Berry and citrus henolic compounds inhibit dipeptidyl peptidase IV, implications in diabetes management

Full Title: Berry and citrus henolic compounds inhibit dipeptidyl peptidase IV, implications in diabetes management

Journal: Evidence-Based Complementary and Alternative Medicine

Year of Publication: 2013

PHHI Author(s): Mary Ann Lila
Publication Author(s): Fan, Junfeng, Michelle Johnson, Mary Ann Lila, Gad Youself, and Elvira Gonzalez de Mejia

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  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.

Link to Article: http://www.hindawi.com/journals/ecam/2013/479505/