Citrus bioflavonoids dipeptidyl peptidase-4 inhibition compared with gliptin antidiabetic medications

摘要

This study compared dipeptidyl peptidase-4 (DPP-4) inhibitory activity of citrus bioflavonoid nutra-ceuticals compared with three gliptins. Citrus bioflavonoid standards and three commercially available citrus bioflavonoid supplements (Thompson's Super Bioflavonoid Complex (R)(SB), Ethical Nutrients Bioflavonoids Plus Vitamin C (R)(EN), and Country Life Citrus Bioflavonoids and Rutin (R)(CB)) were considered in this study. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis was undertaken to identify and quantitate the citrus bioflavonoids present in each supplement. The DPP-4 inhibitory activity was determined by fluorometric assay. All of the tested individual citrus flavonoids demonstrated DPP-4 inhibitory activity, with IC50 values ranging from 485 mu M (rutin) to 5700 mu M (hesperitin and eriodictyol). Similarly, the flavonoid supplements had IC50 values of 16.9 mg/mL (EN), 3.44 mg/mL (SB) and 2.72 mg/mL (CB). These values compare with gliptin IC50 values of 0.684 mu M (sitagliptin), 0.707 mu M (saxagliptin) and 2.286 mu M (vildagliptin). The supplement flavonoid content varied from 11.98% (CB) to 5.26% (EN) and 14.51% (SB) of tablet mass, corresponding to daily flavonoid doses of around 300, 150 and 400 mg, respectively, with CB and SB containing rutin at levels of 7.0% and 7.5% of tablet mass, respectively. While our data demonstrated that citrus bioflavonoid based supplements do possess DPP-4 inhibitory activity, they are several orders of magnitude less potent than gliptins. Further studies using higher concentrations of citrus bioflavonoids, as well as investigations into antioxidant properties which may add additional benefit are warranted. (C) 2018 Elsevier Inc. All rights reserved.