In silico Assessment of Dipeptidyl Peptidase 4 (DPP-4) Inhibiting Potential of a few Bioactive Compounds Present in Black Rice Bran for Effective Management of Postprandial Hyperglycemia

Abstract

Abstract Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of prescription medicines that are used to control hyperglycemia in adults with type 2 diabetes. DPP-4 inhibitors lower blood sugar by helping the body increase the level of the hormone insulin after meals. In recent years many phenolic compounds, isolated from folk medicinal plants with anti- diabetic activity, are proved to show potent inhibitory effects against DPP- 4 enzyme. Black rice bran extract, which is rich in phenols, produces hyperglycemic effect on experimental animals. The present study was designed to evaluate molecular interactions existing between the major bioactive compounds present in black rice bran and DPP-4 enzyme. Molecular docking, binding energy calculation, evaluation of ADMET properties and Molecular Dynamics simulation for 50 nanoseconds were carried out to reveal the nature and stability of the enzyme-ligand complex formed due to such interactions. The results obtained indicate that out of the six bioactive compounds chosen, C3G (cyanidin 3-O-glucoside) and FLS (6´-O-feruloylsucrose) have the highest docking scores and they can produce stable complexes with DPP-4 which might lead to its inactivation. Therefore, it can be concluded that black rice bran extract may produce antidiabetic activity by inhibiting the DPP-4 enzyme. Moreover, the pharmacokinetic studies reveal that the compounds chosen are safe and produce no hepatotoxicity. This preliminary theoretical study can provide a strong base for further studies towards the development of lead molecules for new antidiabetic drugs with lower side effects.