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Efficacy of Dietary γ-Glutamyl Peptides in Reducing Vascular Inflammation
Cardiovascular diseases (CVDs) are the leading cause of mortality, and its prevalence is estimated at nearly 37% in the United States. Elevated blood glucose, triglycerides, and low levels of high-density lipoprotein, result in increased levels of inflammation and pathogenesis of various CVDs such as atherosclerosis. Dietary γ-glutamyl valine (γ-EV), naturally found in dry beans, have exhibited beneficial biological activities to reduce chronic inflammation. The intervention of γ-EV was found to reduce the inflammatory responses in vascular endothelial cells via the activation of vascular calcium-sensing receptor (CaSR). Human tumor necrosis factor-ɑ (TNF-ɑ) was used to induce inflammation in human aortic endothelial cells (HAECs) pre-treated with γ-EV at 0.01mM, 0.1mM, and 1mM for 2 h. TNF-ɑ-induced increase in inflammatory biomarkers, such as VCAM-1, E-Selectin, chemokine (MCP-1), and cytokines (IL-6 and IL-8), was significantly downregulated by 1mM γ-EV pre-treatment. Furthermore, γ-EV was found to transport across the intestinal monolayer via the PepT1 transporter and paracellular pathways, with the apparent permeability (Papp) of 1.56×10–6 cm/s. The efficacy of γ-EV in reducing vascular inflammation was further evaluated in vivo, in an atherosclerotic mouse model, ApoE-/-. High-fat diet fed ApoE-/- mice significantly showed reduction in the expression of inflammatory biomarkers, VCAM-1, ICAM-1, LOX-1, and MCP-1, and improved the pathological characteristics of theatherosclerotic plaques in the aortas with the γ-EV intervention (150 mg/kg BW) as compared to the mice which didn’t receive γ-EV. In addition, the FoxP3+ expression was significantly increased in the γ-EV-treated group. The study also developed an extraction method for isolating bioactive peptides, including γ-GPs, from Great Northern beans (GNB) and subsequently evaluating their efficacy in reducing vascular inflammation and oxidative stress in human umbilical vein endothelial cells (HUVECs). The bioactive fraction composed of small peptides and phenolics, lesser than 3000 Da in molecular weight, which were able to retain their bioactivities even after gastrointestinal digestion. Thus, the present study highlights the potential use of bean-derived γ-GPs, as a functional food ingredient for the prevention and management of CVDs.
Guha, Snigdha, "Efficacy of Dietary γ-Glutamyl Peptides in Reducing Vascular Inflammation" (2022). ETD collection for University of Nebraska - Lincoln. AAI29322114.