Antioxidative and anti-inflammatory potential with trans-epithelial transport of a buffalo casein-derived hexapeptide (YFYPQL)

Inflammation and oxidative stress are two patho-physiological processes that go together. Anti-oxidants can be used as anti-inflammatory mediators to avoid the progression of many lifestyle associated diseases. The overlapping antioxidative and anti-inflammatory potentials of a buffalo casein-derived hexapeptide (YFYPQL) were studied with in vitro and ex vivo assays. An in vitro Caco-2 cell model suggested that pre-treatment with the hexapeptide showed protection against H2O2 induced oxidative cell death and inhibited (p <= 0.01) ROS generation. Peptide treatment also reduced (p <= 0.01) the levels of cellular oxidative products of lipids and proteins (MDA and protein carbonyls) and elevated (p <= 0.05) the activities of the anti-oxidative enzymes (CAT, SOD and GPX) by stimulating the nuclear response factor-2 (Nrf-2) stress signalling pathway. Moreover, peptide treatment reduced (p <= 0.01) the Nrf-2 mRNA expression in Caco-2 cells even in the presence of H2O2. In addition to the antioxidative properties, this peptide also had a role in anti-inflammation with ex vivo conditions by suppressing (p <= 0.01) mice splenocytes proliferation and enhancing the phagocytosis of murine peritoneal macrophages. Peptide treatment was also found to reduce the secretion of pro-inflammatory cytokine (IFN-gamma) and elevated the levels of anti-inflammatory cytokine, IL-10 in splenocytes culture supernatants. Besides, the hexapeptide showed 0.91 +/- 0.04% intact transport across the Caco-2 cell monolayer with an apparent permeability coefficient (P-app) of 4.75x10(-5) cm min(-1) using a transcytosis mediated mechanism. Thus, overlapping antioxidative and antiinflammatory activities as well as transport across the epithelial membrane of the casein hexapeptide was established.