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

SIMPLE SUMMARY: The chemical investigation of Chrozophora oblongifolia aerial parts resulted in the isolation of five phenolic compounds. The isolated metabolites were tested for their antioxidant and advanced glycation end-products (AGEs) formation, α-glucosidase, and lipase inhibitory activities. 1,3,6-Trigalloyl glucose exhibited the highest activity as an antioxidant and AGEs inhibitor as well as an α-glucosidase inhibitor. It showed promising binding affinity and stability towards the human intestinal maltase-glucoamylase α-glucosidases, as revealed through coupled molecular docking and dynamics studies that could encourage the utilization of this compound in the management of diabetes and its complications. 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.