Diabetes is a chronic metabolic disorder marked by postprandial hyperglycemia due to several etiologies including abnormal carbohydrate digestion and glycation of hemoglobin. The prolong use of synthetic drugs results in characteristic side effects which necessitates the discovery of safe and cost-effective substitutes. The aim of the current study is to isolate and evaluate the antidiabetic potential of the phenolic compounds from the leaves of Tradescantia pallida. Syringic acid, p-coumaric acid, morin and catechin (compounds 1-4) were isolated and characterized from Tradescantia pallida leaves using column chromatography and spectroscopic techniques. The in vitro antidiabetic potential of the phenolic compounds were assessed using α-amylase and non-enzymatic glycosylation of hemoglobin protein assays. A mechanistic insight of interactions between phenolic compounds and human α-amylase and hemoglobin protein were scrutinized by employing molecular docking method. Prime Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) calculations were carried out to find the binding energies of the ligand-protein complexes. Morin and catechin were further analyzed to find the dynamic and thermodynamic constraints of the complexes under specific biological conditions using molecular dynamic simulation trajectories. The stability and flexibility of the complexes were justified by fluctuation of α-carbon chain, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF) and type of interactions involved which authenticated the in vitro inhibitory potential of morin and catechin against enzymatic and non-enzymatic pathways. The current study could be fruitful in rational designing of safe antidiabetic drugs of natural origin.Communicated by Ramaswamy H. Sarma.
Keywords: MD simulation; MM-GBSA; Phenols; Tradescantia pallida; hemoglobin; medicinal plant; molecular docking; phenolic compounds; α-amylase.