A novel angiotensin-converting enzyme (ACE) inhibitory peptide from tilapia skin: Preparation, identification and its potential antihypertensive mechanism

[Display omitted] •Steam explosion improved hydrolysis efficiency and ACE inhibitory activity of fish skin.•A novel ACE inhibitory peptide VGLFPSRSF with a non-competitive binding mode was obtained.•The interaction forces between VGLFPSRSF and the receptor were studied.•Network pharmacology analysis revealed the mechanism of VGLFPSRSF antihypertensive. To obtain food-derived peptides with high ACE inhibitory activity, tilapia skin was pretreated with steam explosion prior to enzymatic hydrolysis. The results showed that steam explosion pretreatment improved the hydrolysis efficiency and ACE inhibitory activity of fish skin hydrolysates. A novel ACE inhibitory peptide VGLFPSRSF (1009.17 Da) was obtained from steam-exploded fish skin hydrolysates. VGLFPSRSF had an IC50 value of 61.43 μM for ACE inhibitory activity, showing a non-competitive binding mode and gastrointestinal enzyme hydrolysis resistance. Molecular docking results showed that VGLFPSRSF interacted with ACE receptor protein through hydrogen bonding and hydrophobic interactions. Based on the results of network pharmacological analysis and molecular docking, VGLFPSRSF might regulate blood pressure through interaction with hypertensive targets such as AKT1, ACE, CD4, REN, and MMP9. Steam-exploded tilapia skin peptides had potential antihypertension activity and might be promising to achieve high-value utilization of fish skin by-products.