γ-Glutamyl dipeptide (γ-Glu-Val): Dual benefits in reducing vascular inflammation, atherosclerotic plaque formation, and modulating the kokumi taste

Abstract: Dietary γ-glutamyl peptides represent a distinctive class of compounds characterized by the unique presence of a peptide bond formed at the γ-carbon of glutamic acid. Their remarkable impact on enhancing the Kokumi taste sensation arises from their allosteric interaction with calcium-sensing receptors (CaSR), abundantly distributed throughout mammalian tissues, spanning from the tongue to the vascular tissues. In light of the well-established connection between persistent vascular inflammation and the onset of cardiovascular diseases (CVDs), notably atherosclerosis, our recent investigation delved into the specific capabilities of a γ-glutamyl peptide variant, γ-EV, in modulating vascular inflammation through the CaSR-mediated pathway. Our findings suggested the noteworthy anti-inflammatory potential of γ-EV, effectively mitigating tumor necrosis factor-ɑ (TNF-ɑ) induced vascular inflammation via a CaSR-dependent mechanism, specifically by reducing the expression of vascular adhesion molecules (VCAM-1 and E-Selectin) and pro-inflammatory cytokines (IL-6, IL-8) and chemokines (MCP-1). Furthermore, the oral administration of γ-EV demonstrated a significant reduction in the formation of atherosclerotic plaques in Apolipoprotein-E (APO-E) knock-out mice, hinting at its promising role in managing CVDs. Expanding our exploration, we sought to enhance γ-glutamyl peptide concentrations in dry bean flour through a meticulously designed fermentation process involving specific lactic acid bacteria. The resulting peptide-enriched fermented fraction  reduced vascular inflammation in endothelial cells and impart the desired kokumi sensation when put in various food applications. In summary, our research underscores the potent anti-inflammatory attributes of Kokumi-active dietary γ-glutamyl peptides. These insights pave the way for incorporating these peptides into functional foods and highlight their dual benefits in mitigating CVDs and enriching taste experiences.