Phenolics from Chrozophora oblongifolia Aerial Parts as Inhibitors of α-Glucosidases and Advanced Glycation End Products: In-Vitro Assessment, Molecular Docking and Dynamics Studies

Abstract

Modern life is associated with low physical activity that leads to the accumulation of fats, gaining more weight, and obesity. Accumulation of fat in the abdomen region contributes to diabetes via insulin resistance and hyperglycemia. Polyphenols are major plant constituents that exert antidiabetic activity through different mechanisms, including radicle scavenging activity, regulation of glucose uptake, and inhibition of fat and polysaccharide hydrolysis in addition to their inhibitory role regarding the formation of advanced glycation end products (AGEs). Chemical investigation of C. oblongifolia aerial parts resulted in the isolation of five major compounds: apeginin-7-O-β-D-glucoside (1), quercetin-3-O-β-D-glucuronic acid (2), quercetin-3-O-β-D-galacturonic acid (3), rutin (4), and 1,3,6-trigalloyl glucose (5). The isolated compounds were tested for their antioxidant and AGEs formation, α-glucosidase, and lipase inhibitory activities. Compound 5 revealed the highest antioxidant and AGEs inhibitory activity in bovine serum albumin (BSA)-methylglyoxal, BSA-fructose, and arginine-methylglyoxal models. Moreover, it exhibited a potent inhibitory profile on Saccharomyces cerevisiae α-glucosidases compared to the positive control, acarbose. Compound (5) further depicted promising binding affinity and stability towards the human intestinal maltase-glucoamylase α-glucosidases, which is a diabetes-related therapeutic target, through coupled molecular docking and dynamics studies. The obtained results encourage the usage of 1,3,6-trigalloyl glucose in the management of diabetes and its complications. However, detailed in-vivo studies for this compound should be performed.

Deciphering Molecular Aspects of Potential α-Glucosidase Inhibitors within Aspergillus terreus: A Computational Odyssey of Molecular Docking-Coupled Dynamics Simulations and Pharmacokinetic Profiling

“…Several of these polar residues were of higher negative values in systems of the top-docked hits, as well as the acarbose reference ligand. The depicted ligand–residue pattern was in good agreement with reported molecular dynamics studies for both nature-isolated and synthesized compounds [ 36 , 97 , 98 , 99 , 102 ]. On the other hand, the energy contributions of several hydrophobic pocket residues, such as Trp299, Ile328, Ile364, Val405, Trp406, Trp441, Val447, Trp539, and Phe575, were only significant for the aromatic/hydrophobic hits (up to −10.27 kJ/mol for Trp406).…”

“…Increased polar solvation energy for acarbose could be the reason for oxygen functionalities. Despite being important for furnishing polar contact with -1 and +1 sugar subsites, they can act as double blades increasing solvation entropy since the target pocket is shallow and solvent-exposed [ 7 , 36 ]. On the other hand, increased ligand hydrophobicity for SK-132 and SK-58, particularly through aromatic scaffolds, could rationalize a significant solvation penalty.…”

“…Setting the binding site for docking was guided by the information obtained from the co-crystallized ligand bounded to the hi MGAG target protein. A grid docking box was created to accommodate all essential amino acids being viewed at the deposited complex file, as well as those being reported as crucial for the anchoring of small molecule ligands [ 28 , 34 , 35 , 36 ]. Using the grid generation tool within AutoDock, a grid box was constructed at the center atom of the co-crystallized ligand, with an external size of 80 Å × 80 Å × 80 Å and 0.38 Å grid-point spacing along the XYZ-cartesian coordinates.…”

Antioxidant, antidiabetic and anticancer effects of persimmon leave extracts in vitro

“…The assay was carried out according to the method of (Abdallah et al, 2022), briefly, in 96microwell plates, 25 μL of samples/blank were incubated for 10 min at 37C with 50 μL of αglucosidase from Saccharomyces cerevisiae (0.6 U / mL) in phosphate buffer (0.1 M, pH 7). Then, 25 μL of 3 mM pNPG as a substrate in phosphate buffer (pH 7) was added, and the mixture was incubated again for 5 min at 37°C.…”

α-Glucosidase, butyrylcholinesterase and acetylcholinesterase inhibitory activities of phenolic compounds from Carthamus tinctorius L. flowers: In silico and in vitro studies

“…This leads to hyperglycemia after meals and can result in ketoacidosis and protein loss ( Abdallah et al, 2011 , Abdallah et al, 2016 ). A method for treating diabetes involves blocking the conversion of complex carbohydrates into simple sugars by inhibiting the enzymes α-glucosidase and α-amylase ( Abdallah et al, 2022 , Omar et al, 2022 ). Miglitol and acarbose, two commonly used α-glucosidase inhibitors, are associated with a range of side effects such as renal tumors, liver damage, abdominal discomfort, diarrhea, and gas.…”