Inhibition Of Carbohydrate Hydrolyzing Enzymes Research Articles

The potential of chalcone-capped gold nanoparticles for the management of diabetes mellitus

Searching for new natural bioactive capping agents represent an urgent priority in the green synthesis of metal nanoparticles. Additionaly, the biosaftey of metal nanparticles is a major concern especially in medical applications. Recently, the use of pharmacollogicaly active natural products as capping agents has been deployed to avoid toxic effects during the nanoparticles preparation and to enhance their drugability compared with convential drugs. Helichrysum foetidum is a South African medicinal plant used in folk medicine for the treatment of different human pathologies, and it is known to contain a variety of bioactive compounds. Herein, the total extract and two pure chalcones, helichrysetin and helichrysin, isolated from the same plant were successfully used to synthesize quasi-monodispersed gold nanoparticles in the size range of 2–12 nm. The bio-evaluation of samples indicated that the AuNP/capping agent conjugates are biostable, and have different biological profiles from the total extract/pure compounds. The enzymatic inhibition assays showed significant inhibition by the total extract, helichrysetin and their gold nanoparticles. Interestingly, a similar activity was observed for glucose uptake in HEK293 treated cells. On the other hand, all the tested samples relatively demonstrated no cytotoxicity when tested against the HaCaT keratinocytes. In conclusion, the study demonstrated potential enhancement of glucose uptake in mammalian kidney cells, and inhibition of carbohydrate-hydrolysing enzymes by green synthesized gold nanoparticles of H. foetidum. It also provides a therapeutic appraisal of AuNPs/chalcones conjugate towards the development of antidiabetes drugs derived from H. foetidum and its gold nanoparticles.

Possible anti-diabetic potentials of Annona muricata (soursop): inhibition of \u03b1-amylase and \u03b1-glucosidase activities

BackgroundAnnona muricata has been used in folklore in the management of diabetes. A major strategy in decreasing postprandial hyperglycemia in diabetes involves the inhibition of carbohydrate-hydrolyzing enzymes - α-amylase and α-glucosidase. Thus, this study evaluated the in vivo and in vitro inhibitory potentials of the different parts (fruit-pulp, leaf, stem-bark and root-bark) of Annona muricata.MethodsA total of 120 Wistar rats were treated with methanol extracts for 28 days after which blood and tissue samples were collected for α-amylase assay. In vitro inhibitory properties of methanol, ethyl acetate and dichloromethane extracts of the various parts of the plant on α-amylase and α-glucosidase activities were performed using standard procedures. The mode and mechanism of interactions between the enzymes and extracts (and isolated acetogenin) were determined using various kinetic interpolations and in silico experiments.ResultThe fruit-pulp and root-bark methanolic extracts better -inhibited plasma and tissue amylase in vivo. The in vitro studies revealed that the stem-bark methanolic, fruit-pulp ethyl acetate, and leaf dichloromethane extracts, better inhibited α-amylase activity compared with the standard acarbose. Also, the leaf methanol, fruit-pulp ethyl acetate, and root-bark dichloromethane extract better inhibited α-glucosidase activity. These observations were corroborated with their higher Bmax and Vmax and lower Kd values. All the extracts exhibited an “uncompetitive” type of inhibition pattern. Also, the isolated acetogenin (15-acetyl guanacone) from the fruit-pulp showed a better binding affinity compared to the standard drug, Metformin.ConclusionBetter natural remedy for diabetics can be obtained from Annona muricata with minimal or no adverse side effects.

Molecular Insight and Mode of Inhibition of α-Glucosidase and α-Amylase by Pahangensin A from Alpinia pahangensis Ridl.

The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC50 =114.80 μm) and α-glucosidase (IC50 =153.87 μm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.

Portulaca oleracea L. (Purslane) extracts display antioxidant and hypoglycaemic effects

Purslane (Portulaca oleracea L.) is a member of the family Portulacaceae. Due to its many health benefits, it is listed in a World Health Organization database. The aim of this work is to investigate the purslane extracts for their chemical profile and bioactivity.In this study, two different solvents (MeOH/H2O and EtOH) were applied to fresh and dried leaves. The extracts were analysed using HPLC-DAD. Phenolic acids (caffeic acid, p-coumaric acid and ferulic acid) and flavonoids (apigenin, kaempferol, luteolin, quercetin, isorhamnetin, kaempferol-3-O-glucoside and rutin) were identified in all samples. Quercetin and p-coumaric acid were the most abundant compounds. Total antioxidant activity was measured by using the ABTS and DPPH tests, and the ferric reducing antioxidant power (FRAP) assay. Hypoglycaemic properties were investigated via the inhibition of carbohydrate-hydrolysing enzymes, α-amylase and α-glucosidase.Fresh hydroalcoholic purslane extract exhibited the highest radical scavenging potential in both ABTS and DPPH test (IC50 values of 52.86 and 66.98 μg/mL, respectively), whereas dried hydroalcoholic purslane extract showed the highest α-glucosidase inhibitory potential (IC50 value of 45.05 μg/mL). Collectively these data show the health properties of this widely consumed salad plant.

Enhanced Glucose Uptake in Human Liver Cells and Inhibition of Carbohydrate Hydrolyzing Enzymes by Nordic Berry Extracts

A Western lifestyle with low physical activity and a diet rich in sugar, fat and processed food contribute to higher incidences of diabetes and obesity. Enhanced glucose uptake in human liver cells was observed after treatment with phenolic extracts from different Nordic berries. All berry extracts showed higher inhibition against α-amylase and α-glucosidase than the anti-diabetic agent acarbose. Total phenolic content and phenolic profiles in addition to antioxidant activities, were also investigated. The berries were extracted with 80% methanol on an accelerated solvent extraction system (ASE) and then purified by C-18 solid phase extraction (SPE). Among the ASE methanol extracts, black chokeberry, crowberry and elderberry extracts showed high stimulation of glucose uptake in HepG2 cells and also considerable inhibitory effect towards carbohydrate hydrolyzing enzymes. SPE extracts with higher concentrations of phenolics, resulted in increased glucose uptake and enhanced inhibition of α-amylase and α-glucosidase compared to the ASE extracts. Crowberry and cloudberry were the most potent 15-lipoxygenase inhibitors, while bog whortleberry and lingonberry were the most active xanthine oxidase inhibitors. These results increase the value of these berries as a component of a healthy Nordic diet and have a potential benefit against diabetes.

Phenolic Elderberry Extracts, Anthocyanins, Procyanidins, and Metabolites Influence Glucose and Fatty Acid Uptake in Human Skeletal Muscle Cells.

Uptake of glucose and fatty acids in skeletal muscle is of interest for type 2 diabetes treatment. The aim was to study glucose and fatty acid uptake in skeletal muscle cells, antioxidant effects, and inhibition of carbohydrate-hydrolyzing enzymes by elderberries. Enhanced glucose and oleic acid uptake in human skeletal muscle cells were observed after treatment with phenolic elderberry extracts, anthocyanins, procyanidins, and their metabolites. The 96% EtOH and the acidified MeOH extracts were highly active. Of the isolated substances, cyanidin-3-glucoside and cyanidin-3-sambubioside showed highest stimulation of uptake. Phloroglucinol aldehyde was most active among the metabolites. Isolated anthocyanins and procyanidins are strong radical scavengers and are good inhibitors of 15-lipoxygenase and moderate inhibitors of xanthine oxidase. As α-amylase and α-glucosidase inhibitors, they are considerably better than the positive control acarbose. The antidiabetic property of elderberry phenolics increases the nutritional value of this plant and indicates potential as functional food against diabetes.

Poncirus trifoliata (L.) Raf.: Chemical composition, antioxidant properties and hypoglycaemic activity via the inhibition of α-amylase and α-glucosidase enzymes

The aim of this study was to investigate the phytochemical content of Poncirus trifoliata (L.) Raf. (Rutaceae) and to assess its hypoglycaemic and antioxidant effects. Hesperidin, naringin and chlorogenic acid were the most abundant compounds of the juice. Peel essential oil showed that limonene, myrcene, p-cimene and β-pinene were its main components. The antioxidant activity was studied through different in vitro tests. The hypoglycaemic effects were analysed via inhibition of carbohydrate-hydrolysing enzymes. IC50 values in the range 30.38–39.25 µg/mL were found respectively for juice and peel oil in the DPPH test. Juice inhibited α-amylase and α-glucosidase with IC50 values respectively of 138.14 and 81.27 µg/mL. Polyphenolic compounds identified in the juice were investigated. While neoeriocitrin displayed the strongest antioxidant activity and inhibited α-amylase (IC50 of 4.69 vs 77.45 µM for acarbose), didymin was found to be the most bioactive flavonoid against alpha-glucosidase (IC50 of 4.20 vs 54.99 µM for acarbose).

The α-Glucosidase and α-Amylase Enzyme Inhibitory of Hydroxytyrosol and Oleuropein.

To date, numerous studies have reported on the antidiabetic properties of various plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The objective of this research was to evaluate the inhibitory effect of the hydroxytyrosol and the oleuropein against α-amylase and α-glucosidase. The hydroxytyrosol was purified from olive leaves. The result shows that the hydroxytyrosol had the strongest α-glucosidase inhibitory effect with IC50 values of 150 μM with mild inhibition against α-amylase. The enzyme kinetic studies, using Lineweaver-Burk indicated that, in the presence of the hydroxytyrosol, the Michaelis-Menton constant (Km) remained constant but the maximal velocity (Vmax) decreased, revealing a non-competitive type of inhibition with inhibition constants; Ki for the formation of the inhibitor-enzyme complex and Kis for the formation of the inhibitor-enzyme-substrate complex of 104.3 and 150.1 μM, respectively. On the other hand, oleuropein showedan uncompetitive inhibition. The concentrations used in this work were below cytotoxic levels observed at 400 μM. However, at 600 μM, the hydroxytyrosol significantly decreased viability of the Caco-2 cells (p < 0.05) and in the case of the oleuropein, there's an increase in cell number compared to control (p < 0.05). These results suggest that the hydroxytyrosol and oleuropein are two potential effective α-glucosidase inhibitors for management of postprandial hyperglycemia.

The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts

To date, numerous studies have reported on the antidiabetic properties of various plant extracts through inhibition of carbohydrate-hydrolysing enzymes. The objective of this research was to evaluate extracts of seaweeds for α-amylase and α-glucosidase inhibitory effects. Cold water and ethanol extracts of 15 seaweeds were initially screened and from this, five brown seaweed species were chosen. The cold water and ethanol extracts of Ascophyllum nodosum had the strongest α-amylase inhibitory effect with IC50 values of 53.6 and 44.7μg/ml, respectively. Moreover, the extracts of Fucus vesiculosus Linnaeus were found to be potent inhibitors of α-glucosidase with IC50 values of 0.32 and 0.49μg/ml. The observed effects were associated with the phenolic content and antioxidant activity of the extracts, and the concentrations used were below cytotoxic levels. Overall, our findings suggest that brown seaweed extracts may limit the release of simple sugars from the gut and thereby alleviate postprandial hyperglycaemia.

Correlation between enzymes inhibitory effects and antioxidant activities of standardized fractions of methanolic extract obtained from Ficus deltoidea leaves

Recently, there has been increasing interest in Ficus deltoidea (Moracea) due to its chemical composition and the potential health benefits. The leaves of the plant have been suggested to have potential antidiabetic effects. Inhibition of carbohydrate-hydrolysing enzymes, such as α-glucosidase and α-amylase is one of the therapeutic approaches to control postprandial hyperglycemia. In this study, enzymes inhibitory effect and antioxidant properties of different fractions of methanolic extract obtained from F. deltoidea leaves was evaluated. Further, the possible relationship between pharmacological properties and phytochemical content of fractions was investigated. The n-butanol fraction showed significant α-glucosidase and α-amylase inhibitory effects (IC 50 values 15.1 and 39.42 μg/ml, respectively) along with the remarkable antioxidant activity when compared to the other fractions. High performance liquid chromatography (HPLC) chemical profiling of the n-butanol fraction revealed that the contents of isovitexin (24.63 mg/g) and vitexin (8.3 mg/g) were found to be significantly higher than the other fractions. These results indicate that F. deltoidea could be the potential source of promising anti-diabetic drug. Key words : Ficus deltoidea, enzymes, phytochemical, high performance liquid chromatography (HPLC), isovitexin, vitexin.

GLYCOSIDASE INHIBITORY ACTIVITY AND ANTIOXIDANT PROPERTIES OF A POLYSACCHARIDE FROM THE MUSHROOM INONOTUS OBLIQUUS

ABSTRACT A water-soluble polysaccharide from Inonotus obliquus (IOPS) was isolated from the mushroom Inonotus obliquus (Fr.) Pilat. The chemical compositions, molecular weight and inhibitory activities on glycosidase and antioxidant properties of IOPS were investigated. The results indicated that IOPS was an acid protein-bound polysaccharide, with a molecular weight of 1.7 × 104 Da and the contents of neutral sugar, protein and uronic acids being 42.5, 18.5 and 6.1%, respectively. IOPS exhibited an inhibitory activity against α-glucosidase with the IC50 value of 93.3 µg/mL, whereas it had no effective inhibition on α-amylase. Results of antioxidant activity assays revealed that IOPS had inhibitory activity on the concentration-dependent quenching of 1,1-Diphenyl-2-picrylhydrazyl and hydroxyl radicals. Furthermore, IOPS inhibited the formation of thiobarbituric acid-reactive substances in Fe2+/ascorbate-induced lipid peroxidation in rat liver tissue. These results clearly demonstrated that IOPS was one of the main bioactive components of I. obliquus that contributed to hypoglycemic activity and antioxidant activity. PRACTICAL APPLICATIONS Diabetes mellitus is one of the primary threats to human health because of its increasing prevalence, chronic course and disabling complications. Postprandial hyperglycemia plays an important role in the development of type 2 diabetes mellitus and complications associated with the disease. One therapeutic approach to decrease postprandial hyperglycemia is to retard the absorption of glucose through inhibition of carbohydrate-hydrolyzing enzymes in the digestive organs. In this study, a polysaccharide isolated from the mushroom Inonotus obliquus (IOPS) was shown to have notable glycosidase inhibitory effects and antioxidant activities. This research will benefit for the investigation of effective and safe α-glucosidase inhibitors from natural materials. IOPS could be a good candidate for application in food and medicinal fields. It might be developed for functional food or lead compounds for use in antidiabetes.