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Molecules (Basel, Switzerland) Apr 2024This study synthesized a novel oat -glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and...
This study synthesized a novel oat -glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 10 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.
Topics: Humans; Chromium; Hypoglycemic Agents; beta-Glucans; Hep G2 Cells; alpha-Glucosidases; alpha-Amylases; Insulin Resistance; Glucose; Signal Transduction; Glucose Transporter Type 4; Avena; Glycoside Hydrolase Inhibitors; Coordination Complexes
PubMed: 38731488
DOI: 10.3390/molecules29091998 -
Bioorganic Chemistry Jun 2024Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy),...
Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 µM; α-Glu: 248.3 µM) with IC value of 6.2-23.6 µM toward α-Amy and 39.8-124.6 µM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs.
Topics: alpha-Amylases; alpha-Glucosidases; Glycoside Hydrolase Inhibitors; Lignans; Structure-Activity Relationship; Humans; Molecular Structure; Dose-Response Relationship, Drug; Molecular Docking Simulation; Hypoglycemic Agents; Enzyme Inhibitors
PubMed: 38723423
DOI: 10.1016/j.bioorg.2024.107392 -
Molecules (Basel, Switzerland) Apr 2024We prepared network polysaccharide nanoscopic hydrogels by crosslinking water-soluble chitosan (WSCS) with a carboxylate-terminated maltooligosaccharide crosslinker via...
We prepared network polysaccharide nanoscopic hydrogels by crosslinking water-soluble chitosan (WSCS) with a carboxylate-terminated maltooligosaccharide crosslinker via condensation. In this study, the enzymatic elongation of amylose chains on chitosan-based network polysaccharides by glucan phosphorylase (GP) catalysis was performed to obtain assembly materials. Maltoheptaose (Glc) primers for GP-catalyzed enzymatic polymerization were first introduced into WSCS by reductive amination. Crosslinking of the product with the above-mentioned crosslinker by condensation was then performed to produce Glc-modified network polysaccharides. The GP-catalyzed enzymatic polymerization of the α-d-glucose 1-phosphate monomer from the Glc primers on the network polysaccharides was conducted, where the elongated amylose chains formed double helices. Enzymatic disintegration of the resulting network polysaccharide assembly successfully occurred by α-amylase-catalyzed hydrolysis of the double helical amyloses. The encapsulation and release of a fluorescent dye, Rhodamine B, using the CS-based network polysaccharides were also achieved by means of the above two enzymatic approaches.
Topics: Chitosan; Fluorescent Dyes; Polysaccharides; Rhodamines; Hydrogels; alpha-Amylases; Hydrolysis; Amylose; Polymerization; Oligosaccharides; Glucosephosphates; Glucans
PubMed: 38675624
DOI: 10.3390/molecules29081804 -
Scientific Reports Apr 2024Copper-doped ZnO nanoparticles with the formula ZnO, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and...
Copper-doped ZnO nanoparticles with the formula ZnO, where x = 0.0, 0.03, 0.05, and 0.07 were produced using the co-precipitation process. Physical, chemical, and structural properties were properly examined. Powdered X-ray diffraction (P-XRD) patterns revealed the formation of hexagonal wurtzite crystal structure in all samples, through atomic substitutional incorporation in the Cu-doped ZnO lattice. The presence of Cu ions and their dissolution in the host ZnO crystal structure was supported by FT-IR spectra. HR-TEM images were used to assess the average size, morphology, and shape regularity of the synthesized samples. The form and homogeneity of the ZnO changed when Cu ions were substituted, as evidenced by FE-SEM/EDX analysis. The presence of copper signals in the Cu-doped samples indicates that the doping was successful. The decrease in zeta potential with an increased copper doping percentage designates that the nanoparticles (NPs) are more stable, which could be attributed to an increase in the ionic strength of the aqueous solution. The synthesized NPs were evaluated for their substantial in vitro antioxidant properties. In addition, the antimicrobial efficacy of the materials was tested against pathogenic microorganisms. Regarding the anti-diabetic activity, the 7Cu ZnO sample showed the highest inhibitory effect on the α-amylase enzyme. No variations were observed in the activities of the acetylcholinesterase enzyme (AChE) and proteinase enzymes with ZnO and samples doped with different concentrations of Cu. Therefore, further studies are recommended to reveal the in-vitro anti-diabetic activity of the studied doped samples. Finally, molecular docking provided valuable insights into the potential binding interactions of Cu-doped ZnO with α-amylase, FabH of E. coli, and Penicillin-binding proteins of S. aureus. These outcomes suggest that the prepared materials may have an inhibitory effect on enzymes and hold promise in the battle against microbial infections and diabetes.
Topics: Zinc Oxide; Molecular Docking Simulation; Spectroscopy, Fourier Transform Infrared; Copper; Escherichia coli; Staphylococcus aureus; Acetylcholinesterase; Ions; alpha-Amylases
PubMed: 38641640
DOI: 10.1038/s41598-024-59088-2 -
International Journal of Molecular... Mar 2024Erythritol has shown excellent insecticidal performance against a wide range of insect species, but the molecular mechanism by which it causes insect mortality and...
Erythritol has shown excellent insecticidal performance against a wide range of insect species, but the molecular mechanism by which it causes insect mortality and sterility is not fully understood. The mortality and sterility of were assessed after feeding with 1M erythritol for 72 h and 96 h, and gene expression profiles were further compared through RNA sequencing. Enrichment analysis of GO and KEGG revealed that expressions of the adipokinetic hormone gene (), amylase gene (), α-glucosidase gene (, , ), and triglyceride lipase gene () were significantly up-regulated, while insulin-like peptide genes (, and ) were dramatically down-regulated. Seventeen genes associated with eggshell assembly, including (down 315-fold), (down 2014-fold) and (down 6034-fold), were significantly down-regulated or even showed no expression. However, there were no significant differences in the expression of three diuretic hormone genes (, , ) and eight aquaporin genes (, , , , , , and ) involved in osmolality regulation (all value > 0.05). We concluded that erythritol, a competitive inhibitor of α-glucosidase, severely reduced substrates and enzyme binding, inhibiting effective carbohydrate hydrolysis in the midgut and eventually causing death due to energy deprivation. It was clear that did not die from the osmolality of the hemolymph. Our findings elucidate the molecular mechanism underlying the mortality and sterility in induced by erythritol feeding. It also provides an important theoretical basis for the application of erythritol as an environmentally friendly pesticide.
Topics: Animals; Female; Transcriptome; Drosophila melanogaster; Oviposition; alpha-Glucosidases; Gene Expression Profiling; Erythritol; Infertility; Amylases; Drosophila Proteins
PubMed: 38612549
DOI: 10.3390/ijms25073738 -
Molecules (Basel, Switzerland) Mar 2024In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan...
In this study, the α-glucosidase (maltase-glucoamylase: MGAM) and α-amylase inhibitory properties elicited by xylooligosaccharides (XOSs) prepared from dulse xylan were analysed as a potential mechanism to control postprandial hyperglycaemia for type-2 diabetes prevention and treatment. Xylan was purified from red alga dulse powder and used for enzymatic hydrolysis using Sucrase X to produce XOSs. Fractionation of XOSs produced xylobiose (X2), β-(1→3)-xylosyl xylobiose (DX3), xylotriose (X3), β-(1→3)-xylosyl-xylotriose (DX4), and a dulse XOS mixture with ≥ 4 xylose units (DXM). The different fractions exhibited moderate MGAM (IC = 11.41-23.44 mg/mL) and α-amylase (IC = 18.07-53.04 mg/mL) inhibitory activity, which was lower than that of acarbose. Kinetics studies revealed that XOSs bound to the active site of carbohydrate digestive enzymes, limiting access to the substrate by competitive inhibition. A molecular docking analysis of XOSs with MGAM and α-amylase clearly showed moderate strength of interactions, both hydrogen bonds and non-bonded contacts, at the active site of the enzymes. Overall, XOSs from dulse could prevent postprandial hyperglycaemia as functional food by a usual and continuous consumption.
Topics: Humans; alpha-Amylases; alpha-Glucosidases; Hypoglycemic Agents; Xylans; Molecular Docking Simulation; Oligosaccharides; Hyperglycemia; Edible Seaweeds; Rhodophyta; Glucuronates
PubMed: 38611816
DOI: 10.3390/molecules29071536 -
Molecules (Basel, Switzerland) Mar 2024The purpose of this study was to determine the content of certain phenolic compounds, antioxidant activity, pressing efficiency, extract content, and sugars in celeriac...
The purpose of this study was to determine the content of certain phenolic compounds, antioxidant activity, pressing efficiency, extract content, and sugars in celeriac juices obtained from the pulp after α-amylase treatment from . The test material consisted of peeled and unpeeled celery pulp kept at a temperature of 25 °C with and without the enzyme for a period of 30 and 60 min. The juices obtained from them were analyzed for the content of selected phenolic acids and flavonoids using the UPLC-PDA-ESI-MS/MS method, for antioxidant activity measured using the ABTS˙ and DPPH˙ method, and for the total polyphenol content using the F-C method. Additionally, the juice pressing efficiency, the extract content using the refractometer method, and the sugar content using the HPLC method were checked. Significantly higher antioxidant activity, pressing yield, and average content of caffeic acid glucoside, quinic acid, kaempferol-3,7-di--glucoside, and chrysoeriol-7--apiosylglucoside were obtained in juices from peeled celery. Maceration of the pulp with amylase resulted in a significant reduction in antioxidant activity compared to control samples. An is-total increase of 17-41% in total flavonoid content was observed in all juices tested after treatment with the enzyme for 30 and 60 min, and the phenolic acid content increased by 4-41% after treatment of the pulp with amylase for 60 min. The 60 min holding of the pulp at 25 °C, including with the enzyme, was shown to decrease the antioxidant activity and the content of quinic acid, ferulic acid, and chrysoriol-7--apiose-glucoside in the juices tested compared to the samples held for 30 min, while the content of other phenolic acids and flavonoids increased. In addition, after 60 min of enzymatic maceration, the pressing yield of the juices increased.
Topics: Apium; alpha-Amylases; Aspergillus oryzae; Antioxidants; Quinic Acid; Tandem Mass Spectrometry; Vegetables; Phenols; Amylases; Flavonoids; Glucosides; Plant Extracts; Hydroxybenzoates
PubMed: 38611718
DOI: 10.3390/molecules29071438 -
Study of the changes on the physicochemical properties of isolated lentil starch during germination.International Journal of Biological... May 2024In this work, the changes in the composition of the flours and in the morphological, structural, thermal, vibrational, rheological, and functional properties of the...
In this work, the changes in the composition of the flours and in the morphological, structural, thermal, vibrational, rheological, and functional properties of the isolated lentil starch during the germination process were investigated. The fiber, fat, and ash content of the flours decreased and the protein content increased, while the apparent amylose content of the starch granules remained constant. Using scanning electron microscopy (SEM), the starch granules remained intact during germination, and no enzymatic activity of α- and β-amylases was observed. X-ray diffraction shows that the starch has nanocrystals with hexagonal structure which predominate over the nanocrystals with orthorhombic structure and are classified as C-type starch. The most important result is that these nanocrystals do not play an important role during germination. As the germination time progresses, differential scanning calorimetry (DSC) shows a decrease in the gelatinization temperature (T) of the starch, ranging from 70.34 ± 0.25 °C for the native lentil starch to values of 67.16 ± 0.37 °C for the starch on the fourth day of germination (ILS4), this transition being related to the solvation of the nanocrystals. On the other hand, the pasting profiles show no significant changes during germination, indicating that no significant changes in starch content occur during germination. Starch degradation is essential for the production of malt for fermented beverages. This fact makes sprouted lentils not a candidate for the short-term fermentation required in the beverage industry.
Topics: Lens Plant; Germination; Starch; Chemical Phenomena; Amylose; Temperature; Rheology
PubMed: 38599432
DOI: 10.1016/j.ijbiomac.2024.131468 -
Scientific Reports Apr 2024Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia....
Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (- 0.186 µM, - 1.267 µM) and ki' (- 0.691 µM, - 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110-115 mg/dL), increased insulin level (25-30 μM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.
Topics: Mice; Animals; Hypoglycemic Agents; alpha-Glucosidases; Molecular Docking Simulation; Hyperglycemia; Insulin; alpha-Amylases; Glycoside Hydrolase Inhibitors; Structure-Activity Relationship
PubMed: 38565861
DOI: 10.1038/s41598-023-49932-2 -
Frontiers in Endocrinology 2024Obesity, prevalent in approximately 80% of Qatar's adult population, increases the risk of complications like type 2 diabetes and cardiovascular diseases. Predictive...
INTRODUCTION
Obesity, prevalent in approximately 80% of Qatar's adult population, increases the risk of complications like type 2 diabetes and cardiovascular diseases. Predictive biomarkers are crucial for preventive strategies. Salivary α-amylase activity (sAAa) inversely correlates with obesity and insulin resistance in adults and children. However, the connection between sAAa and cardiometabolic risk factors or chronic low-grade inflammation markers remains unclear. This study explores the association between serum sAAa and adiposity markers related to cardiovascular diseases, as well as markers indicative of chronic low-grade inflammation.
METHODS
Serum samples and clinical data of 1500 adult, non-diabetic, Overweight/Obese participants were obtained from Qatar Biobank (QBB). We quantified sAAa and C reactive protein (CRP) levels with an autoanalyzer. Cytokines, adipokines, and adiponectin of a subset of 228 samples were quantified using a bead-based multiplex assay. The associations between the sAAa and the adiposity indices and low-grade inflammatory protein CRP and multiple cytokines were assessed using Pearson's correlation and adjusted linear regression.
RESULTS
The mean age of the participants was 36 ± 10 years for both sexes of which 76.6% are women. Our analysis revealed a significant linear association between sAAa and adiposity-associated biomarkers, including body mass index β -0.032 [95% CI -0.049 to -0.05], waist circumference β -0.05 [95% CI -0.09 to -0.02], hip circumference β -0.052 [95% CI -0.087 to -0.017], and HDL β 0.002 [95% CI 0.001 to 0.004], albeit only in women. Additionally, sAAa demonstrated a significant positive association with adiponectin β 0.007 [95% CI 0.001 to 0.01]while concurrently displaying significant negative associations with CRP β -0.02 [95% CI -0.044 to -0.0001], TNF-α β -0.105 [95% CI -0.207 to -0.004], IL-6 β [95% CI -0.39 -0.75 to -0.04], and ghrelin β -5.95 [95% CI -11.71 to -0.20], specifically within the female population.
CONCLUSION
Our findings delineate significant associations between sAAa and markers indicative of cardiovascular disease risk and inflammation among overweight/obese adult Qatari females. Subsequent investigations are warranted to elucidate the nuances of these gender-specific associations comprehensively.
Topics: Male; Adult; Child; Humans; Female; Middle Aged; Overweight; Salivary alpha-Amylases; Adiponectin; Diabetes Mellitus, Type 2; Cardiovascular Diseases; Obesity; Biomarkers; Inflammation; Cytokines
PubMed: 38562410
DOI: 10.3389/fendo.2024.1348853