**5. Conclusions**

New peptides identified from fermented milk were synthesized and analyzed in vitro and in a cellular model for their antioxidant properties. Four of these peptides, **N-15-M**, **E-11-F**, **Q-14-R** and **A-17-E**, were selected for their grea<sup>t</sup> protective e ffects against the action of oxidative stress induced by TbOOH both in the rescue of the viability and in the inhibition of ROS production. The selected bioactive peptides were further studied in order to better understand the mechanism of action of their antioxidant properties. The main conclusion, highlighted by the obtained results, was that the observed protective e ffects against oxidative stress of the antioxidant fermented milk-derived bioactive peptides were mostly due to the activation of Keap1/Nrf2 pathway.

**Supplementary Materials:** The following are available online at http://www.mdpi.com/2076-3921/9/2/117/s1, Figure S1: Fraction 6 uptake from Caco-2 cell monolayer. Cells were incubated in the presence of fraction 6 (150 μg) and the analysis of Apical (AP) and basolateral (BL) compartments was performed at the indicated time. Figure S2: Alignments between the reference proteins and the peptides identified by Proteome Discoverer and Mascot search. Oxidized methionine residues are indicated in lowercase (m); #PSM values are indicated in brackets near to each peptide sequence. The alignments are reported separated for each reference protein. Table S1: Files from ORBITRAP analysis of fraction 6.

**Author Contributions:** Conceptualization: M.P.R. and O.M.; samples production: E.F. and M.B.; extraction and purification of peptides: F.T., L.M. and S.F.; MS/MS analysis: G.A. and F.F.; peptides synthesis: S.F. and O.M.; experiment in cell cultures: F.T., L.M., A.F., V.S. and M.P.R.; molecular docking analysis: A.G.; data curation: F.T., F.F. and L.M.; writing—original draft preparation: M.P.R., O.M., A.B., F.T. and F.F.; writing—review and editing: all authors. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Acknowledgments:** The authors wish to thank the Cassa di Risparmio di Padova e Rovigo Holding (Cariparo) and Veneto Banca Holding for the acquisition of the LTQ-Orbitrap XL mass spectrometer and the MALDI-TOF/TOF mass spectrometer, respectively. In addition, the authors wish to thank Tito Calì for the suggestions and Real-Time PCR facilities.

**Conflicts of Interest:** The authors declare no conflict of interest.
