A peptide called DIGGL isolated from the edible green alga Ulva prolifera inhibited ACE with an IC50 of 10.32 μM, boosted nitric oxide production, and survived simulated digestion intact.
IC50 = 10.32 μMDIGGL inhibits ACE at a low micromolar concentration and remains active after simulated gastrointestinal digestion
What the researchers found
The peptide DIGGL was identified from Ulva prolifera protein hydrolysates with an IC50 value of 10.32 ± 0.96 μM for ACE inhibition, acting through a non-competitive mechanism primarily via three conventional hydrogen bonds with the enzyme.
In human umbilical vein endothelial cells, DIGGL activated endothelial nitric oxide synthase to increase NO production and reduced endothelin-1 secretion induced by angiotensin II. The peptide also promoted mouse splenocyte proliferation both alone and when co-incubated with immune stimulants (Con A or LPS), indicating immunomodulatory properties. Crucially, DIGGL remained active after simulated gastrointestinal digestion with pepsin and trypsin.
Why it matters
Finding natural food-derived peptides that can lower blood pressure is a growing area of research for developing functional foods and nutraceuticals. DIGGL is particularly promising because it comes from an abundant, edible seaweed, works at low concentrations, has multiple beneficial mechanisms (ACE inhibition plus nitric oxide boost), and survives digestion — a major hurdle for oral peptide bioactivity.
How the study worked
Researchers isolated protein from Ulva prolifera and hydrolyzed it using five commercial enzymes individually and in combination. The hydrolysate with the highest ACE inhibitory activity was purified through gel filtration, ultrafiltration, and HPLC-Q-TOF-MS. Computational ADMET screening and molecular docking were used to characterize the peptide-ACE interaction. Functional assays were performed on human endothelial cells and mouse splenocytes, and gastrointestinal stability was tested with simulated digestion.
What this study cannot tell us
All experiments were conducted in vitro or in cell culture — there are no animal or human studies showing that DIGGL lowers blood pressure when consumed. The gastrointestinal stability test was simulated, not performed in a living system. Bioavailability (whether the peptide is absorbed into the bloodstream) was not assessed. The immunomodulatory effects on splenocytes need further investigation for relevance.
How to read the evidence
This is a preclinical laboratory study with in vitro enzyme assays, cell culture experiments, and computational modeling. While the findings are promising, no animal or human studies have been conducted to validate the blood pressure-lowering effect.
When this study was published
Published in 2023, this study represents recent work in the active field of marine-derived bioactive peptides for cardiovascular health.
The bigger picture
This work contributes to the broader effort to develop bioactive peptides from marine sources as natural alternatives or supplements to pharmaceutical ACE inhibitors. Seaweed-derived peptides are particularly attractive because seaweed is abundant, sustainable, and already consumed as food in many cultures. The dual cardiovascular and immunomodulatory activity of DIGGL adds to its potential as a functional food ingredient.
Questions still open
- Does DIGGL actually lower blood pressure when consumed orally in animal models or humans?
- Is the peptide absorbed intact through the intestinal wall into the bloodstream?
- Could Ulva prolifera be developed as a commercial source of blood pressure-lowering functional food ingredients?
Common questions
What is ACE and why does inhibiting it matter for blood pressure?
Can you eat this seaweed to lower blood pressure?
Read the original research
Purification identification and function analysis of ACE inhibitory peptide from Ulva prolifera protein.
Food chemistry, 401, 134127
Citation
Li, Zhiyong; He, Yuan; He, Hongyan; Zhou, Weizhe; Li, Mengru; Lu, Aiming; Che, Tuanjie; Shen, Songdong. (2023). Purification identification and function analysis of ACE inhibitory peptide from Ulva prolifera protein.. Food chemistry, 401, 134127. https://doi.org/10.1016/j.foodchem.2022.134127