► Norton grape skin (GSE) inhibits yeast and rat α-glucosidases. ► Norton GSE does not significantly inhibit pancreatic α-amylase. ► Norton GSE reduced postprandial blood glucose in mice.
Intestinal ...α-glucosidases are the key enzymes responsible for starch digestion and absorption and their inhibition has been proven effective in both preventing and treating diabetes through improvement of postprandial hyperglycaemia. This study, for the first time, identified that a Norton grape skin extract (GSE) significantly inhibited mammalian intestinal α-glucosidases but not other digestive enzymes including structurally relevant pancreatic α-amylase. Norton GSE inhibited rat intestinal α-glucosidases through a competitive mode with an IC50 of 0.384mg/ml. Further animal study revealed that the oral intake of Norton GSE (400mg/kg) significantly reduced postprandial blood glucose by 30.9% in the streptozocin-treated male C57BL/6J mice following starch challenge. These findings suggest that Norton GSE may have a unique property of suppressing postprandial blood glucose through a mechanism involving the inhibition of α-glucosidases, thereby providing a novel dietary opportunity for diabetes management.
Introduction: Pompe disease (PD) is a rare metabolic disorder caused by a partial or complete deficiency of acid α-glucosidase (GAA) which leads to lysosomal accumulation of glycogen. Excessive ...amounts of glycogen accumulate mainly in the cells of the heart and skeletal muscles and cause dysfunction of these tissues. It is inherited in an autosomal recessive manner. The most common diagnostic methods include genetic tests and the measurement of enzyme activity in leukocytes or fibroblasts. A screening test is also available that tests the enzyme activity in dried blood spot (DBS). The treatment of PD is mostly based on synthetic GAA enzyme supply to the patients. The therapy reduces glycogen storage and improves muscle function, decreases heart size and prolongs the lives of those with infantile form of PD. In the adult onset of the disease treatment increases physical efficiency and reduces the progression of respiratory failure.
Aim of the study: Systematization of current knowledge about Pompe disease with particular emphasis on possible clinical presentations, diagnostics and therapeutic options.
Material and methods: Literature review based on PubMed data using the following keywords: Pompe disease, Glycogenosis type ii, glucosidase alpha
Summary : Pompe disease is a rare disease with many problems related to diagnosis and possible therapies. Its symptoms can be very misleading and cause a delay in diagnosis . It is critical to start the therapy as soon as possible to best manage the disease. The prognosis of PD is poor, especially in children under 12 months of age. Gene therapy research is currently underway and early results are very promising. There is still much to learn about dealing with this disease.
A total of 77% of consecutive pneumatosis intestinalis (PI) patients were attributable to non‐ischaemic underlying disease. PI patients with bowel ischaemia showed high mortality even with emergency ...surgery. A total of 60% of PI patients with bowel resection and primary anastomosis experienced leak.
Background
Several theories explaining the development of pneumatosis intestinalis (PI) have been reported, but a substantial portion of cases have been idiopathic. Additionally, predictors of bowel ischaemia in PI have not been fully investigated, while PI with bowel ischaemia has deteriorated overall outcomes of PI.
Methods
Sixty‐four patients diagnosed with PI (2009–2019) were allocated to two groups: with (group 1; n = 15 (23%)) and without (group 2; n = 49 (77%)) bowel ischaemia. Fourteen patients underwent emergency surgery, and bowel ischaemia was identified in nine (64%). Six patients in group 1 were diagnosed with bowel ischaemia, and were treated palliatively. On medical charts, we determined underlying conditions of PI, compared the characteristics and outcomes between the groups, and identified the predictors of bowel ischaemia.
Results
Group 1 patients more commonly showed abdominal pain, lower base excess, higher C‐reactive protein concentrations, higher white blood cell counts and higher neutrophil‐to‐lymphocyte ratios, and more frequent comorbid ascites, free air and hepatic portal vein gas. Of nine bowel ischaemia surgery patients, three (33%) died; all because of anastomotic leak. All except three patients in group 2, who presented with aspiration pneumonia, responded to treatment. Only one patient had an unknown cause (1/64, 1.6%), and various underlying conditions in secondary PI were confirmed.
Conclusion
Idiopathic PI may be identified rarely using current imaging and knowledge, but outcomes in PI patients with bowel ischaemia remain unsatisfactory. Earlier identification of bowel ischaemia by various specialists in accordance with predictors of bowel ischaemia could improve overall outcomes in PI patients.
A new class of triazinoindole-bearing thiosemicarbazides (
-
) was synthesized and evaluated for α-glucosidase inhibitory potential. All synthesized analogs exhibited excellent inhibitory potential, ...with IC
values ranging from 1.30 ± 0.01 to 35.80 ± 0.80 µM when compared to standard acarbose (an IC
value of 38.60 ± 0.20 µM). Among the series, analogs
and
were found to be the most potent, with IC
values of 1.30 ± 0.05 and 1.30 ± 0.01 µM, respectively. The structure-activity relationship (SAR) was mainly based upon bringing about different substituents on the phenyl rings. To confirm the binding interactions, a molecular docking study was performed.
Calystegines are polyhydroxylated nortropane alkaloids found in Convolvulaceae, Solanaceae, and other plant families. These plants produce common fruits and vegetables. The calystegine structures ...resemble sugars and suggest interaction with enzymes of carbohydrate metabolism. Maltase and sucrase are α-glucosidases contributing to human carbohydrate degradation in the small intestine. Inhibition of these enzymes by orally administered drugs is one option for treatment of diabetes mellitus type 2. In this study, inhibition of maltase and sucrase by calystegines A3 and B2 purified from potatoes was investigated. In silico docking studies confirmed binding of both calystegines to the active sites of the enzymes. Calystegine A3 showed low in vitro enzyme inhibition; calystegine B2 inhibited mainly sucrose activity. Both compounds were not transported by Caco-2 cells indicating low systemic availability. Vegetables rich in calystegine B2 should be further investigated as possible components of a diet preventing a steep increase in blood glucose after a carbohydrate-rich meal.
(
) is an
herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the α-glucosidase inhibitory activity of
leaves extracts, ...and to identify the metabolites responsible for the bioactivity.
Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their α-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS).
Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure
isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding.
The study provides informative data on the potential α-glucosidase inhibitors identified in
leaves, indicating the plant's therapeutic effect to manage hyperglycemia.
Solanum anomalum Thonn. ex Schumach. (family Solanaceae), an edible shrub whose fruits and leaves are used medicinally to treat diseases including diabetes was evaluated for effect on alpha amylase ...and alpha glucosidase enzymes in vivo. The leaf extract (70-210 mg/kg) and fractions (hexane, dichloromethane, ethyl acetate, methanol, 140 mg/kg) of S. anomalum were evaluated in vivo for inhibitory effect on alpha amylase and alpha glucosidase enzymes using starch, sucrose and maltose as substrates. Acarbose was used as reference drug. The leaf extract especially middle dose (140 mg/kg) and fractions (ethyl acetate and hexane) caused significant (p<0.05) reduction in blood glucose levels of treated with the various substrates used. Ethyl acetate fraction exerted the highest inhibitory effect when starch and maltose were used as substrates followed by n-hexane and methanol. n-Hexane was the most active fraction followed by ethyl acetate when sucrose was used as substrate. The results suggest that the leaf extract and fractions of S. anomalum have the potentials to inhibit alpha amylase and glucosidase in rats.
Xanthohumol (XN) is a unique prenylated flavonoid in hops (Humulus lupulus L.) and beer. XN alleviates hyperglycemia and has potential usage in the treatment of type 2 diabetes. In the present study, ...a series of in vitro experiments were performed to investigate whether XN was an effective inhibitor of α-glucosidase. The results showed that XN inhibited α-glucosidase in a reversible and noncompetitive manner, with an IC50 value of 8.8 μM and that XN inhibited the release of glucose from the maltose in the apical side of the Caco-2 cell monolayer. Fluorescence and circular dichroism spectra results indicated that XN directly bound to α-glucosidase and induced minor conformational changes of the enzyme. These results demonstrated that XN is a promising α-glucosidase inhibitor, which therefore could be used as functional food to alleviate postprandial hyperglycemia and as a potential candidate for the development of an antidiabetic agent.
The alpha-glucosidase enzyme of Candida albicans plays a vital role in the pathogenesis of candidiasis, a serious fatal disease in immune-compromised patients. The unavailability of the ...threedimensional crystallographic structure of this enzyme creates a hindrance in developing novel and potent inhibitors. Here, an attempt has been made to design a stable three-dimensional conformer of alpha-glucosidase through in silico analysis which may be helpful for the designing of effective drugs. For this purpose, the oligo-1-6-glucosidase enzyme is used as a template for homology modeling of the alpha-glucosidase structure by Molecular Operating Environment 2011-12 software. The generated model was validated through ERRAT and Ramachandran tools, whereas its stability was studied through the molecular dynamics simulation technique. The obtained results indicate that model of alpha-glucosidase has stable secondary and tertiary arrangements. This finding may spur new directions for the rational designing and development of new antifungal inhibitors. Nevertheless, additional experimental investigations and validation are needed to confirm the in silico results of this study.
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