Identification and in silico screening of novel angiotensin-converting enzyme inhibitory peptides from pacific saury: Interaction mechanism, network pharmacology, stability, Caco-2 monolayer transport

Abstract

Angiotensin-converting enzyme (ACE) inhibitory peptides (ACEIPs) have garnered enormous attention in maintaining blood pressure balance of humans. In this study, the amino acid sequence of Pacific saury ultrafiltration fraction was identified by Nano-LC-Q-Orbitrap-MS/MS. Through in silico screening, eight novel ACEIPs were elected to synthesize, among of which the VFPLK (IC50 value of 60.7 μΜ) exhibited the strongest ACE inhibitory ability. The interaction mechanism of VFPLK and ACE was explored. To be specific, the VFPLK was a mix pattern based on the Lineweaver–Burk plot, formed six hydrogen bonds with ACE according to the molecular docking and exhibited good affinity with ACE by molecular dynamic simulation. The core targets of VFPLK against hypertension were predicted to be ALB, AKT1, MMP9, IGF1 and NOS3 by network pharmacology. Besides, VFPLK showed good stability in temperature, pH and gastrointestinal digestion. Moreover, the apparent permeability coefficient of VFPLK was determined to be 1.09 × 10−6 cm/s, and paracellular transport via tight junctions was the primary pathway across the Caco-2 cell monolayer. Finally, the concentration 0.2–1.5 mg/mL of VFPLK disclosed no toxicity for EA.hy26. Collectively, VFPLK could be a beneficial constituent in nutraceuticals and functional foods for combating antihypertensive and related diseases.