- Digestibility of fucosylated glycosaminoglycan from sea cucumber and its effects on digestive enzymes under simulated salivary and gastrointestinal conditions. [Journal Article]
- CPCarbohydr Polym 2018 Apr 15; 186:217-225
- The digestibility of fucosylated glycosaminoglycan (FG) and its effects on digestive enzymes were investigated using an in vitro digestion model. Results showed that the molecular weight and the redu...
The digestibility of fucosylated glycosaminoglycan (FG) and its effects on digestive enzymes were investigated using an in vitro digestion model. Results showed that the molecular weight and the reducing sugar content of FG were not significantly changed, and no free monosaccharides released from FG were detected after the salivary, gastric and intestinal digestion, indicating that both the backbone and the sulfated fucose branches of FG are resistant to be cleaved in the saliva and gastrointestinal tract environments. Furthermore, FG can dose-dependently inhibit digestive enzymes such as α-amylase, pepsin and pancreatic lipase in different degrees under the simulated digestion conditions due to the sulfate and carboxyl groups. These physiological effects of FG may help control the postprandial glucose concentration and have the potential in the prevention or treatment of reflux disease and obesity. The findings may provide information on the digestibility and beneficial physiological effects of FG as a potential natural product to promote human health.
- Evaluation of α-glucosidase inhibiting potentials with docking calculations of synthesized arylidene-pyrazolones. [Journal Article]
- BCBioorg Chem 2018 Feb 10; 77:507-514
- Herein, condensation of aryl(hetaryl)pyrazole-4-carbaldehydes 1(a-c) with substituted pyrazolones 2(a-d) lead to the corresponding arylidene-pyrazolones 3(a-l) which were tested against α-glucosidase...
Herein, condensation of aryl(hetaryl)pyrazole-4-carbaldehydes 1(a-c) with substituted pyrazolones 2(a-d) lead to the corresponding arylidene-pyrazolones 3(a-l) which were tested against α-glucosidase enzyme. The synthesized compounds displayed moderate to good activity. Among these, a coumarin derivative 3k exhibited excellent results (IC502.10 ± 0.004 µM) in comparison to clinical drug acarbose (IC5037.38 ± 0.12 µM). The ligand-protein interactions were identified through docking and stabilizing energy calculations.
- Moringa oleifera supplemented diet modulates nootropic-related biomolecules in the brain of STZ-induced diabetic rats treated with acarbose. [Journal Article]
- MBMetab Brain Dis 2018 Feb 12
- There are strong correlations between diabetes mellitus and cognitive dysfunction. This study sought to investigate the modulatory effects of Moringa oleifera leaf (ML) and seed (MS) inclusive diets ...
There are strong correlations between diabetes mellitus and cognitive dysfunction. This study sought to investigate the modulatory effects of Moringa oleifera leaf (ML) and seed (MS) inclusive diets on biomolecules [acetylcholinesterase (AChE), butyrylcholinesterase (BChE)] angiotensin-I converting enzyme (ACE), arginase, catalase, glutathione transferase (GST) and glutathione peroxidase (GSH-Px) activities, glutathione (GSH) and nitric oxide (NO) levels] associated with cognitive function in the brain of streptozotocin (STZ)-induced diabetic rats treated with acarbose (ACA). The rats were made diabetic by intraperitoneal administration of 0.1 M sodium-citrate buffer (pH 4.5) containing STZ [60 mg/kg b.w (BW)] and fed with diets containing 2 and 4% ML/MS. Acarbose (25 mg/kg BW) was administered by gavage daily for 14 days. The animals were distributed in eleven groups of eight animals as follows: control, STZ-induced, STZ + ACA, STZ + 2% ML, STZ + ACA + 2% ML, STZ + 4% ML, STZ + ACA + 4% ML, STZ + 2% MS, STZ + ACA + 2% MS, STZ + 4% MS, STZ + ACA + 4% MS. There were marked increase in AChE, BChE, arginase, ACE and concomitant decrease in catalase, GST, GSH-Px, activities and NO levels in STZ-diabetic group compared with the control. However, there was a decrease in AChE, BChE and ACE activities and concomitant increase in the antioxidant molecules in the groups fed with supplemented diets treated with/without ACA compared with the STZ-diabetic group. These findings suggest that ML/MS supplemented diet could prevent cognitive dysfunction-induced by chronic hyperglycemia.
- Inhibitory activity of phenolic-rich pistachio green hull extract-enriched pasta on key type 2 diabetes relevant enzymes and glycemic index. [Journal Article]
- FRFood Res Int 2018; 105:94-101
- Phenolic compounds as agro-industrial by-products have been associated with health benefits since they exhibit high antioxidant activity and anti-diabetic properties. In this study, polyphenol-rich e...
Phenolic compounds as agro-industrial by-products have been associated with health benefits since they exhibit high antioxidant activity and anti-diabetic properties. In this study, polyphenol-rich extract from pistachio green hull (PGH) was evaluated for antioxidant activity and its ability to inhibit α-amylase and α-glucosidase activity in vitro. The effect of PGH extract powder on in vitro starch digestibility was also evaluated. The results showed that PGH had stronger antioxidant activity than Trolox. The inhibitory effect of PGH extract against α-amylase from porcine pancreas was dose dependent and the IC50value was ~174μgGAE/mL. The crude PGH extract was eight times more potent on baker yeast α-glucosidase activity (IC50~6μgGAE/mL) when compared to acarbose, whereas the IC50value of PGH extract against rat intestinal maltase activity obtained ~2.6mgGAE/mL. The non-tannin fraction of PGH extract was more effective against α-glucosidase than tannin fraction whereas the α-amylase inhibitor was concentrated in the tannin fraction. In vitro starch digestibility and glycemic index (GI) of pasta sample supplemented with PGH extract powder (1.5%) was significantly lower than the control pasta. The IC50value of PGH extract obtained from cooked pasta against α-amylase and α-glucosidase was increased. These results have important implications for the processing of PGH for food industry application and therefore could comply with glucose control diets.
- Acarbose inhibits the proliferation and migration of vascular smooth muscle cells via targeting Ras signaling. [Journal Article]
- VPVascul Pharmacol 2018 Feb 09
- Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are importan...
Atherosclerosis involves the proliferation and migration of vascular smooth muscle cells (VSMCs). The migration of VSMCs from the media into the intima and their subsequent proliferation are important processes in neointima formation in atherosclerosis and restenosis after percutaneous coronary interventions. Acarbose, an alpha-glucosidase inhibitor, has been demonstrated to not affect serum levels of glucose and decrease the progression of intima-media thickening in rabbits fed with a high cholesterol diet (HCD). We previously showed that increased Ras protein levels enhanced the migration of TNF-α treated A7r5 cells. The aim of this study was to determine the inhibitory effects of acarbose on Ras expression in A7r5 cells. Acarbose also inhibited the phosphorylation of focal adhesion kinase (FAK) and Akt, activities of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9, and protein expressions of small G proteins (Ras, Cdc42, RhoA, and Rac1) in a dose-dependent manner. We also found that acarbose could effectively inhibit the proliferation and migration of RasG12VA7r5 cells by blocking small G proteins and phosphoinositide-3-kinase (PI3K)/Akt signaling. These studies demonstrated that acarbose could theoretically decrease atherosclerosis by targeting Ras signaling.
- Oroxin A from Oroxylum indicum prevents the progression from prediabetes to diabetes in streptozotocin and high-fat diet induced mice. [Journal Article]
- PPhytomedicine 2018 Jan 01; 38:24-34
- CONCLUSIONS: Oroxin A prevents the progression from prediabetes to diabetes through a multi-pathway intervention mechanism.
- Combinatorial Peptide Library Screening for Discovery of Diverse α-glucosidase Inhibitors Using Molecular Dynamics Simulations and Binary QSAR Models. [Journal Article]
- JBJ Biomol Struct Dyn 2018 Feb 08; :1-18
- Human α-glucosidase is an enzyme involved in the catalytic cleavage of the glucoside bond and involved in numerous functionalities of the organism, as well as in the insurgence of diabetes mellitus 2...
Human α-glucosidase is an enzyme involved in the catalytic cleavage of the glucoside bond and involved in numerous functionalities of the organism, as well as in the insurgence of diabetes mellitus 2 and obesity. Thus, developing chemicals that inhibit this enzyme is a promising approach for the treatment of several pathologies. Small peptides such as di- and tri-peptides may be in natural organism as well as in the GI tract in high concentration, coming from the digestive process of meat, wheat and milk proteins. In this work, we reported the first tentative hierarchical structure-based virtual screening of peptides for human α-glucosidase. The goal of this work is to discover novel and diverse lead compounds that my act as inhibitors of α-glucosidase such as small peptides by performing a computer aided virtual screening and to find novel scaffolds for further development. Thus, in order to select novel candidates with original structure we performed molecular dynamics (MD) simulations among the 12 top-ranked peptides taking as comparison the MD simulations performed on crystallographic inhibitor acarbose. The compounds with the lower RMSD variability during the MD, were reserved for in vitro biological assay. The selected 4 promising structures were prepared on solid phase peptide synthesis and used for the inhibitory assay, among them compound 2 showed good inhibitory activity, which validated our method as an original strategy to discover novel peptide inhibitors. Moreover, pharmacokinetic profile predictions of these 4 peptides were also carried out with binary QSAR models using MetaCore/MetaDrug applications.
- Design, synthesis and in vitro α-glucosidase inhibition of novel dihydropyrano[3,2-c]quinoline derivatives as potential anti-diabetic agents. [Journal Article]
- BCBioorg Chem 2018 Feb 02; 77:280-286
- A novel series of dihydropyrano[3,2-c]quinoline derivatives 6a-q were synthesized and evaluated for their in vitro α-glucosidase inhibitory activities. All newly synthesized compounds displayed poten...
A novel series of dihydropyrano[3,2-c]quinoline derivatives 6a-q were synthesized and evaluated for their in vitro α-glucosidase inhibitory activities. All newly synthesized compounds displayed potent α-glucosidase inhibitory activity in the range of 10.3 ± 0.3 µM-172.5 ± 0.8 µM against the yeast α-glucosidase enzyme when compared to the standard drug acarbose (IC50 = 750.0 ± 1.5 µM). Among these compounds, compounds 6e and 6d displayed the most potent α-glucosidase inhibitory activity (IC50 = 10.3 ± 0.3 and 15.7 ± 0.5 µM, respectively). The kinetic analysis of the most potent compounds 6e and 6d revealed that compound 6e inhibited α-glucosidase in an uncompetitive manner (Ki = 11 µM) while compound 6d was a non-competitive inhibitor (Ki = 28 µM) of the enzyme. Then, the cytotoxicity of the most potent compounds (i.e., compounds 6a, 6d, 6e, 6 g, 6j, and 6l) were evaluated for toxicity using the breast cancer cell lines MDA-MB231, MCF-7, and T-47D by using a MTT assay, and no toxicity was observed.
- A new entry into the portfolio of α-glucosidase inhibitors as potent therapeutics for type 2 diabetes: Design, bioevaluation and one-pot multi-component synthesis of diamine-bridged coumarinyl oxadiazole conjugates. [Journal Article]
- BCBioorg Chem 2018 Jan 16; 77:190-202
- Diabetes mellitus (DM), a chronic multifarious metabolic disorder resulting from impaired glucose homeostasis has become one of the most challenging diseases with severe life threat to public health....
Diabetes mellitus (DM), a chronic multifarious metabolic disorder resulting from impaired glucose homeostasis has become one of the most challenging diseases with severe life threat to public health. The inhibition of α-glucosidase, a key carbohydrate hydrolyzing enzyme, could serve as one of the effective methodology in both preventing and treating diabetes through controlling the postprandial glucose levels and suppressing postprandial hyperglycemia. In this context, three series of diamine-bridged bis-coumarinyl oxadiazole conjugates were designed and synthesized by one-pot multi-component methodology. The synthesized conjugates (4a-j, 5a-j, 6a-j) were evaluated as potential inhibitors of glucosidases. Compound 6f containing 4,4'-oxydianiline linker was identified as the lead and selective inhibitor of α-glucosidase enzyme with an IC50value of 0.07 ± 0.001 μM (acarbose: IC50 = 38.2 ± 0.12 μM). This inhibition efficacy was ∼545-fold higher compared to the standard drug. Compound 6f was also emerged as the lead molecule against intestinal maltase-glucoamylase with good inhibition strength (IC50 = 0.04 ± 0.02 μM) compared to acarbose (IC50 = 0.06 ± 0.01 μM). Against β-glucosidase enzyme, compound 6 g was noted as the lead inhibitor with IC50value of 0.08 ± 0.002 μM. Michaelis-Menten kinetic experiments were performed to explore the mechanism of inhibition. Molecular docking studies of the synthesized library of hybrid structures against glucosidase enzyme were performed to describe ligand-protein interactions at molecular level that provided an insight into the biological properties of the analyzed compounds. The results suggested that the inhibitors could be stabilized in the active site through the formation of multiple interactions with catalytic residues in a cooperative fashion. In addition, strong binding interactions of the compounds with the amino acid residues were effective for the successful identification of α-glucosidase inhibitors.
New Search Next
- Morning glory resin glycosides as α-glucosidase inhibitors: In vitro and in silico analysis. [Journal Article]
- PPhytochemistry 2018 Feb 01; 148:39-47
- Twenty-seven individual resin glycosides from the morning glory family (Convolvulaceae) were evaluated for their α-glucosidase inhibitory potential. Four of these compounds displayed an inhibitory ac...
Twenty-seven individual resin glycosides from the morning glory family (Convolvulaceae) were evaluated for their α-glucosidase inhibitory potential. Four of these compounds displayed an inhibitory activity comparable to acarbose, which was used as a positive control. Molecular modeling studies performed by docking analysis were accomplished to predict that the active compounds and acarbose bind to the α-1,4-glucosidase enzyme catalytic site of MAL12 from the yeast Saccharomyces cerevisiae through stable hydrogen bonds primarily with the amino acid residues HIS279 and GLN322. Docking studies with the human maltase-glucoamylase (MGAM) also identified binding modes for resin glycosides inside the catalytic site in the proximity of TYR1251. These results postulate that resin glycosides may be a source of phytotherapeutic agents with antihyperglycemic properties for the prophylaxis and treatment of non-insulin-dependent type 2 diabetes mellitus.