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

2013; Hindawi Publishing Corporation; Volume: 2013; Linguagem: Inglês

10.1155/2013/479505

1741-4288

Junfeng Fan, Michele H. Johnson, Mary Ann Lila, Gad G. Yousef, Elvira González de Mejı́a,

Pineapple and bromelain studies

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 μ 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 μ M), apigenin (0.14 ± 0.02 μ M), and flavone (0.17 ± 0.01 μ M), with IC50 values lower than diprotin A (4.21 ± 2.01 μ 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.