Impact of some bioactive compounds of flavonoid-rich fraction of Monodora tenuifolia, Benth on glucose concentration and certain proteins associated with glucose metabolism using molecular docking approach

Abstract

Hyperglycemia is a hallmark of diabetes mellitus, known to be a metabolic disorder caused by excess blood glucose due to lack of insulin secretion, or cellular insensitivity to insulin or damage to pancreatic β-cell. This study focused on the potential of flavonoid-rich fraction of M. tenuifolia seeds (FRFMTS) to reducing plasma glucose concentration in diabetic rats and determine the molecular interaction of some phytochemicals in FRRMTS against certain proteins associated with diabetes mellitus. The plant sample was pulverized and extracted at 1g in 5 ml of 80% v/v ethanol to obtain hydro-ethanol extract subjected to solvent-solvent fractionation to obtain the FRFMTS used for HPLC screening. Seven (7) groups of male Wistar rats containing six (6) rats each were used. The groups were normal control, 25 mg/kg FRFMTS, 50 mg/kg FRFMTS, diabetic control, diabetic rats + 25 mg/kg FRFMTS, diabetic rats + 50 mg/kg FRFMTS and diabetic rats + metformin (6.67 mg/kg). A glucose oxidase kit was used to determine blood glucose concentrations, while the molecular interactions with some target proteins were docked using the extra precision (XP) algorithm. The results revealed a significant increase in the plasma glucose of diabetic control group in comparison to normal control group. Diabetic rats treated with 25 mg/kg FRFMTS, 50 mg/kg FRFMTS and metformin showed that glucose concentrations significantly reduced compared to diabetic control group. The molecular docking model revealed highest binding affinity of quercetin to acetyl-CoA carboxylase, glucose-1-transporter, glycogen synthase kinase 3β, glucagon-like peptide 1 and insulin receptor kinase. This study suggests that FRFMTS possesses glucose lowering ability and quercetin present in FRFMTS binds effectively to proteins linked to diabetes and could elicit antihyperglycemic effect.