A combined in vitro and in silico study of the inhibitory mechanism of angiotensin-converting enzyme with peanut peptides.

Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.