{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:38:06Z","timestamp":1788925086299,"version":"build-2803163510"},"reference-count":68,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation of China","award":["81960240"],"award-info":[{"award-number":["81960240"]}]},{"name":"National Science Foundation of China","award":["202001AY070001-001"],"award-info":[{"award-number":["202001AY070001-001"]}]},{"name":"National Science Foundation of China","award":["2023Y0782"],"award-info":[{"award-number":["2023Y0782"]}]},{"name":"National Science Foundation of China","award":["2024XKTDPY16"],"award-info":[{"award-number":["2024XKTDPY16"]}]},{"name":"Yunnan Applied Basic Research\u2014Yunnan Provincial Science and Technology Department\u2014Kunming Medical University","award":["81960240"],"award-info":[{"award-number":["81960240"]}]},{"name":"Yunnan Applied Basic Research\u2014Yunnan Provincial Science and Technology Department\u2014Kunming Medical University","award":["202001AY070001-001"],"award-info":[{"award-number":["202001AY070001-001"]}]},{"name":"Yunnan Applied Basic Research\u2014Yunnan Provincial Science and Technology Department\u2014Kunming Medical University","award":["2023Y0782"],"award-info":[{"award-number":["2023Y0782"]}]},{"name":"Yunnan Applied Basic Research\u2014Yunnan Provincial Science and Technology Department\u2014Kunming Medical University","award":["2024XKTDPY16"],"award-info":[{"award-number":["2024XKTDPY16"]}]},{"name":"Scientific Research Fund of Education Department of Yunnan Province","award":["81960240"],"award-info":[{"award-number":["81960240"]}]},{"name":"Scientific Research Fund of Education Department of Yunnan Province","award":["202001AY070001-001"],"award-info":[{"award-number":["202001AY070001-001"]}]},{"name":"Scientific Research Fund of Education Department of Yunnan Province","award":["2023Y0782"],"award-info":[{"award-number":["2023Y0782"]}]},{"name":"Scientific Research Fund of Education Department of Yunnan Province","award":["2024XKTDPY16"],"award-info":[{"award-number":["2024XKTDPY16"]}]},{"name":"First-Class Discipline Team of Kunming Medical University","award":["81960240"],"award-info":[{"award-number":["81960240"]}]},{"name":"First-Class Discipline Team of Kunming Medical University","award":["202001AY070001-001"],"award-info":[{"award-number":["202001AY070001-001"]}]},{"name":"First-Class Discipline Team of Kunming Medical University","award":["2023Y0782"],"award-info":[{"award-number":["2023Y0782"]}]},{"name":"First-Class Discipline Team of Kunming Medical University","award":["2024XKTDPY16"],"award-info":[{"award-number":["2024XKTDPY16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The occurrence of demyelination in the central nervous system (CNS) causes neurodegenerative lesions. The occurrence and development of demyelination involve multiple pathological mechanisms, including the generation of reactive oxygen species (ROS) caused by mitochondrial dysfunction in microglia and subsequent neuroinflammation. Scutellarin is a natural flavonoid drug with significant neuroprotective effects, including antioxidant, anti-inflammatory, and anti-apoptotic properties, and is widely used in the treatment of neurological diseases. However, the protective effects and mechanisms of scutellarin on demyelination have not yet been elucidated. This study aims to investigate the neuroprotective effects of scutellarin on demyelination and its underlying molecular mechanisms. Our results showed that treatment with scutellarin significantly alleviated Cuprizone-induced myelin damage, neuronal apoptosis, and neurological deficits in mice. In in vitro experiments, scutellarin significantly reduced Cuprizone\u2013copper-induced pro-inflammatory microglia formation and inhibited the secretion of TNF-\u03b1, thereby reducing myelin cell damage. Mechanism studies revealed that scutellarin inhibited the secretion of TNF-\u03b1 by microglia and alleviated myelin cell damage by reducing the excessive production of mitochondrial reactive oxygen species (Mito-ROS), reactive oxygen species (ROS), and malondialdehyde (MDA) induced by Cuprizone\u2013copper in microglia. Finally, scutellarin improved mitochondrial dysfunction in microglia and significantly alleviated myelin cell damage by inhibiting the expression of p38MAPK. In conclusion, our findings demonstrate that scutellarin exerts significant neuroprotective effects on Cuprizone-induced mice by improving mitochondrial dysfunction in microglia, thereby reducing inflammatory responses. This effect is closely associated with the inhibition of the p38MAPK pathway.<\/jats:p>","DOI":"10.3390\/antiox14060723","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T03:53:12Z","timestamp":1749786792000},"page":"723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Scutellarin Alleviates Cuprizone-Induced Demyelination by Improving Mitochondrial Dysfunction, Reducing Lipid Oxidation and Inhibiting the p38 MAPK Pathway"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7639-614X","authenticated-orcid":false,"given":"Qiting","family":"Zhao","sequence":"first","affiliation":[{"name":"Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yantuanjin","family":"Ma","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufen","family":"Wang","sequence":"additional","affiliation":[{"name":"Yunnan Key Laboratory of Breast Cancer Precision Medicine, Academy of Biomedical Engineering, Kunming Medical University, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/s41593-021-00917-2","article-title":"Periods of synchronized myelin changes shape brain function and plasticity","volume":"24","author":"Pivonkova","year":"2021","journal-title":"Nat. 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