Novel angiotensin-I-converting enzyme (ACE) inhibitory peptides from Porphyra haitanensis: Screening, digestion stability, and mechanistic insights

Food-derived peptides with angiotensin-I-converting enzyme inhibitory (ACEI) activity have garnered significant research attention. This study focused on examining ACEI peptides from Porphyra haitanensis and investigating their potential inhibitory mechanisms through a combination of in silico and in vitro methods. Five novel potential ACEI peptides (ASF: Ala-Ser-Phe, EIIL: Glu-Ile-Ile-Leu, LCVPR: Leu-Cys-Val-Pro-Arg, LDVVN: Leu-Asp-Val-Val-Asn, and LSPSW: Leu-Ser-Pro-Ser-Trp) were identified through a combination of peptidomics and in silico bioinformatics analysis, of which LSPSW showed the highest activity (IC 50 : 5.27 ± 0.53 μM). After simulated gastrointestinal digestion (SGD), the activities of LCVPR and LSPSW remained almost unchanged. The results from inhibition kinetics and molecular docking demonstrated that ACEI peptides with differing inhibition mechanisms could successfully bind to ACE through hydrogen bonds. Based on network pharmacology analysis and cellular experiments, LSPSW exerted antihypertensive effects by regulating the expression levels of peroxisome proliferator activated receptor gamma (PPARG), prostaglandin-endoperoxide synthase 2 (PTGS2), and renin (REN). This research provided a novel theoretical foundation for the high-value application of P. haitanensis .