ACE-Inhibiting Peptide from Pacific Saury Lowers Blood Pressure in Hypertensive Rats and Crosses Intestinal Barrier

The Pacific saury peptide LEPWR inhibits ACE (IC50: 99.5 μM) through mixed competitive inhibition with 6 hydrogen bonds, and demonstrates intestinal absorption via paracellular transport (Papp: 3.56×10⁻⁶ cm/s) through Caco-2 monolayers.

Bioactivity-guided purification of Pacific saury hydrolysates via ultrafiltration, Sephadex G-25, and RP-HPLC. Antihypertensive effect confirmed in SHR model. Peptide identification by Q-Orbitrap-MS/MS. Molecular docking for binding analysis. Caco-2 monolayer transport studies with apparent permeability measurement and transport route characterization.

This study goes beyond most food peptide research by demonstrating both in vivo blood pressure reduction AND intestinal absorption — the two critical requirements for a food-derived peptide to actually work as an oral antihypertensive. The paracellular transport route provides a mechanistic explanation for how small peptides from food can reach the bloodstream.

This is one of a handful of studies that demonstrate the full pipeline for food-derived ACE inhibitors: identification, in vitro potency, intestinal absorption, and in vivo blood pressure effect. The intestinal transport data via tight junctions is particularly valuable, as it explains the mechanism by which small food peptides bypass the intestinal barrier. Pacific saury joins tuna, mackerel, and other fish as validated sources of bioactive antihypertensive peptides.

The SHR blood pressure reduction was shown for the crude hydrolysate fraction, not purified LEPWR specifically. The IC50 of 99.5 μM is moderate — higher doses would be needed. Caco-2 monolayers are a model, not real intestine. Long-term antihypertensive effect and dose-response relationship in animals not established. Papp of 3.56×10⁻⁶ cm/s indicates moderate absorption, not high.