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Evidence-Based Complementary and Alternative Medicine
Volume 2013 (2013), Article ID 479505, 13 pages
Research Article

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

1College of Bioscience and Biotechnology, Beijing Forestry University, Beijing 100083, China
2Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
3Plants for Human Health Institute, NC Research Campus, North Carolina State University, Kannapolis, NC 28081, USA
4Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Drive, Urbana, IL 61801, USA

Received 30 March 2013; Revised 1 July 2013; Accepted 1 July 2013

Academic Editor: Mohd Roslan Sulaiman

Copyright © 2013 Junfeng Fan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.