A novel ACE-inhibitory peptide isolated from maitake mushroom (Grifola frondosa) reduced blood pressure and improved vascular remodeling in a zebrafish hypertension model through ACE inhibition and smooth muscle cell modulation.
IC50 = 29.93 μMAPPLRP competitively inhibits ACE at a potency relevant for food-derived bioactive peptides, while also surviving gastrointestinal digestion — a key requirement for oral bioactivity
What the researchers found
APPLRP is a competitive ACE inhibitor with IC50 of 29.93 μM that resists pepsin and pancreatin digestion. In hypertensive zebrafish, it reduced cardiac fibrosis, increased vessel diameter, decreased vessel wall thickness, downregulated ACE expression, and upregulated protective ACE2 expression. In vitro, it blocked Ang II-induced smooth muscle cell proliferation via AT1R/ERK1/2/STAT3 pathway inhibition.
Why it matters
Finding natural food-derived peptides that can lower blood pressure offers potential alternatives or supplements to pharmaceutical ACE inhibitors. The fact that APPLRP survives digestion and works through multiple mechanisms — direct ACE inhibition plus vascular remodeling protection — makes it particularly promising as a functional food ingredient.
The numbers in context
IC50 = 29.93 µM. The peptide was isolated from the alcohol-soluble fraction of Grifola frondosa.
How the study worked
Multi-approach study: computational docking to ACE active site, in vitro smooth muscle cell experiments with Ang II stimulation, and in vivo zebrafish hypertension model with cardiac output, blood flow velocity, collagen deposition, and vessel morphometry measurements. Peptide digestive stability tested against pepsin and pancreatin.
Who was studied
Zebrafish hypertension model and smooth muscle cell cultures
What this study cannot tell us
Zebrafish cardiovascular system differs significantly from human physiology. The IC50 of 29.93 μM, while active, is relatively high compared to pharmaceutical ACE inhibitors. Oral bioavailability in mammals needs testing — digestive stability doesn't guarantee absorption through the gut wall. No mammalian blood pressure data was collected.
How to read the evidence
Preliminary evidence from combined in vitro and zebrafish in vivo studies. The multi-mechanism approach is thorough but translation to mammalian/human cardiovascular effects requires further validation.
When this study was published
Published in 2024, part of the growing field of food-derived bioactive peptides for cardiovascular health.
The bigger picture
Hypertension affects over 1 billion people globally and ACE inhibitors are a cornerstone treatment. Food-derived bioactive peptides could complement pharmaceutical approaches, particularly for borderline hypertension where medication may not be warranted. Maitake mushroom is already consumed worldwide, making this peptide source accessible.
Questions still open
- Would APPLRP maintain its antihypertensive effects when consumed as part of whole maitake mushroom or mushroom extract?
- Can APPLRP be absorbed intact through the human intestinal barrier after surviving digestion?
Common questions
Could eating maitake mushrooms lower blood pressure?
How does this compare to prescription ACE inhibitors like lisinopril?
Read the original research
A novel angiotensin I-converting enzyme inhibitory peptide APPLRP from Grifola frondosa ameliorated the Ang II-induced vascular modeling in zebrafish model by mediating smooth muscle cells.
International journal of biological macromolecules, 278(Pt 4), 134998
Citation
Song, Tianyuan; Zhang, Tiantian; Cai, Qiaolin; Ding, Yin-Yi; Gu, Zhenyu. (2024). A novel angiotensin I-converting enzyme inhibitory peptide APPLRP from Grifola frondosa ameliorated the Ang II-induced vascular modeling in zebrafish model by mediating smooth muscle cells.. International journal of biological macromolecules, 278(Pt 4), 134998. https://doi.org/10.1016/j.ijbiomac.2024.134998