Anti-inflammatory Effect and Cellular Uptake Mechanism of Peptides from Common Bean (Phaseolus vulga L.) Milk and Yogurts in Caco-2 Mono- and Caco-2/EA.hy926 Co-culture Models

Naturally occurring dietary peptides derived from gastrointestinal digestates of common bean milk and yogurt were studied for their bioaccessibility, bioavailability, and anti-inflammatory activity in both Caco-2 mono- and Caco-2/EA.hy926 co-culture cell models. Anti-inflammatory activities of these peptide extracts were found to be strongly associated with cellular uptake by the intestinal epithelial cells. Mechanisms underlying the cellular uptake were studied by examining the role of peptide transporter 1 and calcium sensing reporter. Three peptides, including gamma-glutamyl-S-methylcysteine, gamma-glutamyl-leucine, and leucine-leucine-valine, were found to be transported across the Caco-2 cell monolayer and detected by liquid chromatography-tandem mass spectrometry. A strong anti-inflammatory effect was observed in the basolateral EA.hy926 cells (co-culture model), as shown in their inhibition of tumor necrosis factor alpha-induced pro-inflammatory mediators of the nuclear factor kappa B and mitogen-activated protein kinase signal cascades. The results suggest that these peptides can be absorbed and possibly have systemic inhibition on inflammatory responses in vascular endothelial cells, indicating potential preventive effects on vascular diseases.