{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:04:54Z","timestamp":1770743094333,"version":"3.49.0"},"reference-count":106,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Flavonoids are a diverse group of natural polyphenolic compounds, recognized for their ability to modulate cellular pathways and mitigate the pathological processes of many neurodegenerative diseases. This study investigates the neurotrophic potential of a polyphenolic-rich lemon peel extract (Lpe) in a Zebrafish larvae spinal cord injury (SCI) model. To evaluate its potential effects, embryos were divided into six experimental groups: a baseline control group in which larvae were neither subjected to spinal cord injury nor treated (Ctrl Group); a group with larvae subjected to spinal cord injury at 3 dpf without treatment (SCI Group); a group treated continuously with Lpe (25 \u00b5g\/mL) from 0 to 5 dpf without injury (Continuous Group); a group treated continuously with Lpe and injured at 3 dpf (Continuous SCI Group); a group treated with Lpe starting at 3 dpf without injury (Curative Group); and finally, a group injured at 3 dpf and treated simultaneously with Lpe (Curative SCI Group). Lpe treatment significantly downregulated proinflammatory cytokines (tnfa, il1b, and xcl8), and modulated the neuroregenerative pathways Wnt\/\u03b2 catenin, and neurotrophic factor Bdnf. Immunohistochemical analysis further revealed Sox2-positive cells localized around the central canal, consistent with activation of ependymal progenitor populations involved in injury-induced repair processes. These findings support the exploration of Lpe for mitigating SCI-induced damage.<\/jats:p>","DOI":"10.3390\/ijms27031201","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:14:23Z","timestamp":1769415263000},"page":"1201","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluation of Polyphenol-Rich Lemon Peel Extract Use in a Zebrafish Model of Spinal Cord Injury: Morphology, Repair-Associated Markers, and Inflammatory Profile"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-0442","authenticated-orcid":false,"given":"Mirea","family":"Sicari","sequence":"first","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Pansera","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9432-4588","authenticated-orcid":false,"given":"Kamel","family":"Mhalhel","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5551-9326","authenticated-orcid":false,"given":"Marialuisa","family":"Aragona","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariarosaria","family":"Galeano","sequence":"additional","affiliation":[{"name":"Department of Human Pathology and Evolutive Age \u201cGaetano Barresi\u201d, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele Rosario","family":"Colonna","sequence":"additional","affiliation":[{"name":"Department of Human Pathology and Evolutive Age \u201cGaetano Barresi\u201d, University of Messina, Via C. Valeria, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Levanti","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6847-880X","authenticated-orcid":false,"given":"Rosaria","family":"Laur\u00e0","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8399-5941","authenticated-orcid":false,"given":"Francesco","family":"Abbate","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0934-3619","authenticated-orcid":false,"given":"Antonino","family":"German\u00e0","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8195-4986","authenticated-orcid":false,"given":"Giuseppe","family":"Montalbano","sequence":"additional","affiliation":[{"name":"Zebrafish Neuromorphology Lab, Department of Veterinary Sciences, University of Messina, Polo Universitario dell\u2019 Annunziata, 98168 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1546-5098(10)02902-X","article-title":"Organization and Physiology of the Zebrafish Nervous System","volume":"Volume 29","author":"Vernier","year":"2010","journal-title":"Fish Physiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1002\/dvdy.77","article-title":"Evolution of Vertebrate Spinal Cord Patterning","volume":"248","author":"Leung","year":"2019","journal-title":"Dev. 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