Mushroom-Derived Peptide APPLRP Lowers Blood Pressure by Inhibiting ACE and Reducing Vascular Remodeling

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.

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.

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.

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.

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.