Characterization of casein-derived peptide bioactivity: Differential effects on angiotensin-converting enzyme inhibition and cytokine and nitric oxide production

Abstract

Lactic acid bacteria (LAB) are used as starter cultures in the production of fermented dairy products and have the potential to confer bioactivity relevant to cardiovascular health, as they possess extensive proteolytic systems that liberate small bioactive peptides from larger milk proteins. Certain casein-derived peptides released by various LAB strains during fermentation have been shown to reduce hypertension and to modulate the immune system. We investigated the growth and peptide production of 2 LAB strains, Lactobacillus helveticus R0389 and Lactocaseibacillus rhamnosus R0011, their immunomodulatory activities, as well as their abilities to inhibit the angiotensin-converting enzyme (ACE). Peptide fractions collected from the cell-free supernatant of both medium-grown and milk fermentation cultures were assessed for ACE-inhibitory activity and their effects on the production of proinflammatory and regulatory cytokines by human THP-1 monocytes. Cultures were grown in medium, with or without supplementation with 0.1% casein, or in 3.25% milk fermented with each LAB strain. Casein supplementation increased the growth rate of both LAB strains, and significantly increased ACE-inhibitory activity of peptide fractions collected from both L. helveticus R0389 and L. rhamnosus R0011 cultures grown for 12 h. Fermentation peptide fractions of L. rhamnosus R0011 showed comparable ACE-inhibitory activity to known ACE inhibiting peptides Val-Pro-Pro and Ile-Pro-Pro (up to 79% inhibition) with a significant difference between culture peptide fractions and acidified and nonacidified control fractions collected after 6 d of fermentation. Many milk and casein-derived peptides reported in previous studies have been identified as part of a larger bioactive fraction. We synthesized a group of these peptides to individually assess both ACE-inhibi-tory and immunomodulatory activity. The known ACE inhibitors Val-Pro-Pro and Ile-Pro-Pro showed similar ACE inhibition to previously published results, while also inducing the production of the regulatory cytokine IL-10 by monocytes in the presence and absence of a proinflammatory stimulant. These synthesized peptides could also induce the production of nitric oxide (NO), a potent vasodilator, in human endothelial cell cultures. Investigating the relationships among these bioactive properties could improve the use of probiotic organisms and their secreted products in the food industry.

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

“…Most cytokines, such as IFN-γ, IL-1β, IL-2, IL-6, TNFα can all stimulate the generation of NO [48]. Inhibition of NO synthesis can decrease the production of IL-6 and the cytotoxicity effect of inflammatory cytokines can be blocked by lipid peroxidation inhibitor [49]. Mice deficient in inducible NO synthase exhibited reduced morbidity and mortality when challenged with influenza virus, which told us that NO is the culprits in the virus induced pneumonia death [50].…”

Comparative Peptidomics Analysis of Fermented Milk by Lactobacillus delbrueckii ssp. bulgaricus and Lactobacillus delbrueckii ssp. lactis

“…Specifically, β-casein f (78–91), β-casein f (145–160), and β-casein f (195–206) are only presented in the samples of ssp. bulgaricus, which has been previously reported to produce bioactive peptides with antioxidant [ 26 ], anti-inflammatory [ 27 ], and ACE-inhibitory [ 28 ] activity in vitro, respectively.…”

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

“…Most cytokines, such as IFNγ, IL-1β, IL-2, IL-6, TNFα can all stimulate the generation of NO [48]. Inhibition of NO synthesis can decrease the production of IL-6 and the cytotoxicity effect of in ammatory cytokines can be blocked by lipid peroxidation inhibitor [49]. Mice de cient in inducible NO synthase exhibited reduced morbidity and mortality when challenged with in uenza virus, which told us that NO is the culprits in the virus induced pneumonia death [50].…”