# Novel ACE-Inhibitory Peptides from Royal Jelly Proteins: Comprehensive Screening, Mechanistic Insights, and Endothelial Protection

## TL;DR

Researchers discovered new peptides from royal jelly that can inhibit ACE, a key enzyme in blood pressure regulation, and showed they protect blood vessels.

## Contribution

Identification of novel ACE-inhibitory peptides from royal jelly proteins with potential for natural antihypertensive applications.

## Key findings

- PYPDWSFAK and RPYPDWSF exhibited potent ACE-inhibitory activity with IC50 values of 110 ± 1.02 μmol/L and 204 ± 0.61 μmol/L.
- PYPDWSFAK acts as a mixed-type ACE inhibitor and binds strongly with the enzyme's active site.
- PYPDWSFAK suppressed endothelial cell migration and restored NO and ET-1 balance in cellular assays.

## Abstract

This study aimed to identify novel angiotensin-converting enzyme (ACE)-inhibitory peptides from royal jelly proteins (RJPs) by integrating in silico digestion, virtual screening, and in vitro evaluation. Three major royal jelly proteins (MRJP1-3) were subjected to in silico digestion using 16 enzymatic systems, yielding 1411 unique peptides. Virtual screening based on predicted bioactivity, toxicity, water solubility, and ADMET profiles resulted in the selection of 27 candidate peptides. Molecular docking revealed strong binding affinities for these peptides compared with the positive control captopril, among which PYPDWSFAK and RPYPDWSF exhibited potent ACE-inhibitory activity, with IC50 values of 110 ± 1.02 μmol/L and 204 ± 0.61 μmol/L, respectively. Kinetic analysis indicated that PYPDWSFAK acts as a mixed-type ACE inhibitor. Docking visualization demonstrated that PYPDWSFAK forms multiple hydrogen bonds with key residues in the ACE active pocket and directly coordinates with the catalytic Zn2+ ion. Cellular assays showed that PYPDWSFAK was non-cytotoxic, suppressed Ang II–induced endothelial cell migration, restored NO and ET-1 balance, and enhanced SOD and GSH-Px activities. Overall, this study enriches the repertoire of ACE-inhibitory peptides derived from royal jelly proteins. Furthermore, PYPDWSFAK is identified as a promising ACE-inhibitory peptide with potential for incorporation into natural antihypertensive ingredients or functional foods.