Jacq. (Solanaceae) is widely found in South East Asia. In Thailand, it is used as vegetable and as a component in traditional recipes. The results of an alpha-glucosidase inhibitory screening test ...found that the crude extract of
inflorescence exhibited the potential effect with IC
81.27 μg/mL. The separation was performed by the increasing solvent polarity method. The ethyl acetate, ethanol, and water extracts of
inflorescence showed the synergistic effect together with acarbose standard. The phytochemical investigation of these extracts was conducted by chromatographic and spectroscopic techniques. Six flavonoid compounds, myricetin 3, 4', 5', 7-tetramethyl ether (
), combretol (
), kaempferol (
), kaempferol 7-
-glucopyranoside (
), 5-hydroxy 3-7-4'-5'-tetramethoxyflavone-3'-
-glucopyranoside (
), and a mixture (
) of isorhamnetin 3-
-glucopyranoside (
) and astragalin (
) were isolated. This discovery is the first report of flavonoid-glycoside
. Moreover, the selected flavonoids, kaempferol and astragalin, were representatives to explore the mechanism of action. Both of them performed mixed-type inhibition. The molecular docking gave a better understanding of flavonoid compounds' ability to inhibit the alpha-glucosidase enzyme.
Objective: Peperomia is a genus belong to Piperaceae family, which is valuable as ornamental and has several medical uses but not widely explored in their pharmacological activities. Some peperomia ...plant has been investigated and reported to have various activities, recently as diabetes mellitus. This research was conducted to screening phytochemical profile and to determine alpha-glucosidase inhibitor activities of five species in genus Peperomia that are easy to grow and has been cultivated in Indonesia.
Methods: Dried leaves were macerated with 70% ethanol and vaporized by rotary evaporator. Phytochemical screening was conducted using qualitative chemical analysis and inhibition of alpha-glucosidase was conducted using p-nitrophenyl-α-D-glucopyranoside as substrate, and absorbance was measured with a spectrophotometer UV-Vis.
Results: The phytochemical screening of the leaves extracts demonstrated the presence of various secondary metabolites, such as flavonoids, phenol, tannins, quinone, alkaloids, saponins, steroids, and triterpenoids. The inhibition of alpha-glucosidase showed that the IC50 value of ethanol extract of P. obtusifolia, P. clusiifolia, P. caperata (green), P. caperata (red), and P. argyreia leaves were 2.90; 18.05; 21.46; 23.81; and 48.70 µg/ml respectively.
Conclusion: The highest inhibition of alpha-glucosidase activity was showed by P. obtusifolia with an IC50 value of 2.90 µg/ml. Further research is needed to explore its potential as an antidiabetic.
Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) that could offer ...great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA) against both aquaporin (AQP) and a sucrase gene, alpha glucosidase (AGLU). These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RTqPCR) was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci) and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that downregulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops.
The structures of the E277A isomaltase mutant from
Saccharomyces cerevisiae in complex with isomaltose or maltose were determined at resolutions of 1.80 and 1.40
Å, respectively. The root mean square ...deviations between the corresponding main-chain atoms of free isomaltase and the E277Α-isomaltose complex structures and those of free isomaltase and the E277A-maltose complex structures were found to be 0.131
Å and 0.083
Å, respectively. Thus, the amino acid substitution and ligand binding do not affect the overall structure of isomaltase. In the E277A-isomaltose structure, the bound isomaltose was readily identified by electron densities in the active site pocket; however, the reducing end of maltose was not observed in the E277A-maltose structure. The superposition of maltose onto the E277A-maltose structure revealed that the reducing end of maltose cannot bind to the subsite +
1 due to the steric hindrance from Val216 and Gln279. The amino acid sequence comparisons with α-glucosidases showed that a bulky hydrophobic amino acid residue is conserved at the position of Val216 in α-1,6-glucosidic linkage hydrolyzing enzymes. Similarly, a bulky amino acid residue is conserved at the position of Gln279 in α-1,6-glucosidic linkage-only hydrolyzing α-glucosidases. Ala, Gly, or Asn residues were located at the position of α-1,4-glucosidic linkage hydrolyzing α-glucosidases. Two isomaltase mutant enzymes – V216T and Q279A – hydrolyzed maltose. Thus, the amino acid residues at these positions may be largely responsible for determining the substrate specificity of α-glucosidases.
This study synthesized a series of hydroxyl-functionalized 2-arylbenzobfurans based on the structure of tournefolic acid A and evaluated them for antioxidant and α-glucosidase inhibitory activities. ...Compounds 5a, 5e, and 5n showed remarkable inhibition of α-glucosidase (IC50 values of 1.9–3.0 μM), and they appear to be even more potent than quercetin. A kinetic binding study indicated that compounds 5a and 5n used a mechanism of mixed-competition to inhibit α-glucosidase. This study also revealed that compounds 5a and 5n bind to either the α-glucosidase or α-glucosidase-4-NPGP complex. Using the crystal structure of the Saccharomyces cerevisiae α-glucosidase, the molecular docking study has predicted the binding of compounds 5a and 5n to the active site of α-glucosidase through both hydrophobic and hydrogen interactions. A DPPH radical scavenging assay further showed that most hydroxyl-functionalized 2-arylbenzobfurans possess antioxidant activity. The exception was compound 5p, which has only one hydroxyl group on the 2-phenyl ring of 2-arylbenzobfuran. Our results indicate that hydroxyl-functionalized 2-arylbenzobfurans possess both antidiabetic as well as antioxidant properties.
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•A series of new hydroxyl-functionalized 2-arylbenzobfurans has synthesized.•Antioxidant and α-glucosidase inhibition activities.•Inhibition kinetics of new compounds were determined.•Molecular docking study predicted the binding of compounds to α-glucosidase.
Introduction: Pompe disease is a rare, autosomal recessive disorder caused by deficiency of the glycogen‐degrading lysosomal enzyme acid alpha‐glucosidase. Late‐onset Pompe disease is a multisystem ...condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders. Methods: Objective is to propose consensus‐based treatment and management recommendations for late‐onset Pompe disease. Methods: A systematic review of the literature by a panel of specialists with expertise in Pompe disease was undertaken. Conclusions: A multidisciplinary team should be involved to properly treat the pulmonary, neuromuscular, orthopedic, and gastrointestinal elements of late‐onset Pompe disease. Presymptomatic patients with subtle objective signs of Pompe disease (and patients symptomatic at diagnosis) should begin treatment with enzyme replacement therapy (ERT) immediately; presymptomatic patients without symptoms or signs should be observed without use of ERT. After 1 year of ERT, patients' condition should be reevaluated to determine whether ERT should be continued. Muscle Nerve, 2012
The Lantern Project is an ongoing complimentary diagnostic program for patients in the United States sponsored by Sanofi and implemented by PerkinElmer Genomics. It combines specific enzymatic, ...biomarker, and genetic testing to facilitate rapid, accurate laboratory diagnosis of Pompe disease and several other lysosomal storage diseases, and a multigene next-generation sequencing panel including Pompe disease, LGMD, and other neuromuscular disorders. This article reports data for Pompe disease collected from October 2018 through December 2021, including acid α-glucosidase (GAA) enzyme assay and GAA sequencing (standard or expedited for positive newborn screening NBS to rule out infantile-onset Pompe disease IOPD) and the Focused Neuromuscular Panel, which includes GAA. One hundred forty patients (12 received only GAA enzyme testing, 128 had GAA sequencing alone or in addition to enzyme assay) have been confirmed with Pompe disease in this project. Eight of the 140 had a variant of unknown significance, but GAA activity ≤2.10 μmol/L/h, thus were confirmed with Pompe disease. Three diagnosed patients 0–2 years old had cross-reactive immunologic material (CRIM)-negative GAA variants and thus IOPD. One additional infant with presumptive IOPD had a homozygous frameshift c.1846del, likely CRIM-negative; symptoms were not provided. Among the 128 patients with molecular results, the c.-32-13T>G splice variant was homozygous in 11, compound-heterozygous in 98, and absent in 19. Proximal muscle weakness (58 patients) was the most common sign reported at testing; elevated creatine kinase (29 patients) was the most common laboratory result. The most common symptom categories were muscular (73 patients), musculoskeletal (13 patients), and respiratory (23 patients). Clinical information was not available for 42 samples, and 17 infants had only “abnormal NBS” or “low GAA” reported. Cardiac symptoms in 7 included potentially age-related conditions in five c.-32-13T>G-compound-heterozygous adults (myocardial infarction, heart murmur/palpitations, congestive heart failure: 1 each; 2 with atrial fibrillation) and hypertrophic cardiomyopathy in 2 children (1 and 2 years old) with presumptive IOPD. One novel GAA variant was observed in a patient with enzyme activity 0.31 μmol/L/h: c.1853_1854ins49, a frameshift pathogenic variant. The Lantern Project demonstrates the combinatorial utility of enzyme assay, targeted single-gene testing, and a focused neuromuscular next-generation sequencing panel in diagnosing Pompe disease.
•Lantern Project provides enzyme, molecular, and NGS panel options for Pompe disease.•In 2018–21, 6473 panel tests and 1339 targeted tests have been conducted.•140 patients received a laboratory diagnosis of Pompe disease.•Enzyme activity informed several VUS alleles; one novel frameshift allele reported.•One patient each had an DMD or ANO5 variant along with GAA pathogenic/VUS alleles.
•First study on the phenolic compounds in a purple hybrid passion fruit peel.•Evaluated the bioactivities of ethanol extracts from passion fruit peel (PFPE).•Stabilities and bioactivities of PFPE ...were affected by simulated digestive process.•PFPE alpha-glucosidase inhibition capacity decreased after in vitro digestion.•PFPE anthocyanins had the highest correlation with alpha-glucosidase inhibition.
Passion fruit peel, a potential source of bioactive compounds, has been used as food stabilizing agent. However, the phenolic composition and bioactivity of passion fruit peel have rarely been reported. The effects of simulated gastrointestinal digestion on the bioactive components, bioactivity and bioaccessibility of passion fruit peel ethanol extracts (PFPE) were investigated using high performance liquid chromatography-tandem mass spectrometry analysis (quasi-targeted metabolomics). Phenols (178) were identified, of which 25 inhibited alpha-glucosidase activity. The stabilities of PFPE phenols were significantly affected by pH changes and digestive enzymes during simulated digestion. The 1,1-diphenyl-2-picrylhydrazyl free radical scavenging capacity and ferric ion reducing antioxidant power were decreased by 32% and 30%, respectively, while 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity increased by 17%. Alpha-glucosidase inhibition decreased with decreased PFPE phenolic content. Therefore, passion fruit peel could be considered a source of natural antioxidants and alpha-glucosidase inhibitors.
For digestion of starch in humans, α-amylase first hydrolyzes starch molecules to produce α-limit dextrins, followed by complete hydrolysis to glucose by the mucosal α-glucosidases in the small ...intestine. It is known that α-1,6 linkages in starch are hydrolyzed at a lower rate than are α-1,4 linkages. Here, to create designed slowly digestible carbohydrates, the structure of waxy corn starch (WCS) was modified using a known branching enzyme alone (BE) and an in combination with β-amylase (BA) to increase further the α-1,6 branching ratio. The digestibility of the enzymatically synthesized products was investigated using α-amylase and four recombinant mammalian mucosal α-glucosidases. Enzyme-modified products (BE-WCS and BEBA-WCS) had increased percentage of α-1,6 linkages (WCS: 5.3%, BE-WCS: 7.1%, and BEBA-WCS: 12.9%), decreased weight-average molecular weight (WCS: 1.73×10 8 Da, BE-WCS: 2.76×10 5 Da, and BEBA-WCS 1.62×10 5 Da), and changes in linear chain distributions (WCS: 21.6, BE-WCS: 16.9, BEBA-WCS: 12.2 DP w). Hydrolysis by human pancreatic α-amylase resulted in an increase in the amount of branched α-limit dextrin from 26.8% (WCS) to 56.8% (BEBA-WCS). The α-amylolyzed samples were hydrolyzed by the individual α-glucosidases (100 U) and glucogenesis decreased with all as the branching ratio increased. This is the first report showing that hydrolysis rate of the mammalian mucosal α-glucosidases is limited by the amount of branched α-limit dextrin. When enzyme-treated materials were gavaged to rats, the level of postprandial blood glucose at 60 min from BEBA-WCS was significantly higher than for WCS or BE-WCS. Thus, highly branched glucan structures modified by BE and BA had a comparably slow digesting property both in vitro and in vivo . Such highly branched α-glucans show promise as a food ingredient to control postprandial glucose levels and to attain extended glucose release.
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