{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:33:06Z","timestamp":1790613186545,"version":"4.1.0"},"reference-count":34,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Universities and Research (MUR)"},{"name":"FSE-REACT-EU"},{"name":"University of Brescia"},{"name":"Interuniversity Consortium for Biotechnology (CIB), Italy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Gamma-oryzanol (ORY), found in rice (Oryza sativa L.), is a mixture of ferulic acid esters with triterpene alcohols, well-known for its antioxidant and anti-inflammatory properties. Our past research demonstrated its positive impact on cognitive function in adult mice, influencing synaptic plasticity and neuroprotection. In this study, we explored whether ORY can exert neuro-differentiating effects by using different experimental models. For this purpose, chemical characterization identified four components that are most abundant in ORY. In human neuroblastoma cells, we showed ORY\u2019s ability to stimulate neurite outgrowth, upregulating the expression of GAP43, BDNF, and TrkB genes. In addition, ORY was found to guide adult mouse hippocampal neural progenitor cells (NPCs) toward a neuronal commitment. Microinjection of ORY in zebrafish Tg (-3.1 neurog1:GFP) amplified neurog1-GFP signal, islet1, and bdnf mRNA levels. Zebrafish nrf2a and nrf2b morphants (MOs) were utilized to assess ORY effects in the presence or absence of Nrf2. Notably, ORY\u2019s ability to activate bdnf was nullified in nrf2a-MO and nrf2b-MO. Furthermore, computational analysis suggested ORY\u2019s single components have different affinities for the Keap1-Kelch domain. In conclusion, although more in-depth studies are needed, our findings position ORY as a potential source of bioactive molecules with neuro-differentiating potential involving the Nrf2 pathway.<\/jats:p>","DOI":"10.3390\/antiox13080969","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T09:48:54Z","timestamp":1723196934000},"page":"969","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Bioactive Gamma-Oryzanol from Oryza sativa L. Promotes Neuronal Differentiation in Different In Vitro and In Vivo Models"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9161-3475","authenticated-orcid":false,"given":"Giulia","family":"Abate","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1788-5880","authenticated-orcid":false,"given":"Alex","family":"Pezzotta","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariachiara","family":"Pucci","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Bortolotto","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroplasticity, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3679-5530","authenticated-orcid":false,"given":"Giovanni","family":"Ribaudo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6571-5910","authenticated-orcid":false,"given":"Sara A.","family":"Bonini","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8862-2896","authenticated-orcid":false,"given":"Andrea","family":"Mastinu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Maccarinelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8661-2416","authenticated-orcid":false,"given":"Alberto","family":"Ongaro","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Tirelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0451-8029","authenticated-orcid":false,"given":"Daniela","family":"Zizioli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-5163","authenticated-orcid":false,"given":"Alessandra","family":"Gianoncelli","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7543-0289","authenticated-orcid":false,"given":"Maurizio","family":"Memo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9165-5827","authenticated-orcid":false,"given":"Mariagrazia","family":"Grilli","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroplasticity, University of Piemonte Orientale, 28100 Novara, Italy"},{"name":"Department of Pharmaceutical Sciences, University of Piemonte Orientale, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5926-9122","authenticated-orcid":false,"given":"Daniela","family":"Uberti","sequence":"additional","affiliation":[{"name":"Department of Molecular and Translational 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