{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T01:12:04Z","timestamp":1788743524018,"version":"build-2803163510"},"reference-count":84,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Current Research Funds 2025, Ministry of Health, Italy","doi-asserted-by":"publisher","award":["RRC-2025-23696388"],"award-info":[{"award-number":["RRC-2025-23696388"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Cannabis sativa is a remarkable source of bioactive compounds, with over 150 distinct phytocannabinoids identified to date. Among these, cannabinoids are gaining attention as potential therapeutic agents for neurodegenerative diseases. Previous research showed that cannabinol (CBN), a minor cannabinoid derived from \u03949-tetrahydrocannabinol, exhibits antioxidant, anti-inflammatory, analgesic, and anti-bacterial effects. The objective of this study was to assess the protective potential of 24 h CBN pre-treatment, applied at different concentrations (5 \u00b5M, 10 \u00b5M, 20 \u00b5M, 50 \u00b5M, and 100 \u00b5M), in differentiated neuroblastoma \u00d7 spinal cord (NSC-34) cells. Transcriptomic analysis was performed using next-generation sequencing techniques. Our results reveal that CBN had no negative impact on cell viability at the tested concentrations. Instead, it showed a significant effect on stress response and neuroplasticity-related processes. Specifically, based on the Reactome database, the biological pathways mainly perturbed by CBN pre-treatment were investigated. This analysis highlighted a significant enrichment in the Reactome pathway\u2019s cellular response to stress, cellular response to stimuli, and axon guidance. Overall, our results suggest that CBN holds promise as an adjuvant agent for neurodegenerative diseases by modulating genes involved in neuronal cell survival and axon guidance.<\/jats:p>","DOI":"10.3390\/antiox14060744","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T03:37:07Z","timestamp":1750131427000},"page":"744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cannabinol\u2019s Modulation of Genes Involved in Oxidative Stress Response and Neuronal Plasticity: A Transcriptomic Analysis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3846-0785","authenticated-orcid":false,"given":"Serena","family":"Silvestro","sequence":"first","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2082-9855","authenticated-orcid":false,"given":"Marco","family":"Calabr\u00f2","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Trainito","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Salamone","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Eastern Piedmont, Largo Donegani 2, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0949-2799","authenticated-orcid":false,"given":"Federica","family":"Pollastro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Eastern Piedmont, Largo Donegani 2, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Mazzon","sequence":"additional","affiliation":[{"name":"Department of Medical, Oral and Biotechnological Sciences, University \u201cG. d\u2019Annunzio\u201d Chieti-Pescara, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4112-5542","authenticated-orcid":false,"given":"Aurelio","family":"Minuti","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.lfs.2005.09.011","article-title":"Chemical constituents of marijuana: The complex mixture of natural cannabinoids","volume":"78","author":"Elsohly","year":"2005","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pagano, C., Navarra, G., Coppola, L., Avilia, G., Bifulco, M., and Laezza, C. 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