Phenolic Extracts from Extra Virgin Olive Oils Inhibit Dipeptidyl Peptidase IV Activity: In Vitro, Cellular, and In Silico Molecular Modeling Investigations

Two extra virgin olive oil (EVOO) phenolic extracts (BUO and OMN) modulate DPP-IV activity. The in vitro DPP-IV activity assay was performed at the concentrations of 1, 10, 100, 500, and 1000 μg/mL, showing a dose-dependent inhibition by 6.8 ± 1.9, 17.4 ± 6.1, 37.9 ± 2.4, 57.8 ± 2.9, and 81 ± 1.4% for BUO and by 5.4 ± 1.7, 8.9 ± 0.4, 28.4 ± 7.2, 52 ± 1.3, and 77.5 ± 3.5% for OMN. Moreover, both BUO and OMN reduced the DPP-IV activity expressed by Caco-2 cells by 2.9 ± 0.7, 44.4±0.7,61.2±1.8,and85±4.2%andby3±1.9,35±9.4,60±7.2,and82±2.8%,respectively,at the same doses. The concentration of the most abundant and representative secoiridoids within both extracts was analyzed by nuclear magnetic resonance (1H-NMR). Oleuropein, oleacein, oleocanthal, hydroxytyrosol, and tyrosol, tested alone, reduced the DPP-IV activity, with IC50 of 472.3 ± 21.7, 187 ± 11.4, 354.5 ± 12.7, 741.6 ± 35.7, and 1112 ± 55.6 μM, respectively. Finally, in silico molecular docking simulations permitted the study of the binding mode of these compounds.