Preparation, Bioavailability, and Mechanism of Emerging Activities of Ile‐Pro‐Pro and Val‐Pro‐Pro

Abstract

Ile‐Pro‐Pro and Val‐Pro‐Pro are two most well‐known food‐derived bioactive peptides, initially identified as inhibitors of angiotensin I‐converting enzyme (ACE) from a sample of sour milk. These two peptides were identified in fermented and enzymatic hydrolyzed cow and non‐cow (that is, goat, sheep, buffalo, yak, camel, mare, and donkey) milk, as well as sourdough prepared from wheat, rye, and malt. Similar to other bioactive peptides, bioavailability of these peptides is low (about 0.1%), reaching picomolar concentration in human plasma; they showed blood pressure lowering activity in animals and in human, via improved endothelial function, activation of ACE2, and anti‐inflammatory property. Emerging bioactivities of these two peptides toward against metabolic syndrome and bone‐protection received limited attention, but may open up new applications of these peptides as functional food ingredients. Further studies are warranted to determine the best source as well as to identify novel enzymes (particularly from traditional fermented milk products) to improve the efficiency of production, to characterize possible peptide receptors using a combination of omics technology with molecular methods to understand if these two peptides act as signal‐like molecules, to improve their bioavailability, and to explore new applications based on emerging bioactivities.

Bioprospecting for Bioactive Peptide Production by Lactic Acid Bacteria Isolated from Fermented Dairy Food

“…Among the anti-hypertensive peptides found in FDFs, the lactotripeptides, VPP and IPP, gained great attention in recent years thanks to their increasingly frequent commercial use in hypotensive milk-drinks production. Indeed, numerous in vivo studies reported a blood pressure reduction in mildly hypertensive patients [23,51,75,76]. These lactotripeptides were initially detected in a sample of Japanese sour milk fermented by Lactobacillus helveticus and Saccharomyces cerevisiae and characterized for their ACE-inhibitory (ACE-i) activity and hypotensive effect in spontaneously hypertensive rats [52,77].…”

Bioactive peptides from food fermentation: A comprehensive review of their sources, bioactivities, applications, and future development

“…The prominent examples from milk‐ and milk product‐derived ACE‐I peptides are VPP and IPP, which have received comprehensive review recently (Li et al., 2019). VPP and IPP were found to be degradation resistant and were able to exert ACE inhibition in aorta (Li et al., 2019). The IC 50 values of VPP (5 µM) and IPP (9 µM) are much higher than that of captopril (0.007 µM) (Li et al., 2019).…”

“…VPP and IPP were found to be degradation resistant and were able to exert ACE inhibition in aorta (Li et al., 2019). The IC 50 values of VPP (5 µM) and IPP (9 µM) are much higher than that of captopril (0.007 µM) (Li et al., 2019). By observation, both peptides fulfilled the structure–activity requirement of branched hydrophobic amino acid (valine and isoleucine) at the N‐terminus and the presence of aromatic hydrophobic amino acid (proline) at the C‐terminus.…”

The Potential of Food Protein-Derived Bioactive Peptides against Chronic Intestinal Inflammation

“…Along with the above two pathways, the JAK-STAT pathway is also important for inflammatory response and can regulate hematopoietic cell development and inflammatory cytokines. Phosphorylation of JAK and STATs can form the dimer translocated to the nucleus [ 38 ]. BAPs can attenuate inflammation by inhibiting phosphorylation of JAK and STATs.…”