RT Journal Article T1 A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD-fed ApoE−/− mice A1 Santos-Sánchez, Guillermo A1 Ponce-España, Eduardo A1 Álvarez-López, Ana Isabel A1 Pedroche, Justo A1 Millán-Linares, María del Carmen A1 Fernández-Pachón, María-Soledad A1 Lardone, Patricia Judith A1 Cruz-Chamorro, Ivan A1 Carrillo-Vico, Antonio K1 Brain K1 Glutathione K1 iNOS K1 Nitric oxide K1 Peptides AB Oxidative stress plays a crucial role in neurodegenerative diseases like Parkinson’s and Alzheimer’s. Studies indicate the relationship between oxidative stress and the brain damage caused by a high-fat diet. It is previously found that a lupin protein hydrolysate (LPH) has antioxidant effects on human leukocytes, as well as on the plasma and liver of Western diet (WD)-fed ApoE−/− mice. Additionally, LPH shows anxiolytic effects in these mice. Given the connection between oxidative stress and anxiety, this study aimed to investigate the antioxidant effects of LPH on the brain of WD-fed ApoE−/− mice. LPH (100 mg kg−1) or a vehicle is administered daily for 12 weeks. Peptide analysis of LPH identified 101 amino acid sequences (36.33%) with antioxidant motifs. Treatment with LPH palliated the decrease in total antioxidant activity caused by WD ingestion and regulated the nitric oxide synthesis pathway in the brain of the animals. Furthermore, LPH increased cerebral glutathione levels and the activity of catalase and glutathione reductase antioxidant enzymes and reduced the 8-hydroxy-2’-deoxyguanosine levels, a DNA damage marker. These findings, for the first time, highlight the antioxidant activity of LPH in the brain. This hydrolysate could potentially be used in future nutraceutical therapies for neurodegenerative diseases. PB Wiley Online Library YR 2024 FD 2024 LK https://hdl.handle.net/10433/20551 UL https://hdl.handle.net/10433/20551 LA en NO A lupin protein hydrolysate protects the central nervous system from oxidative stress in WD-fed ApoE−/− mice. Mol. Nutr. Food Res. 2024, 68, 2300503. NO This research was funded by the Andalusian GovernmentMinistry of Health PC-0111-2016-0111, PEMP-0085-2020 (co-financed with FEDER funds, call Resolution of 7 July 2021 of the General Secretary for Research, Development and Innovation in Health, which calls for grants to finance research, development and innovation in biomedicine and health sciences in Andalusia by 2021) and the PAIDI Program from the Andalusian Government [CTS160]. G.S.-S. was supported by FPU grants from the Spanish Ministerio de Educación, Cultura y Deporte, [FPU16/02339]. I.C.-C. was supported by a postdoctoral fellowship from the Andalusian Government Ministry of Economy, Knowledge, Business, and University [DOC_00587/2020]. A.I.A.-L. was funded by the Andalusian Government Ministry of Health [PI-0136-2019]. E.P.-E. was supported by the VI Program of Inner Initiative for Research and Transfer of the University of Seville [VI PPIT-US]. NO Universidad Pablo de Olavide DS RIO RD May 23, 2026