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Given the limited efficacy of current therapies, natural compounds with multitarget neuroprotective potential are of growing interest. In this study, we investigated the neuroprotective effects of a standardized Magnolia officinalis (L.) bark extract (MOE) in rat brain cortical slices exposed to hydrogen peroxide-induced OS. MOE significantly recovered tissue viability and reduced ROS and malondialdehyde levels caused by OS while attenuating caspase-3, -8, and -9 activation, suggesting modulation of intrinsic and extrinsic apoptotic pathways. Shotgun proteomics using LC-HRMS\/MS identified OS-induced protein expression changes reversed by MOE, with fourteen of thirty-three altered proteins rescued by MOE co-treatment. These proteins participate in several processes, including neuronal survival, OS response, and proteostasis. Bioinformatic analysis demonstrated that genes responsible for protein synthesis regulated by MOE are subjected to transcriptional regulation by factors associated with OS, including FOXO4, NRF2, and SP1. The present findings support the hypothesis that MOE exerts multitarget neuroprotective effects by modulating key proteins involved in OS responses and neuronal survival in an acute ex vivo oxidative injury model, suggesting potential relevance for mechanisms associated with NDs.<\/jats:p>","DOI":"10.3390\/ijms27083350","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T15:26:39Z","timestamp":1775661999000},"page":"3350","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Magnolia officinalis (L.) Bark Extract Counteracts Oxidative Brain Injury: A Proteomic Investigation into Neuroprotective Mechanisms"],"prefix":"10.3390","volume":"27","author":[{"given":"Laura Beatrice","family":"Mattioli","sequence":"first","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum Universit\u00e0 di Bologna, Via Belmeloro 6, 40126 Bologna, Italy"},{"name":"Centro Interdipartimentale di Ricerca Industriale\u2014CIRI Scienze Della Vita e Tecnologie per la Salute, Alma Mater Studiorum Universit\u00e0 di Bologna, Via Belmeloro 6, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1462-4423","authenticated-orcid":false,"given":"Roberto","family":"Stella","sequence":"additional","affiliation":[{"name":"Dipartimento di Chimica, Istituto Zooprofilattico Sperimentale Delle Venezie, Viale dell\u2019Universit\u00e0 10, 35020 Legnaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9967-2629","authenticated-orcid":false,"given":"Caterina","family":"Peggion","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia, Universit\u00e0 di Padova, via Ugo Bassi 58\/b, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7271-4625","authenticated-orcid":false,"given":"Stefano","family":"Cagnin","sequence":"additional","affiliation":[{"name":"Dipartimento di Biologia, Universit\u00e0 di Padova, via Ugo Bassi 58\/b, 35131 Padova, Italy"},{"name":"CIR-Myo Myology Center, Universit\u00e0 di Padova, via Ugo Bassi 58\/b, 35131 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Pifferi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Della Vita, Universit\u00e0 di Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-8624","authenticated-orcid":false,"given":"Elisabetta","family":"Miraldi","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Fisiche, Della Terra e dell\u2019Ambiente, Universit\u00e0 di Siena, Via Laterina 8, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2037-3133","authenticated-orcid":false,"given":"Giorgio","family":"Cappellucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Fisiche, Della Terra e dell\u2019Ambiente, Universit\u00e0 di Siena, Via Laterina 8, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Baini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Fisiche, Della Terra e dell\u2019Ambiente, Universit\u00e0 di Siena, Via Laterina 8, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6731-5686","authenticated-orcid":false,"given":"Luca","family":"Camarda","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum Universit\u00e0 di Bologna, Via Belmeloro 6, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-9740","authenticated-orcid":false,"given":"Roberta","family":"Budriesi","sequence":"additional","affiliation":[{"name":"Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum Universit\u00e0 di Bologna, Via Belmeloro 6, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4452-8128","authenticated-orcid":false,"given":"Maria","family":"Frosini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Della Vita, Universit\u00e0 di Siena, Via Aldo Moro 2, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","first-page":"2937","article-title":"The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need","volume":"16","author":"Wang","year":"2024","journal-title":"Aging Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","article-title":"Hallmarks of Neurodegenerative Diseases","volume":"186","author":"Wilson","year":"2023","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41582-019-0244-7","article-title":"Ageing as a Risk Factor for Neurodegenerative Disease","volume":"15","author":"Hou","year":"2019","journal-title":"Nat. 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