Barosmin against postprandial hyperglycemia: outputs from computational prediction to functional responses in vitro

Previously, barosmin has been demonstrated to possess anti-diabetic action. However, its effect to inhibit alpha-amylase and alpha-glucosidase, including glucose utilization efficacy, has yet to be revealed. Hence, the current study attempted to assess the efficiency of barosmin in inhibiting the alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase 4 enzymes, including glucose uptake efficacy. Molecular docking and simulation were performed using AutoDock Vina and Gromacs respectively followed by gene ontology analysis using the database for annotation, visualization, and integrated discovery. Further, in vitro enzyme inhibitory activities and glucose uptake assay were performed in L6 cell lines. Density functional theory analysis detailed mechanistic insights into the crucial interaction sites of barosmin of which the electron-dense region was prone to nucleophilic attack (O-atoms) whereas hydroxyl groups (-OH) showed affinity for electrophilic attacks. Barosmin showed good binding affinity with alpha-amylase (-9.2kcal/mol), alpha-glucosidase (-10.7kcal/mol), and dipeptidyl peptidase 4 (-10.0kcal/mol). Barosmin formed stable nonbonded contacts with active site residues of aforementioned enzymes throughout 200ns molecular dynamics simulation. Further, it regulated pathway concerned with glucose homeostasis i.e. tumor necrosis factor signaling pathway. In addition, barosmin showed alpha-amylase (IC50= 95.77 +/- 23.33 mu g/mL), alpha-glucosidase (IC50= 68.13 +/- 2.95 mu g/mL), and dipeptidyl peptidase 4 (IC50= 13.27 +/- 1.99 mu g/mL) inhibitory activities including glucose uptake efficacy in L6 cell lines (EC50= 12.46 +/- 0.90 mu g/mL) in the presence of insulin. This study presents the efficacy of the barosmin to inhibit alpha-amylase and alpha-glucosidase and glucose uptake efficacy in L6 cell lines via the use of multiple system biology tools and in vitro techniques. [GRAPHICS] .