{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:22:51Z","timestamp":1786116171987,"version":"build-2736575974"},"reference-count":64,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neurodegenerative diseases represent a significant clinical challenge. Understanding the pathogenic mechanisms is essential for developing more effective therapies, and mitochondria appear to play a key role in these processes. Since current treatments are limited to symptom management, natural strategies capable of preserving mitochondrial function could represent a promising preventive and therapeutic approach in neurodegeneration. This study aims at investigating the molecular mechanisms underlying the neuroprotective potential of an anthocyanin-rich extract from Callistemon citrinus flower (Cce) in differentiated SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA). Exposure of cells to 6-OHDA inhibited cell viability and caused cell death, events hindered by the pre-treatment with Cce. Furthermore, it restored normal cell cycle distribution, as well as hampered 6-OHDA-induced apoptosis. Given the pro-oxidant effect of 6-OHDA, we observed that Cce reduced reactive oxygen species in stressed SH-SY5Y cells, along with recovering their antioxidant protection system. Focusing on mitochondria, Cce was able to protect their membranes from 6-OHDA, as suggested by the restoration of mitochondrial membrane potential. This led to a reduction in release of cytochrome c and the consequent activation of caspases 9 and 3, characteristic of the intrinsic apoptotic pathway, supporting our initial findings. Our results indicate that Cce prevents SH-SY5Y cell death induced by 6-OHDA via the preservation of mitochondrial integrity mainly through to its antioxidant properties, encouraging further studies to support its exploitation in the management of neurodegeneration.<\/jats:p>","DOI":"10.3390\/biom16081144","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T08:08:02Z","timestamp":1786003682000},"page":"1144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial Membrane Damage Is Prevented by an Anthocyanin-Rich Fraction of Callistemon citrinus in 6-OHDA-Exposed SH-SY5Y Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Martina","family":"Farina","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0792-5895","authenticated-orcid":false,"given":"Giuseppe Tancredi","family":"Patan\u00e8","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"},{"name":"\u201cProf. Antonio Imbesi\u201d Foundation, University of Messina, 98100 Messina, Italy"},{"name":"Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Putaggio","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-3392","authenticated-orcid":false,"given":"Ester","family":"Tellone","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-4069","authenticated-orcid":false,"given":"Davide","family":"Barreca","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-3123","authenticated-orcid":false,"given":"Alessandro","family":"Maugeri","sequence":"additional","affiliation":[{"name":"Department of Veterinary Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-7820","authenticated-orcid":false,"given":"Michele","family":"Navarra","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98168 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,6]]},"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":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal trends in the prevalence of Parkinson\u2019s disease from 1980 to 2023: A systematic review and meta-analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Healthy Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/S0140-6736(23)01419-8","article-title":"The epidemiology of Parkinson\u2019s disease","volume":"403","author":"Darweesh","year":"2024","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Luo, Y., Qiao, L., Li, M., Wen, X., Zhang, W., and Li, X. 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