Food Res Int. 2026 Mar 1;227:118300. doi: 10.1016/j.foodres.2025.118300. Epub 2025 Dec 30.
ABSTRACT
Hypertension, a major global health issue, is closely associated with the overactivation of angiotensin-converting enzyme (ACE). Food-derived ACE inhibitory peptides are gaining increasing attention as natural alternatives to synthetic antihypertensive drugs due to their safety and efficacy. In this study, an integrated computational-experimental workflow was developed to discover novel ACE-inhibitory peptides from food proteins. Using molecular docking, descriptor-based clustering, and in silico enzymatic hydrolysis, quinoa protein was identified as a rich source of potential ACE inhibitors. Subsequent in vitro hydrolysis and LC-MS/MS analysis yielded four new peptides-IDL, VSF, IEL, and EVF. Among these peptides, IDL and VSF showed the strongest ACE inhibitory activities during the preliminary screening, and thus were selected for further investigation. The two peptides exhibited potent ACE inhibition (IC = 65.2 and 15.4 μM, respectively) via competitive binding to the ACE active site, along with excellent thermal, pH, and digestive stability. Additionally, they significantly enhanced endothelial nitric oxide synthase (eNOS) activity. In spontaneously hypertensive rats, IDL and VSF effectively reduced blood pressure, alleviated vascular fibrosis, and restored ACE-Ang II-AT1R and ACE2-Ang (1-7)-Mas axis balance. These findings highlight an efficient strategy for identifying natural ACE inhibitors and support the potential of quinoa-derived peptides in antihypertensive functional food development.
PMID:41652705 | DOI:10.1016/j.foodres.2025.118300