Natural Flavonoids And Anthocyanins In Blueberry-blackberry Wine For Dipeptidyl Peptidase ? (DPP-?) Inhibitory Activity

Beneficial health effects of fruits and vegetables in the diet have been attributed to their high flavonoid content.Dipeptidyl peptidase ?(DPP-?)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-? by using a luminescence assay and computational modeling.1)ANC from blueberry-blackberry wine(BBW)blends strongly inhibited DPP-? activity(IC50,0.07±0.02 to>300 ?M).Malvidin-3-galactoside,cyanidin-3-glucoside and delphinidin-3-arabinoside were the main ANC present in the blueberry-blackberry wine.2)Of the twenty-seven phenolics tested,the most potent DPP-? 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.3)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-?.These results indicate that flavonoids,particularly luteolin,apigenin,and flavone,and the stilbenoid resveratrol can act as naturally occurring DPP-? inhibitors.