Using targeted affinity purification and computational screening, researchers identified three ACE-inhibiting peptides from sea cucumber gonads, with HDWWKER significantly reducing blood pressure in spontaneously hypertensive rats after intravenous administration.
Significant SBP reduction in SHRsHDWWKER from sea cucumber gonads lowered blood pressure in hypertensive rats after IV administration — one of few marine peptides with in vivo antihypertensive validation
What the researchers found
The sea cucumber-derived peptide HDWWKER significantly decreased systolic blood pressure in spontaneously hypertensive rats after IV administration, validating targeted affinity purification combined with computational drug discovery for ACE inhibitor screening.
Why it matters
This study validates a novel pipeline: targeted affinity purification + computational screening → in vivo blood pressure reduction. Most food-derived ACE inhibitor studies stop at in vitro testing. Demonstrating actual blood pressure lowering in hypertensive animals significantly strengthens the case for marine-derived antihypertensive peptides.
The numbers in context
Peptides smaller than 3 kDa showed the best ACE inhibitory activity. Multiple peptide sequences were identified and confirmed by molecular docking.
How the study worked
Alcalase hydrolysis of sea cucumber gonads → ultrafiltration (<3 kDa) → ACE gel affinity chromatography → RP-HPLC → LC-MS/MS identification → SBVS filtering (20 peptides) → synthesis of top 3 → ACE inhibition kinetics → molecular docking and dynamics → SHR blood pressure testing (IV administration).
Who was studied
In vitro enzyme assay
What this study cannot tell us
HDWWKER was tested IV, not orally — oral bioavailability is unknown. The IC50 values are relatively high compared to pharmaceutical ACE inhibitors. Only short-term blood pressure effects assessed. Noncompetitive inhibition mechanism is less potent than competitive. Affinity purification introduces bias toward certain binding modes.
How to read the evidence
Preliminary-to-moderate — combines in vitro ACE inhibition with in vivo blood pressure reduction in a disease model (SHRs). Stronger than most food peptide studies, but IV-only administration and lack of oral bioavailability data are significant gaps.
When this study was published
Published in 2024, advancing the application of targeted affinity purification and CADD in marine peptide drug discovery.
The bigger picture
Sea cucumbers are a luxury food in Asian cuisine and a growing aquaculture product. Identifying antihypertensive peptides from their gonads (often a processing byproduct) adds value to the supply chain while potentially creating new nutraceutical products. The methodology combining affinity chromatography with computational screening is broadly applicable to other marine protein sources.
Questions still open
- Does HDWWKER lower blood pressure when administered orally, or is it degraded during digestion?
- Could HDWWKER be developed as a nutraceutical supplement, and what oral dose would be needed?
- Are there more potent ACE-inhibiting peptides in other sea cucumber tissues or species?
Common questions
Could eating sea cucumber lower blood pressure?
What is ACE gel affinity chromatography?
Read the original research
Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads.
Marine drugs, 22(2)
Citation
Wang, Yangduo; Chen, Shicheng; Shi, Wenzheng; Liu, Shuji; Chen, Xiaoting; Pan, Nan; Wang, Xiaoyan; Su, Yongchang; Liu, Zhiyu. (2024). Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads.. Marine drugs, 22(2). https://doi.org/10.3390/md22020090