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PloS One 2022α-glucosidase inhibitors represent an important class of type 2 antidiabetic drugs and they act by lowering postprandial hyperglycemia. Today, only three synthetic...
α-glucosidase inhibitors represent an important class of type 2 antidiabetic drugs and they act by lowering postprandial hyperglycemia. Today, only three synthetic inhibitors exist on the market, and there is a need for novel, natural and more efficient molecules exhibiting this activity. In this study, we investigated the ability of Tamarix nilotica ethanolic and aqueous shoot extracts, as well as methanolic fractions prepared from aqueous crude extracts to inhibit α-glucosidase. Both, 50% ethanol and aqueous extracts inhibited α-glucosidase in a concentration-dependent manner, with IC50 values of 12.5 μg/mL and 24.8 μg/mL, respectively. Importantly, α-glucosidase inhibitory activity observed in the T. nilotica crude extracts was considerably higher than pure acarbose (IC50 = 151.1 μg/mL), the most highly prescribed α-glucosidase inhibitor on the market. When T. nilotica crude extracts were fractionated using methanol, enhanced α-glucosidase inhibitory activity was observed in general, with the highest observed α-glucosidase inhibitory activity in the 30% methanol fraction (IC50 = 5.21 μg/mL). Kinetic studies further revealed a competitive reversible mechanism of inhibition by the plant extract. The phytochemical profiles of 50% ethanol extracts, aqueous extracts, and the methanolic fractions were investigated and compared using a metabolomics approach. Statistical analysis revealed significant differences in the contents of the crude extracts and fractions and potentially identified the molecules that were most responsible for these observed variations. Higher α-glucosidase inhibitory activity was associated with an enrichment of terpenoids, fatty acids, and flavonoids. Among the identified molecules, active compounds with known α-glucosidase inhibitory activity were detected, including unsaturated fatty acids, triterpenoids, and flavonoid glycosides. These results put forward T. nilotica as a therapeutic plant for type 2 diabetes and a source of α-glucosidase inhibitors.
Topics: Diabetes Mellitus, Type 2; Ethanol; Flavonoids; Glycoside Hydrolase Inhibitors; Kinetics; Methanol; Plant Extracts; Tamaricaceae; alpha-Glucosidases
PubMed: 35286313
DOI: 10.1371/journal.pone.0264969 -
Molecules (Basel, Switzerland) Jan 2019Momilactones A (MA) and B (MB) are the active phytoalexins and allelochemicals in rice. In this study, MA and MB were purified from rice husk of cv. Koshihikari by...
Momilactones A (MA) and B (MB) are the active phytoalexins and allelochemicals in rice. In this study, MA and MB were purified from rice husk of cv. Koshihikari by column chromatography, and purification was confirmed by high-performance liquid chromatography, thin-layer chromatography, gas chromatography-mass spectrometry, liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS), and ¹H and C nuclear magnetic resonance analyses. By in vitro assays, both MA and MB exerted potent inhibition on α-amylase and α-glucosidase activities. The inhibitory effect of MB on these two key enzymes was greater than that of MA. Both MA and MB exerted greater α-glucosidase suppression as compared to that of the commercial diabetic inhibitor acarbose. Quantities of MA and MB in rice grain were 2.07 ± 0.01 and 1.06 ± 0.01 µg/dry weight (DW), respectively. This study was the first to confirm the presence of MA and MB in refined rice grain and reported the α-amylase and α-glucosidase inhibitory activity of the two compounds. The improved protocol of LC-ESI-MS in this research was simple and effective to detect and isolate MA and MB in rice organs.
Topics: Amylases; Diterpenes; Glycoside Hydrolase Inhibitors; Lactones; Oryza; alpha-Amylases; alpha-Glucosidases
PubMed: 30700006
DOI: 10.3390/molecules24030482 -
Nutrients Feb 2022Inhibiting α-glucosidase activity is important in controlling postprandial hyperglycemia and, thus, helping to manage type-2 diabetes mellitus (T2DM). In the present...
Inhibiting α-glucosidase activity is important in controlling postprandial hyperglycemia and, thus, helping to manage type-2 diabetes mellitus (T2DM). In the present study, free polyphenols (FPE) and bound polyphenols (BPE) were extracted from red quinoa and their inhibitory effects on α-glucosidase and postprandial glucose, as well as related mechanisms, were investigated. HPLC-MS analysis showed that the components of FPE and BPE were different. FPE was mainly composed of hydroxybenzoic acid and its derivatives, while BPE was mainly composed of ferulic acid and its derivatives. BPE exhibited stronger DPPH and ABTS antioxidant activities, and had a lower IC50 (10.295 mg/mL) value in inhibiting α-glucosidase activity. The inhibition kinetic mode analysis revealed that FPE and BPE inhibited α-glucosidase in a non-competitive mode and an uncompetitive mode, respectively. Furthermore, compared to FPE, BPE delayed starch digestion more effectively. BPE at 50 mg/kg reduced postprandial glucose increases comparably to acarbose at 20 mg/kg in ICR mice. These results could provide perspectives on the potential of BPE from red quinoa, as a functional food, to inhibit α-glucosidase activity, delay postprandial glucose increases and manage T2DM.
Topics: Animals; Blood Glucose; Chenopodium quinoa; Digestion; Glycoside Hydrolase Inhibitors; Mice; Mice, Inbred ICR; Polyphenols; Starch; alpha-Glucosidases
PubMed: 35215378
DOI: 10.3390/nu14040728 -
Protein Science : a Publication of the... Aug 2018Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures...
Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the antidiabetic α-glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro-αG1 suggests the potential for unintended in vivo crossreaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug-bound enzyme structures could benefit further antidiabetic drug development.
Topics: 1-Deoxynojirimycin; Bacterial Proteins; Gastrointestinal Microbiome; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Models, Molecular; Protein Binding; Ruminococcus; alpha-Glucosidases
PubMed: 29761590
DOI: 10.1002/pro.3444 -
Molecules (Basel, Switzerland) Apr 2024The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones....
The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds (), (), (), (), (), () and () were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12--tetradecanoylphorbol 13-acetate) on mouse ears; compounds - were tested at 10 µg/ear dose. As a result, , , and show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.
Topics: Glycoside Hydrolase Inhibitors; Anti-Inflammatory Agents; Lactams; Animals; alpha-Glucosidases; Molecular Docking Simulation; Mice; Structure-Activity Relationship; Computer Simulation; Edema; Molecular Structure
PubMed: 38731463
DOI: 10.3390/molecules29091973 -
Molecules (Basel, Switzerland) Sep 2021α-Glucosidase was immobilized on magnetic nanoparticles (MNPs) for selective solid-phase extraction of the enzyme's ligands present in , which is a medicinal plant used...
α-Glucosidase was immobilized on magnetic nanoparticles (MNPs) for selective solid-phase extraction of the enzyme's ligands present in , which is a medicinal plant used for the treatment of various diseases and possesses anti-diabetic activity. One new compound, aloeacone (), together with two known compounds, aloenin aglycone () and aloin A (), were fished out as the enzyme's ligands. The structure of was determined by HR-MS and comprehensive NMR techniques. Compound exhibited a weak inhibitory effect on α-glucosidase, while compounds and were found to possess activation effects on the enzyme for the first time. It is interesting that both an inhibitor and agonists of α-glucosidase were fished out in one experiment.
Topics: Aloe; Cathartics; Emodin; Enzymes, Immobilized; Glucosides; Ligands; Magnetite Nanoparticles; Plant Extracts; alpha-Glucosidases
PubMed: 34641385
DOI: 10.3390/molecules26195840 -
Molecules (Basel, Switzerland) Feb 2020The alpha-glucosidase- and lipase-inhibitory activities of three phenalenones (-) and one phenylpropanoid () from the ethyl acetate extracts of a sp. are described....
The alpha-glucosidase- and lipase-inhibitory activities of three phenalenones (-) and one phenylpropanoid () from the ethyl acetate extracts of a sp. are described. They represent the first secondary metabolites reported from the genus . Scleroderolide () and sclerodione () exhibited potent α-glucosidase- and porcine-lipase-inhibitory activity during primary screening, with better IC values compared to the positive controls, N-deoxynojirimycin and orlistat. In silico techniques were employed to validate the probable biological targets and elucidate the mechanism of actions of phenalenones and . Both compounds exhibited strong binding affinities to both alpha-glucosidase and porcine lipase through H-bonding and π-π interactions. Interestingly, favorable in silico ADME (absorption, distribution, metabolism, and excretion) properties such as gastrointestinal absorption were also predicted using software.
Topics: Animals; Ascomycota; Glycoside Hydrolase Inhibitors; Lipase; Molecular Docking Simulation; Phenalenes; Swine; Thailand; alpha-Glucosidases
PubMed: 32093426
DOI: 10.3390/molecules25040965 -
Molecules (Basel, Switzerland) Jan 2022Wall. (Convolvulaceae) is wildly distributed in Asia. Its stem is used as the component in traditional Thai recipes for treatments of muscle rigidity, skin disorder,...
Wall. (Convolvulaceae) is wildly distributed in Asia. Its stem is used as the component in traditional Thai recipes for treatments of muscle rigidity, skin disorder, dysentery, and hypoglycemia. However, the chemical constituents and biological activities of have not been reported. From a screening assay, stem crude extract showed the potent effect on alpha-glucosidase inhibition at 2 mg/mL as 96.09%. The bioassay-guiding isolation led to 5 compounds that were identified by spectroscopic techniques as scopoletin (), syringic acid (), methyl 3-methyl-2-butenoate (), feruloyltyramine (), and coumaroyltyramine (). Compounds , , and exhibited an IC of 110.97, 29.87, and 0.92 µg/mL, respectively, while the IC of positive standard, acarbose was 272.72 µg/mL. Kinetic study showed that compound performed as the mixed-type inhibition mechanism, whereas compounds and displayed the uncompetitive inhibition mechanism. The docking study provided the molecular understanding of isolated aromatic compounds (, , and ) to alpha-glucosidase. Hence, this study would be the first report of isolated compounds and their anti-alpha-glucosidase activity with the mechanism of action from . Thus, these active compounds will be further studied to be the lead compounds among natural antidiabetic drugs.
Topics: Convolvulaceae; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Molecular Docking Simulation; Plant Extracts; Plants, Medicinal; Thailand; alpha-Glucosidases
PubMed: 35163903
DOI: 10.3390/molecules27030639 -
Molecules (Basel, Switzerland) Aug 2021The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be...
The inhibition of α-glucosidase is a clinical strategy for the treatment of type 2 diabetes mellitus (T2DM), and many natural plant ingredients have been reported to be effective in alleviating hyperglycemia by inhibiting α-glucosidase. In this study, the α-glucosidase inhibitory activity of fisetin extracted from Scop. was evaluated in vitro. The results showed that fisetin exhibited strong inhibitory activity with an IC value of 4.099 × 10 mM. Enzyme kinetic analysis revealed that fisetin is a non-competitive inhibitor of α-glucosidase, with an inhibition constant value of 0.01065 ± 0.003255 mM. Moreover, fluorescence spectrometric measurements indicated the presence of only one binding site between fisetin and α-glucosidase, with a binding constant (lgKa) of 5.896 L·mol. Further molecular docking studies were performed to evaluate the interaction of fisetin with several residues close to the inactive site of α-glucosidase. These studies showed that the structure of the complex was maintained by Pi-Sigma and Pi-Pi stacked interactions. These findings illustrate that fisetin extracted from Scop. is a promising therapeutic agent for the treatment of T2DM.
Topics: Diabetes Mellitus, Type 2; Flavonols; Glycoside Hydrolase Inhibitors; Humans; Molecular Docking Simulation; alpha-Glucosidases
PubMed: 34500738
DOI: 10.3390/molecules26175306 -
Marine Drugs Dec 2022Three new dibenzo--pyrone derivatives, alternolides A-C (-), and seven known congeners (-) were isolated from the marine-derived fungus of LW37 assisted by the one...
Three new dibenzo--pyrone derivatives, alternolides A-C (-), and seven known congeners (-) were isolated from the marine-derived fungus of LW37 assisted by the one strain-many compounds (OSMAC) strategy. The structures of - were established by extensive spectroscopic analyses, and their absolute configurations were determined by modified Snatzke's method and electronic circular dichroism (ECD) calculations. Compounds and showed good 1,1-diphenyl-2-picrylhydrazyl (DPPH) antioxidant scavenging activities with IC values of 83.94 ± 4.14 and 23.60 ± 1.23 µM, respectively. Additionally, , and exhibited inhibitory effects against -glucosidase with IC values of 725.85 ± 4.75, 451.25 ± 6.95 and 6.27 ± 0.68 µM, respectively. The enzyme kinetics study indicated and were mixed-type inhibitors of -glucosidase with values of 347.0 and 108.5 µM, respectively. Furthermore, the interactions of , and with -glucosidase were investigated by molecular docking.
Topics: alpha-Glucosidases; Pyrones; Molecular Docking Simulation; Alternaria; Antioxidants; Molecular Structure; Glycoside Hydrolase Inhibitors
PubMed: 36547925
DOI: 10.3390/md20120778