Transport and action of sesame protein-derived ACE inhibitory peptides ITAPHW and IRPNGL

Vascular endothelial dysfunction is an important pathogenic factor in hypertension, in which angiotensin-converting enzyme (ACE) plays an important role. Peptides that bind to ACE may attenuate vascular endothelial dysfunction by altering the structure of ACE. This study demonstrated that ITAPHW and IRPNGL were resistant to simulated gastrointestinal fluid and were transported across the Caco-2 monolayer via the intercellular space, with ITAPHW showing a high apparent permeability coefficient of (1.44 ± 0.01) × 10^-5 cm/s. Subsequently, multispectral analysis and molecular dynamic simulation revealed the stability, conformation changes, and potential binding sites of ITAPHW- and IRPNGL-ACE complex. Furthermore, ITAPHW and IRPNGL alleviated endothelial dysfunction in the angiotensin I-induced human umbilical vein endothelial cells (HUVECs) by reducing ACE activity and the concentrations of angiotensin II and endothelin-1 (ET-1), while promoting the level of nitric oxide (NO), endothelial nitric oxide synthase (eNOS), cyclic guanosine 3', 5'-monophosphate (cGMP), and ACE2.