Multiple antidiabetic effects of three α-glucosidase inhibitory peptides, PFP, YPL and YPG: Dipeptidyl peptidase-IV inhibition, suppression of lipid accumulation in differentiated 3T3-L1 adipocytes and scavenging activity on methylglyoxal.

Antidiabetic agents with multiple targets have the greatest pharmaceutical potential. In this study, three α-glucosidase inhibitory peptides, PFP, YPL and YPG, were investigated for additional antidiabetic targets viz.; dipeptidyl peptidase-IV inhibition (DPP-IV), lipid accumulation and the differentiation of 3T3-L1 adipocytes, and scavenging of methylglyoxal (MGO), reactive oxygen species (ROS) and nitric oxide (NO). The peptides were subjected to molecular docking on human DPP-IV where the binding free energies were PFP < YPG < YPL < diprotin A while hydrogen bond interactions were critical in the binding of YPL and YPG. Moreover, YPG demonstrated significantly higher (p < 0.05) in vitro DPP-IV inhibition than PFP and YPL. Kinetic analysis revealed that all three peptides are uncompetitive inhibitors of DPP-IV while YPG had the lowest inhibition binding constant. PFP and YPG prevented lipid accumulation in 3T3-L1 differentiated adipocytes but may be due to cytotoxicity for PFP. The peptides scavenged MGO, ROS and NO but only the ROS and NO scavenging activities of YPG were comparable to glutathione. In conclusion, PFP, YPL and YPG exhibited DPP-IV inhibitory activity, reduced adipocyte differentiation and lipid accumulation as well as scavenged MGO, ROS and NO. However, YPG had the best potential as a possible multifunctional antidiabetic agent.