Metabolomics and cheminformatics bioprospection of corn silk against key enzymes implicated in type 2 diabetes mellitus and its complications

Abstract

The rising prevalence of type 2 diabetes mellitus (T2DM) and the side effects of synthetic hypoglycemic agents underscore the need for new antidiabetic compounds. Corn silk (CS) is known for its antidiabetic properties, but its mechanism remains unclear. This study explored the potential of CS constituents in modulating six key enzymes linked to T2DM and its complications: alpha-amylase (AA), alpha-glucosidase (AG), aldose reductase (AR), dipeptidyl peptidase-4 (DPP-4), protein tyrosine phosphatase 1B (PTP1B), and sorbitol dehydrogenase (SDH), using computational techniques. Ultra-performance liquid chromatography-mass spectrometry identified 128 metabolites across three CS extracts (aqueous, hydro-ethanol, and ethanol) from premature and mature developmental stages. Mature CS had a higher metabolite abundance, particularly in the hydro-ethanolic extract. An insight into the structural interaction and binding energy calculations over a 120-ns molecular dynamics simulation identified R-7-butyl-6,8-dihydroxy-3-[(3E)-pent-3-en-1-yl]-3,4-dihydroisochromen-1-one (−40.30 kcal/mol), 1-O-vanilloyl-beta-D-glucose (−34.17 kcal/mol), (-)-11-hydroxy-9,10-dihydrojasmonic acid 11-beta-D-glucoside (−44.13 kcal/mol), p-coumaroyl malic acid (−34.40 kcal/mol), 2-hydroxydecanedioic acid (−19.71 kcal/mol), and (-)-11-hydroxy-9,10-dihydrojasmonic acid 11-beta-D-glucoside (−36.61 kcal/mol) with the highest negative binding free energy against AA, AG, AR, DPP-4, PTP1B, and SDH, respectively. Post-MD simulation confirmed the formation of more thermodynamically stable CS metabolites-enzyme complexes in comparison to the respective reference standard-enzyme complexes. Evidence from this study shows that CS metabolites possess potential inhibitory effects on the investigated targets and suggest that CS and its metabolites could be a potential alternative for managing T2DM.