Anti-Diabetic Potential of Anti-Oxidant Compounds "Riboflavin, Flavin Mononucleotide and Flavin Adenine Dinucleotide" with High Therapeutic Potency through Inhibition of α-Amylase and α-Glucosidase Enzymes at Sub-Micromolar Concentrations

Abstract

Diabetes is a group of metabolic disorders characterized by a high blood sugar level over a prolonged period of time. Inhibition of carbohydrate hydrolyzing enzymes leads to decrease in the absorption of glucose which is considered as one of the effective managements of diabetes mellitus. Vegetable, fruit, milk, and fish are good sources of riboflavin (RF) and vitamin B5 with versatile health benefits. The well-adapted structural features of these compounds for the inhibition/activation of enzymes include several available hydrogen bond (H-bond) acceptors and donors, flexible backbone, and hydrophobic nature. The substrates of α-amylase (α-Amy) and α-glucosidase (α-Glu), known as key absorbing enzymes, have functional groups (OH groups) resembling RF and vitamin B5. Therefore, the present study was conducted to evaluate the inhibitory properties of fliavin, RF, flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) and vitamin B5 against α-Amy and α-Glu. The median inhibition concentration (IC50) values for α-Glu in the presence of RF, FMN and FAD were determined 136.7±4.8, 235.4±5.2 and 78.9±3.4, respectively. The IC50 values α-Amy in the presence of RF, FMN and FAD were determined 165.6±7.1, 253.6±5.5 and 131.2±6.3, respectively. Moreover, the Ki values of RF were calculated as 14.2±1.8 and 18.6±1.7 µM for α-Glu and α-Amy in a mixed-mode. In addition, to communicate with the active site of α-Glu and α-Amy respectively, RF presented a binding energy of -8.1 and -7.3 kcal/mol, FMN -7.1 and -6.8, and FAD -10.3 and -7.8 kcal/mol. These antioxidant inhibitors may be potential anti-diabetic drugs, not only to reduce glycemic index, but also to limit the activity of the major reactive oxygen species (ROS) producing pathways. Key words: Riboflavin, hydrolyzing enzymes, enzyme inhibition, hyperglycemia Introduction