Berry and Citrus Phenolic Compounds Inhibit Dipeptidyl Peptidase IV: Implications in Diabetes Management.

ABSTRACT: Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content. Dipeptidyl peptidase IV (DPP-IV) is a serine aminopeptidase that is a novel target for type 2 diabetes therapy due to its incretin hormone regulatory effects. In this study, well-characterized anthocyanins (ANC) isolated from berry wine blends and twenty-seven other phenolic compounds commonly present in citrus, berry, grape, and soybean, were individually investigated for their inhibitory effects on DPP-IV by using a luminescence assay and computational modeling. ANC from blueberry-blackberry wine blends strongly inhibited DPP-IV activity (IC50, 0.07?±?0.02 to >300? ? M). Of the twenty-seven phenolics tested, the most potent DPP-IV inhibitors were resveratrol (IC50, 0.6?±?0.4?nM), luteolin (0.12?±?0.01? ? M), apigenin (0.14?±?0.02? ? M), and flavone (0.17?±?0.01? ? M), with IC50 values lower than diprotin A (4.21?±?2.01? ? M), a reference standard inhibitory compound. Analyses of computational modeling showed that resveratrol and flavone were competitive inhibitors which could dock directly into all three active sites of DPP-IV, while luteolin and apigenin docked in a noncompetitive manner. Hydrogen bonding was the main binding mode of all tested phenolic compounds with DPP-IV. These results indicate that flavonoids, particularly luteolin, apigenin, and flavone, and the stilbenoid resveratrol can act as naturally occurring DPP-IV inhibitors.

SUBMITTER: Fan J 

PROVIDER: S-EPMC3773436 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature