Researchers identified a peptide called PYPDWSFAK from royal jelly that effectively inhibits ACE — a key enzyme in blood pressure regulation — and protects blood vessel cells from damage.
IC50 = 110 μmol/LThe ACE-inhibitory potency of PYPDWSFAK, the most effective peptide identified from royal jelly proteins
What the researchers found
From three major royal jelly proteins (MRJP1-3), 1,411 unique peptides were generated through simulated digestion. After virtual screening for bioactivity, safety, and drug-like properties, 27 candidates were selected. Two peptides — PYPDWSFAK and RPYPDWSF — showed potent ACE inhibition with IC50 values of 110 μmol/L and 204 μmol/L, respectively.
PYPDWSFAK acted as a mixed-type ACE inhibitor, forming multiple hydrogen bonds with key residues in the ACE active site and directly coordinating with the catalytic zinc ion. In cell studies, PYPDWSFAK was non-toxic, blocked angiotensin II-induced endothelial cell migration, restored the balance of nitric oxide (NO) and endothelin-1 (ET-1), and boosted antioxidant enzyme activities (SOD and GSH-Px).
Why it matters
High blood pressure is one of the most common chronic health conditions worldwide, and many people seek natural alternatives to pharmaceutical ACE inhibitors like captopril. Identifying potent ACE-inhibitory peptides from a natural source like royal jelly opens the door to developing functional foods or supplements that could help manage blood pressure with fewer side effects.
How the study worked
The researchers used computer simulations to digest three major royal jelly proteins with 16 different enzyme combinations, generating 1,411 unique peptide fragments. These were screened virtually for predicted bioactivity, toxicity, solubility, and drug-like properties. The top 27 candidates were tested in molecular docking simulations against ACE, and the best performers were validated in lab-based ACE inhibition assays and cell culture experiments using endothelial cells.
What this study cannot tell us
This study was conducted entirely in computer simulations and cell cultures — there were no animal or human trials to confirm whether these peptides lower blood pressure in a living organism. The peptides' stability during actual digestion, their absorption in the gut, and their bioavailability in the bloodstream remain unknown. The IC50 values, while promising, are higher than captopril, meaning larger doses might be needed for a therapeutic effect.
How to read the evidence
This is an in silico and in vitro study combining computational screening with cell culture validation. While the multi-step screening approach is rigorous, the findings have not been confirmed in animal models or human trials, placing this at a preclinical evidence level.
When this study was published
Published in 2025, this is a very recent study using current computational and cell biology methods. The findings are at the cutting edge of food-derived peptide research.
The bigger picture
This research adds to a growing body of work on food-derived bioactive peptides as natural alternatives to synthetic drugs. ACE-inhibitory peptides have been found in milk, fish, and soy proteins, and royal jelly now joins that list. The comprehensive screening approach used here — combining computational prediction with lab validation — represents a modern pipeline for discovering therapeutic peptides from natural protein sources.
Questions still open
- Can PYPDWSFAK survive digestion and reach the bloodstream in sufficient quantities to inhibit ACE in vivo?
- How does the ACE-inhibitory potency of these royal jelly peptides compare to peptides from other food sources in animal models of hypertension?
- Could these peptides be combined with other natural antihypertensive compounds for a synergistic effect?
Common questions
What is ACE and why does blocking it matter for blood pressure?
Could eating royal jelly lower blood pressure?
Read the original research
Novel ACE-Inhibitory Peptides from Royal Jelly Proteins: Comprehensive Screening, Mechanistic Insights, and Endothelial Protection.
Foods (Basel, Switzerland), 15(1)
Citation
Yang, Wanyu; Zou, Xinyu; Zhang, Tianrong; Liu, Qingqing; Liu, Ziyan; Li, Fan; Luo, Yuhong; Wang, Yiwen; Qiu, Zhijun; Zhang, Bin. (2025). Novel ACE-Inhibitory Peptides from Royal Jelly Proteins: Comprehensive Screening, Mechanistic Insights, and Endothelial Protection.. Foods (Basel, Switzerland), 15(1). https://doi.org/10.3390/foods15010084