Recent findings on the cellular and molecular mechanisms of action of novel food-derived antihypertensive peptides

Abstract

Hypertension impacts negatively on the quality of life of sufferers, and complications associated with uncontrolled hypertension are life-threatening. Hence, many research efforts are exploring the antihypertensive properties of bioactive peptides derived from food proteins using in vitro ACE-inhibitory assay, experimentally-induced and spontaneous hypertensive rats, normotensive and hypertensive human models. In this study, the cellular and molecular mechanisms of blood pressure-lowering properties of novel peptides reported in recent studies (2015-July 30, 2021) were discussed. In addition to common mechanisms such as the inhibition of angiotensin I-converting enzyme (ACE) and renin activities, recently recognized mechanisms through which bioactive peptides exert their antihypertensive properties including the induction of vasodilation via upregulation of cyclo-oxygenase (COX) and prostaglandin receptor and endothelial nitric oxide synthase expression and L-type Ca2+ channel blockade were presented. Similarly, emerging mechanisms of blood pressure-lowering by bioactive peptides such as modulation of inflammation (TNF-α, and other cytokines signaling), oxidative stress (Keap-1/Nrf2/ARE/HO-1 and related signaling pathways), PPAR-γ/caspase3/MAPK signaling pathways and inhibition of lipid accumulation were discussed. The review also highlighted factors that influence the antihypertensive properties of peptides such as method of hydrolysis (type and number of enzymes, and chemical used for hydrolysis, and microbial fermentation), and amino acid sequence and chain length of peptides.