α-Glucosidase inhibitors from brown rice bound phenolics extracts (BRBPE): Identification and mechanism

Abstract

Brown rice bound phenolics extracts (BRBPE) have been reported to possess α-glucosidase inhibitory effects, the specific enzyme inhibitors involved in this process were unknown. Here, α-glucosidase inhibitors in BRBPE were screened using bioaffinity ultrafiltration methods, and seven phenolic compounds - three monomers (p-coumaric acid, ferulic acid and methyl ferulate), three dimers (8-5', 5-5' and 8-O-4' diferulic acid) and a trimer (5-5'/8-O-4″ dehydrotriferulic acid) were identified as exact inhibitors, among which 5-5'/8-O-4″ dehydrotriferulic acid and 5-5'diferulic acid exhibited the best inhibitory activity. Enzyme kinetic analysis suggested that the inhibitory mechanism of these seven inhibitors including competitive, noncompetitive, uncompetitive and mixed manner. Molecular docking analysis revealed that the seven inhibitors bind with α-glucosidase mainly by hydrogen bonding interaction, hydrophobic force and ionic bond. Molecular dynamics simulation further explored the structure and molecular property of phenolic-glucosidase complex. This work provided a deep insight into brown rice bound phenolics acting as potent α-glucosidase inhibitors.

Keywords: 5-5′ Diferulic acid (PubChem CID 5281770); 5-5′/8-O-4″ Dehydrotriferulic acid (PubChem CID 71578617); 8-5′ Diferulic acid (PubChem CID10385447); 8-O-4′ Diferulic acid (PubChem CID 10249540); Acarbose (PubChem CID 41774); Bound phenolics; Brown rice; Ferulic acid (PubChem CID445858); Inhibitory kinetics; Methyl ferulate (PubChem CID5357283); Molecular simulation; Ultrafiltration; p-Coumaric acid (PubChem CID637542); α-Glucosidase inhibitory activity.