DPP-IV Inhibitory Potentials of Flavonol Glycosides Isolated from the Seeds of Lens culinaris: In Vitro and Molecular Docking Analyses.

Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2 diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the inactivation of GLP-1, permitting the incretin to stimulate insulin release, thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors from medicinal plants and foods, three flavonol glycosides (<bold>1</bold>–<bold>3</bold>) were isolated from the seeds of <italic>Lens culinaris</italic> Medikus (Fabaceae) and tested for their DPP-IV–inhibitory activity. We demonstrated for the first time, that compounds <bold>1</bold>–<bold>3</bold> inhibited DPP-IV activity in a concentration-dependent manner in our in vitro bioassay system. In addition, molecular docking experiments of compounds <bold>1</bold>–<bold>3</bold> within the binding pocket of DPP-IV were conducted. All investigated compounds readily fit within the active sites of DPP-IV, in low-energy conformations characterized by the flavone core structure having optimal electrostatic attractive interactions with the catalytic triad residues of DPP-IV. [ABSTRACT FROM AUTHOR]