Antioxidant and cytoprotective effects of synthetic peptides identified from Kluyveromyces marxianus protein hydrolysate: Insight into the molecular mechanism

Antioxidant peptide obtained from Kluyveromyces marxianus protein hydrolysate, VLSTSFPPK (VL-9) and peptide analogues were synthesized chemically and analyzed for in vitro and cellular antioxidant activity. VLSTSFCPK (VCK-9), VLSTSFYPK (VYK-9), VLSTSFPPY (VY-9) and VLSTSFPPW(VW-9) showed the highest DPPH radical, ABTS radical cation scavenging and ferric reducing activities. VCK-9, VYK-9 and STSFPPK (SK-7) showed cytoprotective effects against Caco2 cells under H2O2-induced oxidative stress. The positive role of peptides in the protection of cells was shown to be due to scavenging free radicals, activation of Keap1-Nrf2 signaling pathway that may lead to overexpression of antioxidant enzyme genes and also increasing the activity of antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) due to direct interaction with enzymes and changing their conformation. Altogether, pretreatment of cells under oxidative stress with VCK-9, VYK-9 and SK-7 led to decreasing the level of lipid and protein oxidation and cell apoptosis and increasing the cell viability.