as significant harm in terms of HF has been excluded for those drugs. Additions to this list are anticipated pending results of ongoing CVOTs. Although no HF harm was seen in CVOTs for insulin or sulfonylureas, they should be used only with caution in patients with HF, given their established high risk for hypoglycemia and some uncertainties on their safety in patients with HF derived from epidemiological observations. Pioglitazone is contraindicated in patients with HF>New York Heart Association I, despite some benefits suggested by CVOT subanalyses. PMID:27230644

  11. Effect of lipid extracts of Nigella sativa L. seeds on the liver ATP reduction and alpha-glucosidase inhibition.

    Sobhi, Widad; Stevigny, Caroline; Duez, Pierre; Calderon, Bedro Buc; Atmani, Djebbar; Benboubetra, Mustapha

    2016-01-01

    Various extracts from the seeds of Nigella sativa have been used in traditional folk medicine to treat inflammation, liver disorders and arthritis. These seeds have been experimentally shown to possess antioxidant and hepatoprotective properties. Beside the hypoglycaemic and hypolipidemic effects, this study was carried out to evaluate, in vitro, toxicological effect of lipid extracts from the Nigella sativa seeds. The tested fractions were: (i) defatted methanolic extract, (ii) total lipid extract obtained by hexane extraction from methanolic extract and (iii) neutral and polar lipid fractions. The fractions were assessed, in vitro, for their inhibitory activity potential on the enzyme alpha-glucosidase as suppressing the enzyme activity is one among the therapeutic approaches to attenuate postprandial hyperglycemia. High inhibition of alpha-glucosidase by the two polar lipid fractions (F6 and F7) was reflected by their IC50 (0.51±0.04mg/ml and 0.55±0.09mg/ml, respectively), compared to acarbose (0.53±0.06mg/ml) and thymoquinone (0.65±0.05mg/ml). The hypoglycaemic effect of the polar lipid fraction of Nigella sativa could be explained by the inhibition of alpha-glucosidase, which is one of early steps of carbohydrate metabolism. Toxicological evaluation was investigated on precision-cut rat liver slices (PCLS). On PCLS, lipid extracts reduced ATP levels by 27 to 35%. Results indicate suggest that Nigella sativa extracts don't show a hepatoprotective effect against acetaminophen, but don't exhibit a major hepatotoxicity when tested alone. PMID:26826824

  12. Influence of Total Anthocyanins from Bitter Melon (Momordica charantia Linn.) as Antidiabetic and Radical Scavenging Agents.

    Güdr, Aytaç

    2016-01-01

    The majority of the antioxidant and antidiabetic activities of fruits are anthocyanins; a group of polyphenolics that are responsible for the color of many fruits, vegetables and flowers. The harvesting time, storage conditions, maturity, extraction steps etc. are very important for the biological activities based on the alteration of chemical composition. The free radical scavenging and antidiabetic activities of total anthocyanins from bitter melon (Momordica charantia Linn) fruit (TAMC) were evaluated by considering four harvesting times. The free radical scavenging activities of the TAMC samples were assessed using DPPH(•), DMPD(•+) and ABTS(•+) assays against BHA, rutin and trolox standards. September as a harvesting period (TAMC-S) had effective DPPH(•) (SC50 2.55 ± 0.08 μg/mL), DMPD(•+) (SC50 2.68 ± 0.09 μg/mL) and ABTS(•+) (SC50 8.19 ± 0.09 μg/mL) scavenging activities compared with other samples and standards. In addition, August (TAMC-A) as a harvesting period showed very influential inhibitory activity against α-amylase (IC50 56.86 ± 1.12 μg/mL) and moderate inhibitory activity against α-glucosidase (IC50 88.19 ± 0.74 μg/mL). In comparison, pharmaceutical active ingredients such as acarbose exhibited anti-amylase and anti-glucosidase activities with IC50 values of 93.07 ± 1.49 μg/mL and 77.25 ± 1.20 μg/mL respectively. These results suggest that the correct selection of harvest period can significantly increase anthocyanin quantity because of the pharmaceutic properties of TAMC. Consequently, TAMC may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia that can be also used as food additives due to its antiradical activity. PMID:27610171

  13. Enzyme Inhibitory Properties, Antioxidant Activities, and Phytochemical Profile of Three Medicinal Plants from Turkey

    Gokhan Zengin

    2015-01-01

    Full Text Available We aimed to investigate the inhibitory potential of three medicinal plants (Hedysarum varium, Onobrychis hypargyrea, and Vicia truncatula from Turkey against key enzymes involved in human pathologies, namely, diabetes (α-amylase and α-glucosidase, neurodegenerative disorders (tyrosinase, acetylcholinesterase, and butyrylcholinesterase, and hyperpigmentation (tyrosinase. The antioxidant potential, phenolic and flavonoid content of ethyl acetate, and methanolic and aqueous extracts were investigated using in vitro assays. The total antioxidant capacity (TAC, β-carotene/linoleic acid bleaching activity, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH•, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+, cupric ion reducing antioxidant capacity (CUPRAC, ferric reducing antioxidant power (FRAP, and metal chelating activity on ferrous ions were used to evaluate the antioxidant capabilities of the extracts. The half-maximal inhibitory concentrations (IC50 of the extracts on cholinesterase, tyrosinase, and α-amylase were significantly higher than the references, galantamine, kojic acid, and acarbose, respectively. The half-maximal effective concentrations (EC50 of the extracts on TAC, CUPRAC, and FRAP were significantly higher than trolox. The phenol and flavonoid contents of the plant extracts were in the range 20.90±0.190–83.25±0.914 mg gallic acid equivalent/g extract and 1.45±0.200–39.71±0.092 mg rutin equivalent/g extract, respectively. The plants were found to possess moderate antioxidant capacities and interesting inhibitory action against key enzymes.

  14. Effects of carbohydrase-inhibiting compounds on in vitro rumen fermentation

    Giorgio Marchesini

    2014-08-01

    Full Text Available Batch culture fermentations with ruminal content were conducted to determine the effects of plant-derived [bilberry extract (BBE, phaseolamin, white mulberry (WMB, common flax] carbohydrase-inhibiting compounds on microbial fermentation. The cultures with these compounds, at two different doses (15 and 150 mg, were compared with both acarbose (ACB and batch cultures without the addition of any enzyme-inhibiting compounds (Control. Incubations were conducted in triplicate and replicated. The pH, volatile fatty acids, ammonia N, apparent dry matter (DMD and starch disappearance were measured after 5 and 24 h of incubation. Treatment with ACB, after 5 h, significantly reduced maize meal fermentation, resulting in the highest pH levels (P<0.01, the lowest total VFA concentration (P=0.01 and the lowest DMD (P<0.01. On the opposite, BBE and WMB caused the highest drop in pH, due to the rapid fermentation of their sugar content. Treatment with BBE resulted in an increase in propionate and in an apparently low ammonia N concentration, whilst ACB (150 mg led to the highest values of acetate (P<0.05 and to a relative high concentration of ammonia N. After 24 h the differences in the fermentation pattern among supplements remained similar to those found after 5 h. In addition, BBE showed an activity against starch degradation, although this effect was concealed by the fermentation of sugars present in that supplement. These results show that some compounds modify the fermentation pattern of the substrate, but further studies are needed to clarify their impact on the complex rumen microbial community.

  15. Synthesis and structure investigation of novel pyrimidine-2,4,6-trione derivatives of highly potential biological activity as anti-diabetic agent

    Barakat, Assem; Soliman, Saied M.; Al-Majid, Abdullah Mohammed; Lotfy, Gehad; Ghabbour, Hazem A.; Fun, Hoong-Kun; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

    2015-10-01

    Synthesis of (±)-1,3-dimethyl-5-(1-(3-nitrophenyl)-3-oxo-3-phenylpropyl)pyrimidine-2,4,6(1H,3H,5H)-trione (3) is reported. The structure of compound 3 was deduced by using spectroscopic methods, X-ray crystallography, and DFT calculations. The calculated geometric parameters were found to be in good agreement with the experimental data obtained from the X-ray structure. The NBO calculations were performed to predict the natural atomic charges at the different atomic sites and to study the different intramolecular charge transfer (ICT) interactions. The high LP(3)O6 →z BD*(2)O5-N3 ICT interaction energy (165.36 kcal/mol) indicated very strong n → π* electron delocalization while the small LP(2)O → BD*(1)C-H ICT interaction energies indicated that the C-H … O intramolecular interactions are weak. The 1H and 13C NMR chemical shifts calculated using GIAO method showed good agreement with the experimental data. The calculated electronic spectra of the studied compound using TD-DFT method showed intense electronic transition band at 243.9 nm (f = 0.2319) and a shoulder at 260.2 nm (f = 0.1483) which were due to H-4/H-2/H-1/H → L+2 and H-5 → L electronic excitations, respectively. Compound 3 (IC50 = 305 ± 3.8 μM) was identified as a potent inhibitor of α-glucosidase in vitro and showed several fold more inhibition than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Molecular docking of the synthesized compound was discussed.

  16. Bioactive 30-Noroleanane Triterpenes from the Pericarps of Akebia trifoliata

    Jing Wang

    2014-04-01

    Full Text Available Two new 30-noroleanane triterpenes, 2α,3β,20α-trihydroxy-30-norolean-12-en-28-oic acid (1, 2α,3β-dihydroxy-23-oxo-30-norolean-12,20(29-dien-28-oic acid (2, were isolated from the pericarps of Akebia trifoliata, together with four known ones, 3β-akebonoic acid (3, 2α,3β-dihydroxy-30-noroleana-12,20(29-dien-28-oic acid (4, 3α-akebonoic acid (5 and quinatic acid (6. Their structures were established on the basis of detailed spectroscopic analysis, and they were all isolated from the pericarps of A. trifoliata for the first time. Compounds 3−6 showed in vitro bacteriostatic activity against four assayed Gram-positive bacterial strains. In particular 3 showed antibacterial activity toward MRSA with a MIC value 25 μg/mL, which was more potent than kanamycin (MIC 125 μg/mL. No compounds showed antibacterial activity toward the three Gram-negative bacteria tested. Compounds 4 and 5 showed interesting in vitro growth inhibitory activity against human tumor A549 and HeLa cell lines, with IC50 values ranging from 8.8 and 5.6 μM, respectively. Compounds 1, 2, 5 and 6 were further revealed to show significant in vitro α-glucosidase inhibitory activity with IC50 values from 0.035 to 0.367 mM, which were more potent than the reference compound acarbose (IC50 0.409 mM.

  17. A fluorescence resonance energy transfer (FRET) based "Turn-On" nanofluorescence sensor using a nitrogen-doped carbon dot-hexagonal cobalt oxyhydroxide nanosheet architecture and application to α-glucosidase inhibitor screening.

    Li, Guoliang; Kong, Weiheng; Zhao, Mei; Lu, Shuaimin; Gong, Peiwei; Chen, Guang; Xia, Lian; Wang, Hua; You, Jinmao; Wu, Yongning

    2016-05-15

    The medicines targeted at α-glucosidase played an important role in anti-diabetes and anti-HIV therapy. Unfortunately, the method based on fluorescent assay strategy for α-glucosidase inhibitor screening remains poorly investigated. In this study, a novel "Turn On" fluorescence sensor platform has been developed for trace α-glucosidase inhibitor screening from natural medicines. Firstly, carbon dots were prepared by one-pot synthesis and used as the signal output. Combining with the carbon dots, cobalt oxyhydroxide (CoOOH) nanoflakes were employed to build the fluorescence resonance energy transfer (FRET) based sensor platform. Secondly, L-ascorbic acid-2-O-α-D-glucopyranosyl (AAG) was innovatively introduced as α-glucosidase substrate. With hydrolysis of AAG by α-glucosidase, ascorbic acids (AA) were released that can rapidly reduce CoOOH nanoflakes to Co(2+), and then FRET was stopped accompanying with the fluorescence recovery of CDs. The sensor platform was ultrasensitive to AA with a detection limit of 5nM, ensuring the sensitive monitoring of enzyme activity. Acarbose was used as the inhibitor model and its inhibition rate is proportional to the logarithm of concentration in range of 10(-9)-10(-3)M with the correlation coefficient of R(2)=0.996, and an ultralow limit of detection of ~1×10(-9)M was obtained. The inhibiting ability of seven compounds isolated from natural medicines was also evaluated. The constructed sensor platform was proven to be sensitive and selective as well as cost-effective, facile and reliable, making it promising as a candidate for trace α-glucosidase inhibitor screening. PMID:26774085

  18. Composition and Biological Activity of Volatile Oil from Salviajudaica and S. multicaulis from Jordan.

    Afifi, Fatma U; Kasabri, Violet; Al-Jaber, Hala I; Abu-Irmaileh, Barakat E; Al-Qudah, Mahmoud A; Abazaa, Ismail F

    2016-04-01

    The aim of this work was to determine the composition of the hydro-distilled essential oil of Salvia judaica Boiss. and S. multicaulis Vahl. (Lamiaceae) from Jordan by GC and GC-MS and to report the actual composition of their fresh leaves and flowers using SPME (Solid Phase Micro-Extraction).Their dual alpha-amylase/alpha glucosidase and pancreatic lipase inhibitory activities as well as their anti-proliferative potential were screened. The aroma profile of the leaves, flowers, and flowers at pre-flowering stages of S. judaica, obtained through SPME was composed of sesquiterpene hydrocarbons (87.7 %, 71.8 %, and 86.2 %, respectively) while the hydro-distilled oil of the dry leaves was rich in oxygenated sesquiterpenes (50.8%). Fresh leaves of S. multicaulis were rich in oxygenated monoterpenes (58.1%), while monoterpene hydrocarbons dominated the blooming flowers (57.2%) and the flowers at the pre-flowering stage (64.7%). The hydro-distilled oil of the dry leaves was rich in oxygenated monoterpenes (77.6%). With doxorubicin as a positive control, no anti-proliferative activity was observed against colorectal cancer cell lines HT29, HCT116, and SW620 using SRB assay for either Salvia spp. In vitro enzymatic starch digestion was evaluated with Acarbose (IC50: 0.2 ± 0.0 µg /mL) as the reference drug. The respective IC50 (mg/mL) values of S. judaica and S. multicaulis aqueous extracts were 4.9 ± 0.4 and 10.3 ± 0.9. Modulation of pancreatic lipase activity (PL) was determined by colorimetry and compared with Orlistat (IC50 : 0.11 ± 0.0 µg/mL). PL-IC50 values (µg/mL) obtained for S. judaica and S. multicaulis were 108.5±6.4 and 31.8 ± 0.8, respectively. PMID:27396212

  19. Synthesis of novel flavone hydrazones: in-vitro evaluation of α-glucosidase inhibition, QSAR analysis and docking studies.

    Imran, Syahrul; Taha, Muhammad; Ismail, Nor Hadiani; Kashif, Syed Muhammad; Rahim, Fazal; Jamil, Waqas; Hariono, Maywan; Yusuf, Muhammad; Wahab, Habibah

    2015-11-13

    Thirty derivatives of flavone hydrazone (5-34) had been synthesized through a five-step reaction and screened for their α-glucosidase inhibition activity. Chalcone 1 was synthesized through aldol condensation then subjected through oxidative cyclization, esterification, and condensation reaction to afford the final products. The result for baker's yeast α-glucosidase (EC 3.2.1.20) inhibition assay showed that all compounds are active with reference to the IC50 value of the acarbose (standard drug) except for compound 3. Increase in activity observed for compounds 2 to 34 clearly highlights the importance of flavone, hydrazide and hydrazone linkage in suppressing the activity of α-glucosidase. Additional functional group on N-benzylidene moiety further enhances the activity significantly. Compound 5 (15.4 ± 0.22 μM), a 2,4,6-trihydroxy substituted compound, is the most active compound in the series. Other compounds which were found to be active are those having chlorine, fluorine, and nitro substituents. Compounds with methoxy, pyridine, and methyl substituents are weakly active. Further studies showed that they are not active in inhibiting histone deacetylase activity and do not possess any cytotoxic properties. QSAR model was being developed to further identify the structural requirements contributing to the activity. Using Discovery Studio (DS) 2.5, various 2D descriptors were being used to develop the model. The QSAR model is able to predict the pIC50 and could be used as a prediction tool for compounds having the same skeletal framework. Molecular docking was done for all compounds using homology model of α-glucosidase to identify important binding modes responsible for inhibition activity. PMID:26491979

  20. The maltodextrin transport system and metabolism in Lactobacillus acidophilus NCFM and production of novel alpha-glucosides through reverse phosphorolysis by maltose phosphorylase.

    Nakai, Hiroyuki; Baumann, Martin J; Petersen, Bent O; Westphal, Yvonne; Schols, Henk; Dilokpimol, Adiphol; Hachem, Maher A; Lahtinen, Sampo J; Duus, Jens Ø; Svensson, Birte

    2009-12-01

    A gene cluster involved in maltodextrin transport and metabolism was identified in the genome of Lactobacillus acidophilus NCFM, which encoded a maltodextrin-binding protein, three maltodextrin ATP-binding cassette transporters and five glycosidases, all under the control of a transcriptional regulator of the LacI-GalR family. Enzymatic properties are described for recombinant maltose phosphorylase (MalP) of glycoside hydrolase family 65 (GH65), which is encoded by malP (GenBank: AAV43670.1) of this gene cluster and produced in Escherichia coli. MalP catalyses phosphorolysis of maltose with inversion of the anomeric configuration releasing beta-glucose 1-phosphate (beta-Glc 1-P) and glucose. The broad specificity of the aglycone binding site was demonstrated by products formed in reverse phosphorolysis using various carbohydrate acceptor substrates and beta-Glc 1-P as the donor. MalP showed strong preference for monosaccharide acceptors with equatorial 3-OH and 4-OH, such as glucose and mannose, and also reacted with 2-deoxy glucosamine and 2-deoxy N-acetyl glucosamine. By contrast, none of the tested di- and trisaccharides served as acceptors. Disaccharide yields obtained from 50 mmbeta-Glc 1-P and 50 mm glucose, glucosamine, N-acetyl glucosamine, mannose, xylose or l-fucose were 99, 80, 53, 93, 81 and 13%, respectively. Product structures were determined by NMR and ESI-MS to be alpha-Glcp-(1-->4)-Glcp (maltose), alpha-Glcp-(1-->4)-GlcNp (maltosamine), alpha-Glcp-(1-->4)-GlcNAcp (N-acetyl maltosamine), alpha-Glcp-(1-->4)-Manp, alpha-Glcp-(1-->4)-Xylp and alpha-Glcp-(1-->4)- L-Fucp, the three latter being novel compounds. Modelling using L. brevis GH65 as the template and superimposition of acarbose from a complex with Thermoanaerobacterium thermosaccharolyticum GH15 glucoamylase suggested that loop 3 of MalP involved in substrate recognition blocked the binding of candidate acceptors larger than monosaccharides. PMID:19919544

  1. Diabetes: insulin resistance and derangements in lipid metabolism. Cure through intervention in fat transport and storage.

    Raz, Itamar; Eldor, Roi; Cernea, Simona; Shafrir, Eleazar

    2005-01-01

    of the compliant application of drastic lifestyle change comprising both diet and exercise and pharmacotherapy that reduces mesenteric fat mass and activity. The first step should be an attempt to effectively induce a lifestyle change. Next comes pharmacotherapy including acarbose, metformin, PPARgamma, or PPARgammaalpha agonists, statins and orlistat, estrogens in postmenopausal women or testosterone in men. Among surgical procedures, gastric bypass has been proven to produce beneficial results in advance of other surgical techniques, the evidence basis of which still needs strengthening. PMID:15386813

  2. Selected Tea and Tea Pomace Extracts Inhibit Intestinal α-Glucosidase Activity in Vitro and Postprandial Hyperglycemia in Vivo

    Jungbae Oh

    2015-04-01

    Full Text Available Type 2 diabetes mellitus (T2DM is a metabolic disorder characterized by postprandial hyperglycemia, which is an early defect of T2DM and thus a primary target for anti-diabetic drugs. A therapeutic approach is to inhibit intestinal α-glucosidase, the key enzyme for dietary carbohydrate digestion, resulting in delayed rate of glucose absorption. Although tea extracts have been reported to have anti-diabetic effects, the potential bioactivity of tea pomace, the main bio waste of tea beverage processing, is largely unknown. We evaluated the anti-diabetic effects of three selected tea water extracts (TWE and tea pomace extracts (TPE by determining the relative potency of extracts on rat intestinal α-glucosidase activity in vitro as well as hypoglycemic effects in vivo. Green, oolong, and black tea bags were extracted in hot water and the remaining tea pomace were dried and further extracted in 70% ethanol. The extracts were determined for intestinal rat α-glucosidases activity, radical scavenging activity, and total phenolic content. The postprandial glucose-lowering effects of TWE and TPE of green and black tea were assessed in male Sprague-Dawley (SD rats and compared to acarbose, a known pharmacological α-glucosidase inhibitor. The IC50 values of all three tea extracts against mammalian α-glucosidase were lower or similar in TPE groups than those of TWE groups. TWE and TPE of green tea exhibited the highest inhibitory effects against α-glucosidase activity with the IC50 of 2.04 ± 0.31 and 1.95 ± 0.37 mg/mL respectively. Among the specific enzymes tested, the IC50 values for TWE (0.16 ± 0.01 mg/mL and TPE (0.13 ± 0.01 mg/mL of green tea against sucrase activity were the lowest compared to those on maltase and glucoamylase activities. In the animal study, the blood glucose level at 30 min after oral intake (0.5 g/kg body wt of TPE and TWE of both green and black tea was significantly reduced compared to the control in sucrose-loaded SD

  3. 抗糖尿病药物的临床用药分析%Analysis of the usage of anti-diabetes drugs

    李旭; 何晶; 韩莹旻; 邹明

    2011-01-01

    Objective To analyze the clinical application status of anti-diabetes agent used in our hospital, and to provide reference for clinical application. Methods The anti-diabetes drugs variety, amount and the frequency of drug usage and other data from 2007 to 2009, were statistically analyzed using internet methods. Results The sales revenue of the anti-diabetes drugs increased from year to year, and its sales proportion among all drugs in the hospital was gradually increasing at the same time. The sales revenue of the insulin-type drugs was the largest and increased every year. Acarbose, metformin and glimepiride were the main oral anti-diabetes drugs in our hospital. Conclusions Anti-diabetes drugs have big market potential. The drugs that are safe, effective with good compliance and moderate prices are the majority of diabetes-treating drugs.%目的 分析医院抗糖尿病药物的使用情况,为临床合理用药提供依据.方法 运用医院药库计算机网络系统对我院2007-2009年所用的抗糖尿病药物品种、金额和用药频度等数据进行统计学分析.结果 抗糖尿病药物的销售金额呈逐年上升趋势,在我院药物总销售金额所占比例逐渐增加.其中胰岛素类药物在所有抗糖尿病药物的销售中占有率最大,3年的销售金额分别为30.21万元、126.93和246.58万元.阿卡波糖、二甲双胍和格列美脲是我院使用的主要口服抗糖尿病药物.结论 糖尿病的致病因素很多,主要和胰岛素分泌或生成异常有关.抗糖尿病药物市场潜力大,安全、有效、依从性好、价格适中的药物是糖尿病治疗药物的必然发展趋势.

  4. 医院2012-2014年口服降糖药物利用分析%Use analysis of oral hypoglycemic drugs in hospital from 2012 to 2014

    王燕平; 张琳

    2015-01-01

    目的 评价北京军区总医院口服降糖药的应用情况.方法 采用限定日剂量(DDD)分析方法,对北京军区总医院2012-2014年口服降糖药的用药频度、销售金额等数据进行统计、分析.结果 口服降糖药的用药频度逐年增长(2012-2014年依次为:1 874 755、1 913 100、2 233 570),销售金额呈增长趋势(2012-2014年依次为:1 073.42、1 027.66、1 324.25万元).用药频度和销售金额排序前3位的药品为阿卡波糖、二甲双胍、格列美脲;销售金额排序与用药频度排序的比值均为1.00.结论 本院门诊患者口服降糖药的使用基本合理.%Objective To analyze the use of oral hypoglycemic drugs in Beijing Military Region General Hospital of Chinese People' s Liberation Army.Methods The data of frequency of drug use (DDDs),sale account of oral hypoglycemic drugs in Beijing Military Region General Hospital of Chinese People's Liberation Army from 2012 to 2014 were retrospectively analyzed.Results The DDDs of oral hypoglycemic drugs increased year by year (2012:1 874 755,2013:1 913 100,2014:2 233 570),the sale account were keep increasing (2012:10.734 2 million yuan,2013:10.276 6 million yuan,2014:13.242 5 million yuan).Acarbose,metformin and glimepiride ranked top 3 for both DDDs and sale account,their rank ratio of DDDs/sale account were all 1.00.Conclusion The use of hypoglycemic drugs in our hospital is rational on the whole.

  5. Antimicrobial and selected in vitro enzyme inhibitory effects of leaf extracts, flavonols and indole alkaloids isolated from Croton menyharthii.

    Aderogba, Mutalib A; Ndhlala, Ashwell R; Rengasamy, Kannan R R; Van Staden, Johannes

    2013-01-01

    Croton species are used in folk medicine in the management of infections, inflammation and oxidative stress-related diseases. In order to isolate, characterize and evaluate the bioactive constituents of Croton menyharthii Pax leaf extracts, repeated column fractionation of the ethyl acetate fraction from a 20% aqueous methanol crude extract afforded three flavonols identified by NMR (1D and 2D) spectroscopic methods as myricetrin-3-O-rhamnoside (myricetrin, 1), quercetin-3-O-rhamnoside (2) and quercetin (3) along with an indole alkaloid, (E)-N-(4-hydroxycinnamoyl)-5-hydroxytryptamine, [trans-N-(p-coumaroyl) serotonin, 4]. All the compounds are reported from the leaf extract of this plant for the first time. The crude extracts, four solvent fractions (hexane, DCM, ethyl acetate and butanol) and isolated compounds obtained from the leaves were evaluated for their inhibitory effects on selected bacteria, a fungus (Candida albicans), cyclooxygenase (COX-2), α-glucosidase and acetylcholinesterase (AChE). Amongst the compounds, quercetin (3) was the most active against Bacillus subtilis and Candida albicans while myricetrin-3-O-rhamnoside (1) and trans-N-(p-coumaroyl) serotonin (4) were the most active compounds against Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The inhibitory activity of myricetrin-3-O-rhamnoside (1) against COX-2 was insignificant while that of the other three compounds 2-4 was low. The AChE inhibitory activity of the alkaloid, trans-N-(p-coumaroyl) serotonin was high, with a percentage inhibitory activity of 72.6% and an IC50 value of 15.0 µg/mL. The rest of the compounds only had moderate activity. Croton menyharthii leaf extracts and isolated compounds inhibit α-glucosidase at very low IC50 values compared to the synthetic drug acarbose. Structure activity relationship of the isolated flavonols 1-3 is briefly outlined. Compounds 1-4 and the leaf extracts exhibited a broad spectrum of activities. This validates the

  6. Antimicrobial and Selected In Vitro Enzyme Inhibitory Effects of Leaf Extracts, Flavonols and Indole Alkaloids Isolated from Croton menyharthii

    Johannes Van Staden

    2013-10-01

    Full Text Available Croton species are used in folk medicine in the management of infections, inflammation and oxidative stress-related diseases. In order to isolate, characterize and evaluate the bioactive constituents of Croton menyharthii Pax leaf extracts, repeated column fractionation of the ethyl acetate fraction from a 20% aqueous methanol crude extract afforded three flavonols identified by NMR (1D and 2D spectroscopic methods as myricetrin-3-O-rhamnoside (myricetrin, 1, quercetin-3-O-rhamnoside (2 and quercetin (3 along with an indole alkaloid, (E-N-(4-hydroxycinnamoyl-5-hydroxytryptamine, [trans-N-(p-coumaroyl serotonin, 4]. All the compounds are reported from the leaf extract of this plant for the first time. The crude extracts, four solvent fractions (hexane, DCM, ethyl acetate and butanol and isolated compounds obtained from the leaves were evaluated for their inhibitory effects on selected bacteria, a fungus (Candida albicans, cyclooxygenase (COX-2, α-glucosidase and acetylcholinesterase (AChE. Amongst the compounds, quercetin (3 was the most active against Bacillus subtilis and Candida albicans while myricetrin-3-O-rhamnoside (1 and trans-N-(p-coumaroyl serotonin (4 were the most active compounds against Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus. The inhibitory activity of myricetrin-3-O-rhamnoside (1 against COX-2 was insignificant while that of the other three compounds 2–4 was low. The AChE inhibitory activity of the alkaloid, trans-N-(p-coumaroyl serotonin was high, with a percentage inhibitory activity of 72.6% and an IC50 value of 15.0 µg/mL. The rest of the compounds only had moderate activity. Croton menyharthii leaf extracts and isolated compounds inhibit α-glucosidase at very low IC50 values compared to the synthetic drug acarbose. Structure activity relationship of the isolated flavonols 1–3 is briefly outlined. Compounds 1–4 and the leaf extracts exhibited a broad spectrum of activities. This validates the

  7. Effects of Onion (Allium cepa L. Extract Administration on Intestinal α-Glucosidases Activities and Spikes in Postprandial Blood Glucose Levels in SD Rats Model

    Sun-Ho Kim

    2011-06-01

    Full Text Available Diets high in calories and sweetened foods with disaccharides frequently lead to exaggerated postprandial spikes in blood glucose. This state induces immediate oxidant stress and free radicals which trigger oxidative stress-linked diabetic complications. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes,α-amylase and α-glucosidases, in the digestive organs. Therefore, the inhibitory activity of Korean onion (Allium cepa L. extract against rat intestinal α-glucosidases, such as sucrase, maltase, and porcine pancreatic α-amylase were investigated in vitro and in vivo. The content of quercetin in ethyl alcohol extract of onion skin (EOS was 6.04 g/100 g dried weight of onion skin. The in vitro half-maximal inhibitory concentrations (IC50 of EOS and quercetin, a major phenolic in onion, on rat intestinal sucrase were 0.40 and 0.11 mg/mL, respectively. The postprandial blood glucose lowering effects of EOS and quercetin were compared to a known type 2 diabetes drug (Acarbose, a strong α-glucosidase inhibitor in the Sprague-Dawley (SD rat model. In rats fed on sucrose, EOS significantly reduced the blood glucose spike after sucrose loading. The area under the blood glucose-time curve (AUClast in EOS-treated SD rats (0.5 g-EOS/kg was significantly lower than in untreated SD rats (259.6 ± 5.1 vs. 283.1 ± 19.2 h·mg/dL. The AUClast in quercetin-treated SD rats (0.5 g-quercetin/kg was similar to in EOS-treated group (256.1 ± 3.2 vs. 259.6 ± 5.1 h·mg/dL. Results from this study indicates that although quercetin does have blood glucose lowering potential via α-glucosidase inhibition, there are other bioactive compounds present in onion skin. Furthermore, the effects of two weeks administration of EOS in a high carbohydrate-dietary mixture (Pico 5053 on sucrase and maltase activities in intestine were evaluated in SD rat model

  8. Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator

    Chen YC

    2015-08-01

    Full Text Available Yu-Ching Chen,1 Victor C Kok,1,2 Ching-Hsuan Chien,1 Jorng-Tzong Horng,1,3 Jeffrey J P Tsai11Department of Biomedical Informatics, Asia University, Taichung, 2Department of Internal Medicine, Kuang Tien General Hospital, Taichung, 3Department of Computer Science and Information Engineering, National Central University, Jhongli, TaiwanIntroduction: Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy.Methods: We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325 from the 1998–2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223, sulfonylurea (n=3,965, glitazone (n=53, meglitinide (n=128, acarbose (n=150, and insulin (n=806 groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox’s model was used to estimate multivariable hazard ratios (HRs adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis.Results: The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years. Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11–1.67; P<0.005. No significant differences were observed between other groups. Increased adjusted HRs

  9. Potent α-amylase inhibitory activity of Indian Ayurvedic medicinal plants

    Bhargava Shobha Y

    2011-01-01

    Full Text Available Abstract Background Indian medicinal plants used in the Ayurvedic traditional system to treat diabetes are a valuable source of novel anti-diabetic agents. Pancreatic α-amylase inhibitors offer an effective strategy to lower the levels of post-prandial hyperglycemia via control of starch breakdown. In this study, seventeen Indian medicinal plants with known hypoglycemic properties were subjected to sequential solvent extraction and tested for α-amylase inhibition, in order to assess and evaluate their inhibitory potential on PPA (porcine pancreatic α-amylase. Preliminary phytochemical analysis of the lead extracts was performed in order to determine the probable constituents. Methods Analysis of the 126 extracts, obtained from 17 plants (Aloe vera (L. Burm.f., Adansonia digitata L., Allium sativum L., Casia fistula L., Catharanthus roseus (L. G. Don., Cinnamomum verum Persl., Coccinia grandis (L. Voigt., Linum usitatisumum L., Mangifera indica L., Morus alba L., Nerium oleander L., Ocimum tenuiflorum L., Piper nigrum L., Terminalia chebula Retz., Tinospora cordifolia (Willd. Miers., Trigonella foenum-graceum L., Zingiber officinale Rosc. for PPA inhibition was initially performed qualitatively by starch-iodine colour assay. The lead extracts were further quantified with respect to PPA inhibition using the chromogenic DNSA (3, 5-dinitrosalicylic acid method. Phytochemical constituents of the extracts exhibiting≥ 50% inhibition were analysed qualitatively as well as by GC-MS (Gas chromatography-Mass spectrometry. Results Of the 126 extracts obtained from 17 plants, 17 extracts exhibited PPA inhibitory potential to varying degrees (10%-60.5% while 4 extracts showed low inhibition ( 50% was obtained with 3 isopropanol extracts. All these 3 extracts exhibited concentration dependent inhibition with IC50 values, viz., seeds of Linum usitatisumum (540 μgml-1, leaves of Morus alba (1440 μgml-1 and Ocimum tenuiflorum (8.9 μgml-1. Acarbose as the

  10. Ultrasonic extraction of polysaccharides from Laminaria japonica and their antioxidative and glycosidase inhibitory activities

    Wan, Peng; Yang, Xiaoman; Cai, Bingna; Chen, Hua; Sun, Huili; Chen, Deke; Pan, Jianyu

    2015-08-01

    In the present study, ultrasonic extraction technique (UET) is used to improve the yield of polysaccharides from Laminaria japonica (LJPs). And their antioxidative as well as glycosidase inhibitory activities are investigated. Box-Behnken design (BBD) combined with response surface methodology (RSM) is applied to optimize ultrasonic extraction for polysaccharides. The optimized conditions are obtained as extraction time at 54 min, ultrasonic power at 1050 W, extraction temperature at 80°C and ratio of material to solvent at 1:50 (g mL-1). Under these optimal ultrasonic extraction conditions, an actual experimental yield (5.75% ± 0.3%) is close to the predicted result (5.67%) with no significant difference ( P > 0.05). Vitro antioxidative and glycosidase inhibitory activities tests indicate that the crude polysaccharides (LJP) and two major ethanol precipitated fractions (LJP1 and LJP2) are in a concentration-dependent manner. LJP2 (30%-60% ethanol precipitated polysaccharides) possesses the strongest α-glucosidase inhibitory activity and moderate scavenging activity against hydroxyl radicals (66.09% ± 2.19%, 3.0 mg mL-1). Also, the inhibitory activity against α-glucosidase (59.08% ± 3.79%, 5.0 mg mL-1) is close to that of acarbose (63.99% ± 3.27%, 5.0 mg mL-1). LJP1 (30% ethanol precipitated polysaccharides) exhibits the strongest scavenging activity against hydroxyl radicals (99.80% ± 0.00%, 3.0 mg mL-1) and moderate α-glucosidase inhibitory activity (47.76% ± 1.92%, 5.0 mg mL-1). LJP shows the most remarkable DPPH scavenging activity (66.20% ± 0.11%, 5.0 mg mL-1) but weakest α-glucosidase inhibitory activity (37.77% ± 1.30%, 5.0 mg mL-1). However, all these LJPs exert weak inhibitory effects against α-amylase. These results show that UET is an effective method for extracting bioactive polysaccharides from seaweed materials. LJP1 and LJP2 can be developed as a potential ingredient in hypoglycemic agents or functional food for the management of

  11. 新诊断2型糖尿病患者采取沙格列汀联合二甲双胍治疗的疗效及安全性分析%EFFICACY AND SAFETY OF SHAH GLENN DEAN COMBINED WITH METFORMIN IN THE TREAT- MENT OF THE PATIENTS WITH NEWLY DIAGNOSED TYPE 2 DIABETES

    钱冬

    2015-01-01

    's hos‐pital from February 2012 to January 2014 in type 2 diabetic patients ,using random number table method for grouping ,they were divided into study group and control group ,47 cases in each group .The control group received acarbose and metformin treatment ,the research group were treated by Shah Glenn Dean combined with metformin treatment .Fasting blood glucose (FBG) ,2h postprandial blood glucose (2hPG) , glycosylated hemoglobin (HbA1c) ,fasting insulin ,insulin resistance index (HOMA - IR) ,body weight and body mass index of two groups were recorded before and after treatment ,and medication compliance and adverse reaction rate were compared between the two groups .Results Before treatment ,FBG ,2hPG and HbA1 c values had no significant difference (P>0 .05) between the two groups ,and the fasting insulin level and HOMA -IR value also had no significant difference (P> 0 .05) .After treatment ,FBG ,2hPG and HbA1c in study group were lower than that in the control group ,but the fasting insulin levels were higher and the HOMA -IR value was lower ,the difference was statistically significant (P0 .05);HbA1 c stand‐ard rate was higher in the research group than that in the control group ,the difference was statistically sig‐nificant (P0 .05) .The medication mistakes and wrong of research group wear rate were lower than the control group ,the difference was statistically significant (P< 0 .05) .Conclusion Clinical curative effect of metformin and Shah Glenn Dean therapy in patients with type 2 diabetes is better than metformin and acarbose schemes ,and the security is good ,worthy of further promotion in clinic .

  12. Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control Redução do número de podócitos na fase tardia da nefropatia diabética aloxânica: prevenção pelo controle glicêmico

    Célia Sperandéo Macedo

    2007-10-01

    Full Text Available PURPOSE: To determine podocyte number and GBM thickness in diabetic rats either under glycemic control or without glycemic control at 6 and 12 months after diabetes induction. METHODS: 100 wistar rats weighing 200-300g were divided into 6 groups: Normal group (N6 and N12- 25 rats; Diabetic group (D6 and D12- 25 rats, diabetic treated group ( DT 6 and DT 12- 25 rats on insulin 1,8- 3,0 IU/Kg associated with acarbose (50mg to 100g of food daily mixed in chow. Alloxan was injected intravenously in a dose of 42 mg/Kg of weight. Body weight, waterintake, 24-h diuresis, glycemia and glucosuria were determined before induction, 7 and 14 days after induction and monthly thereafter. Treatment started at day 14. Three groups were sacrificed at 6 months (N6,D6, DT6 and 3 groups at 12 months (N12, D12, DT12 with the renal tissue being prepared for electron microscopy. RESULTS: Glycemia in DT6¨and in DT12 was significantly different from that in D6 and D12 rats and similar to that in N6 and N12 animals. The number of podocytes in DT6 was not different from that in N6 and D6 (median = 11; the number of podocytes in DT12 (median = 11 differed from that in D12 (median = 8, but not from that in N12 (median = 11. GBM thickness in D6 (0.18 micrometers was lower than in D12 (0.29 micrometers; while in DT6 (0.16 micrometers it was lower than in D6 (0.18 micrometers. In DT12 (0.26 micrometers, it was lower than in D12 (0.29 micrometers. CONCLUSION: The control of hyperglycemia prevented GBM thickening in early and late (12 mo alloxan diabetic nephropathy and podocyte number reduction.OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais Diabético (D6,D12 - 25 animais e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada

  13. Pharmacotherapy for hepatic encephalopathy.

    Phongsamran, Paula V; Kim, Jiwon W; Cupo Abbott, Jennifer; Rosenblatt, Angela

    2010-06-18

    associated with neurotoxicity in patients with cirrhosis, including dose-dependent peripheral neuropathy. Vancomycin may be a safer option for HE in patients with chronic liver disease; however, limited experience, possible bacterial overgrowth and risk for enteric bacteria resistance preclude the routine use of vancomycin for HE. Rifaximin is a novel antimicrobial agent with a wide spectrum of activity that has shown promise as an alternative antimicrobial treatment option for HE. Several clinical trials have compared rifaximin to the disaccharides, lactulose and lactitol, and the antimicrobial neomycin. Rifaximin appears to be at least as effective as conventional drug therapy and has been associated with fewer adverse effects due to its limited systemic absorption. The available clinical data appear to support a favourable benefit-risk ratio for rifaximin, which has shown efficacy with an improved tolerability profile. Future studies are needed in order to truly characterize its cost effectiveness in today's healthcare environment. Other less frequently utilized alternative treatment options include administration of benzodiazepine receptor antagonists, branched-chain amino acids, ornithine aspartate, zinc supplementation, sodium benzoate, dopamine receptor agonists, acarbose and probiotics. Presently, there is relatively limited clinical data supporting their routine use in HE. PMID:20518580

  14. 干血滤纸片和白细胞酸性α-葡萄糖苷酶活性测定平台的建立及临床应用%Establishment and clinical application of dried blood spots and mixed leukocytes for determination of acid α-glucosidase activity

    邱文娟; 王霞; 王瑜; 叶军; 韩连书; 张惠文; 顾学范

    2010-01-01

    目的 建立干血滤纸片和门细胞酸性α-葡萄糖苷酶(GAA)活性测定方法 及正常参考值,用于糖原累积病Ⅱ型(GSD Ⅱ)患者的酶学诊断.方法 利用GAA特异性水解荧光底物4-MUG的原理,采用阿卡波糖抑制其同工酶,建立干血滤纸片(DBS)和白细胞测定GAA活性方法 .取700例DBS样本和100例白细胞样本作为正常对照建立DBS和白细胞测定GAA活性正常参考值,并对临床疑诊4例患者及其父母进行GAA活性测定.结果 DBS法具有良好的精密度,室温或低于室温保存至少4周时DBS GAA活性无明显影响.正常新生儿和儿童-成人DBS的GAA参考范围分别为8.92~60.03 pmol/(punch·h)和8.00~37.43 pmol/(punch·h);正常人白细胞GAA参考范围:12.56~50.26 nmol/(mg蛋白·h),共检出4例GSD Ⅱ型患者.结论 DBS法测定GAA活性具有敏感、快速、高通量等特点,适于GSD Ⅱ型高危人群筛查和诊断;白细胞法测定GAA活性也具有快速、特异性高等特点,适于患者的确诊.%Objective Glycogen storage disease type Ⅱ(GSD Ⅱ,Pompe disease)is caused by the deficiency of acid α-glucosidase(GAA)that leads to lysosomal glycogen accumulation.Early diagnosis and treatment of GSD Ⅱ are considered to be critical for maximum efficacy of the enzyme replacement therapy.The aim of this study was to introduce two reliable methods and to generate the reference range of GAA activitv.Method The assay of GAA activity was performed in dried blood spots(DBS)and mixed leukocytes with acarbose to eliminate isoenzyme interference and to generate the reference range.GAA activitv was assayed in 700 specimens for DBS from normal subjects and 100 specimens for mixed leukocytes from normal subjects to set up reference range.GAA activity in the samples of 4 patients who were clinically suspected of GSD Ⅱ and their parents were also assayed.Result The intra-run and inter-run precision of the DBS method wag less than 10%.GAA activity tested by DBS was

  15. 我院2006-2010年抗糖尿病药物应用分析%Utilization analysis of anti-diabetic drugs in our hospital during 2006-2010

    刘朋; 纪立伟; 梁晓丽

    2013-01-01

      目的:分析北京医院抗糖尿病药的应用情况,为临床合理用药提供参考。方法:对卫生部北京医院2006–2010年抗糖尿病药物的种类、用量、销售金额、用药频度、日均费用等进行分析。结果:我院口服抗糖尿病药的销售金额占抗糖尿病药总金额的70%,其中,以α-葡萄糖苷酶抑制剂所占比例最高,胰岛素类约占30%;阿卡波糖、二甲双胍、诺和灵30R的DDDs较高,临床较为常用;二甲双胍、格列美脲、格列喹酮的DDC较低;噻唑烷二酮类药物的销售金额和DDDs逐年下降,其他药品的销售金额和DDDs均呈上升趋势,DDC逐年下降。瑞格列奈、那格列奈、甘精胰岛素的排序比值较低。结论:我院2006–2010年抗糖尿病药物的使用品种相对稳定,基本满足临床安全、经济、有效用药的需求。%Objective:To analyze the application situation of antidiabetic drugs in our hospital to provide reference for clinical rational drug use. Methods:The variety, amount, consumption sum, DDDs and average daily cost of antidiabetic drugs used in our hospital during 2006–2010 were analyzed retrospectively. Results:Sales amount of oral antidiabetic drugs accounted for 70%of the total amount of antidiabetic drugs. The sales amount ofα-glucosidase inhibitor was the largest and the sales amount of insulin accounted for about 30%of the total amount of antidiabetic drugs. The values of DDDs of acarbose, metformin and Novolin 30R were higher than that of other antidiabetic drugs due to more common use in clinic. The values of DDC of metformin, glimepiride, gliquidone were lower. Exception for the decrease in the sales amount and DDDs of thiazolidinediones, the sales amount and DDDs of other antidiabetic drugs showed an upward trend. The ratios of consumption sum sequence to DDDs sequence of repaglinide, nateglinide and the insulin glargine were smaller. Conclusion:The oral antidiabetic drugs used in our

  16. [A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].

    Ozawa, Hikaru; Murai, Yuriko; Ozawa, Terutaka

    2003-01-01

    recombinant products prevailed throughout the 1990s. Human insulin analogues (i.e., Insulin lispro and Insulin aspart) appeared in 2001. These are applied for after-meal glycosmia owing to their ultrarapid onset of activity. Self-injection by DM patients was legalized in 1981. To make the infection technique sure and easy, cartridge (pen-type) and disposable kit-type needles were devised in the 1990s. 2) Oral hypoglycemic drugs: Instead of the exclusive parenteral usage of insulins, there was also demand for oral dosage forms. The first of the sulfonyrlurea (SU) group, BZ-55, was used for DM clinically in 1955 in Germany. But it was soon withdrawn because of its antibacterial action. This led to the development of various SU groups. Tolbutamide (1956), chlorpropamide (1959), acetohexamide (1964) and tolazamide (1961) were introduced to Japan as first-generation SUs. Then glyclopyramide (Kyorin, 1965), glybenclamide (1971), gliclazide (1984) and glimepiride (1999) appeared as the second-generation SUs. These were used orally for Type 2 diabetes. Biguanide (BG) group, phenformin HC1 (1959), metformin HC1 (1961) and buformin HC1 (1961) had also been in use by oral treatment of Type 2 diabetes. SU appears to act by increasing the sensitivity of b-cells, which secrete insulin. BG probably exerts by increasing glucose transport across the membranes of target organs. 3) New types of antidiabetic drugs: a-Glucosidase inhibitors (i.e., acarbose: Bayer, 1993; and voglibose: Takeda, 1994) act on hyperglycemia after meals by decreasing glucose absorption. Thiazolidinedione compounds, such as troglitazone (Sankyo, 1995) and pioglitazone HC1 (Takeda, 1994) act by increasing the insulin sensitivity of the target tissues. These are useful for Type 2 DM patients when SUs are ineffective. Nevertheless, troglitazone was discontinued in 2000 due to severe liver damage. Nateglinide (Ajinomoto Co., 1999), which is a D-phenylalanine derivative acting similar to SUs, is useful orally for after

  17. Study on the Optimum Proportion of Radix Astragalus with Flos Carthami on alpha - Glucosidase and Antioxidant Activities%黄芪与红花抑制α-葡萄糖苷酶及抗氧化活性的最佳配比研究

    廖晖; 王孝敏

    2015-01-01

    oligomer to deter-mine the impacts of the samples to yeast alpha glycosidase enzyme activity,in which,acarbose was taken as the positive control. Oxygen radial absorbance capacity(ORAC)was adopted to determine the antioxidant ac-tivity of samples,in which,vitamin C was taken as the positive control. Results The astragaloside 0. 127 mg contained in each 1 ml radix astragalus extraction and the general flavone 0. 57 mg in each 1 ml flos carthami extraction. All of them met the content requirement of CFDA - relevant activity component. IC50 of the inhibi-tion of flos carthami for alpha - glucosidase activity was(32. 8 ± 5. 7)μg/ ml,significantly lower than that of radix astragalus[(1686 ± 810)μg/ ml,P < 0. 01]. IC50 was lower significantly at the ratios of radix astragalus and flos carthami as 10: 1,5: 1 and 2: 1 as compared with that at the ratio of 20: 1(P <0. 01)separately. ORAC value of flos carthami was(1090 ± 161)μmol TE/ g,higher significantly than that of radix astragalus[(205 ± 32)μmol TE/ g,P <0. 01]. When the ratios of the crude herbal materials were 5: 1 and 2: 1,ORAC value was higher significantly than that at 20: 1 and 10: 1 respectively(P <0. 01). Conclusion Both radix astragalus and flos carthami act on the inhibition of yeast alpha - glucosidase activity and has a certain of antioxidant activity. While improving the above indexes,the actions of the crude herbal materials are significant at the ratio of 5:1 and 2: 1 as compared with those at 20: 1(P < 0. 01).

  18. The effects of walking exercise on glycometabolism, dynamic blood pressure and the quality of life of patients with hypertension and type 2 diabetes%步行运动对高血压合并糖尿病患者糖代谢、动态血压及生活质量的影响

    王正斌; 邱春光; 黄振文; 韩战营; 孙国举; 孙寒

    2014-01-01

    Objective To explore the effects of walking exercise on glycometabolism,dynamic blood pressure and the quality of life of patients with both hypertension and type 2 diabetes on the basis of conventional drug treatment.Methods Sixty-two patients with both hypertension and diabetes who could support taking walking exercise of more than 5,000 steps/d were randomly divided into a walking exercise group (32 cases) and a control group (30 cases).Both groups were given conventional drug treatment (including valsartan,acarbose and metformin).Those in the walking exercise group took more than 10,000 steps/d of aerobic exercise while the patients in the control group were just given normal community care.This continued for a period of 3 months.Fasting plasma glucose (FPG),glycated hemoglobin-A1C (HbA1c),fasting insulin (FINS),the homeostasis model of assessment for insulin resistence index (HOMA-IR),the homeostasis model of assessment for insulin sensitivity (HOMA-IS),dynamic blood pressure parameters and quality of life were observed.Results In the walking exercise group,the FPG,HbA1c,FINS,HOMA-IR,HOMA-IS,dynamic blood pressure and quality of life indicators were all significantly different after 3 months of daily walking exercise compared with either baseline or the control group.Conclusion Accompanied by conventional drug therapy,10,000 steps/d of walking exercise can improve the glucose metabolism,dynamic blood pressure and quality of life of patients suffering from mild hypertension and type 2 diabetes.%目的 观察在常规药物治疗基础上辅以步行运动对高血压合并2型糖尿病患者糖代谢、动态血压及生活质量的影响.方法 应用计步器筛选出62例在我科门诊或住院治疗且步行运动量<5000步/d的高血压合并2型糖尿病患者,采用随机数字表法将其分为运动组(32例)及对照组(30例).2组患者均给予常规药物(包括缬沙坦、二甲双胍、阿卡波糖)治疗,运动组患

  19. 甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响%The effect of insulin glargine combined with carbose on blood glucose attaining standardand pancreatic β cell function of type 2 diabetic patients

    包灵敏; 刘存安

    2013-01-01

    Objective To explore the effect of insulin glargine combined with carbose onblood glucose attaining standard and pancreatic β cell function of type 2 diabetic patients.Methods 70 type 2 diabetic patients were divided into observation group and control group.All the patients got fundamental treatment as diet control and physical exercise.Patients of observing group got extra treatment as using insulin glargine combined with carbose,while patients of control group got extra treatment as using premixed insulin 30R(isophane protamine biosynthetic human insulin),all the treatment lasted for 8 weeks.Results 8 weeks after treatment,the rate of reaching standard of FBG and 2h postprandial plasma glucose and glycosylated hemoglobin (95.0%,85.0% and 77.5%) of observing group were significantly higher than those of control group (77.5%,62.5% and 55.0%) (x2 =5.16,5.23 and 4.53,all P <0.05).The levels of FCP and PCP increased significantly in both groups than that of before treatment (t =2.43,2.32,2.28,2.19,all P < 0.05),and the change of observation group was more obviously than that of control group (t =2.17,2.13,all P < 0.05).The occurrence rate of hypoglycemia of observation group was significantly lower than that of control group(x2 =4.11,P <0.05).Conclusion Treating diabetic patient by insulin glargine combined with acarbose has high safety,and helps to reach the standard of FBG and glycosylated hemoglobin,reduce the incurrence rate of hypoglycemia,protect and improve the function of pancreatic 3 cell,and postpone the beginning and progress of complication.%目的 探讨甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响.方法 选择2型糖尿病患者70例,按就诊病历号顺序随机分为观察组与对照组.两组患者均予以饮食控制和体育锻炼等基础治疗.观察组在此基础上予以甘精胰岛素联合阿卡波糖治疗,对照组在此基础上予以精蛋白生物合成人