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

Competitive inhibition of phytic acid on enzymatic browning of chestnut (Castanea mollissima Blume)

“…To validate the crystal structure of the ligand, the docking was carried out in 100 genetic algorithm runs, and the remaining genetic algorithm parameters were maintained at their default values. The optimal docking results were obtained when the lowest binding energy (∆G) in the conformation was reached by using the following equation (FAN et al, 2013):…”

Antioxidant, Antimicrobial, and Antidiabetic Activities of Crowberry Fruits

“…Therefore, Gram-negative bacteria are resistant to the extract of crowberry fruit. Epidemiological studies have suggested that edible berries are beneficial in reducing the risk of type-2 diabetes [27,28] . To identify the potential of crowberry fruit as an antidiabetic supplement, crude 70 % ethyl alcohol extract and its fractions were tested for α-glucosidase and α-amylase inhibitory activities.…”

Identification and characterization of a dipeptidyl peptidase IV inhibitor from aronia juice

“…Cyanidin 3, 5-diglucoside in aronia juice fraction was found as the main component to act as a DPP IV inhibitor. It has been reported that phenolic compounds such as cyanidin, cyanidin-3-glucocide, malvidin, luteolin, apigenin, quercetin, kaempferol, hesperetin, naringenin, eriocitrin, genistein, resveratrol, gallic acid and caffeic acid are DPP IV inhibitors in berries and citrus fruit [17]. In food protein hydrolysates, DPP IV inhibitors have been reported to be derivative peptides from atlantic salmon skin, tuna cooking juice, Japanese rice bran, gouda cheese and milk protein [18].…”

“…Previous studies have also shown that aronia juice contains anthocyanin glycosides including cyanidin 3-galactoside, cyanidin 3-arabinoside, cyanidin 3-gulcoside and cyanidin 3-xyloside [19][20][21][22][23][24]. Furthermore, cyanidin and cyanidin 3-glucoside have been reported to be DPP IV inhibitors [17]. We found that DPP IV activity was inhibited more strongly by cyanidin 3, 5-diglucoside than by cyanidin and cyanidin 3-glucoside, which have been reported to be DPP IV inhibitors.…”