{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:31:12Z","timestamp":1791639072678,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770925"],"award-info":[{"award-number":["81770925"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81790641"],"award-info":[{"award-number":["81790641"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Outstanding academic leaders in Shanghai","award":["20XD1401100"],"award-info":[{"award-number":["20XD1401100"]}]},{"name":"Program for Outstanding Medical Academic Leader","award":["2019LJ01"],"award-info":[{"award-number":["2019LJ01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Increasing evidence indicates that nobiletin (NOB) is a promising neuroprotective agent. Astrocyte activation plays a key role in neurodegenerative disorders. Thus, this study aims to investigate the effects of NOB on astrocyte activation and the potential mechanisms. In this study, astrocytes were exposed to hypoxia injury for 24 h to induce activation in vitro. Glial fibrillary acidic protein (GFAP) was chosen as a marker of astrocyte activation. To evaluate the effects of NOB on the migration of activated astrocytes, we used a scratch wound healing assay and Transwell migration assay. In addition, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential, Nrf2 and HO-1 were measured to investigate the mechanisms of NOB in the activation of astrocytes. We found that NOB alleviated astrocyte activation and decreased GFAP expression during hypoxia. Simultaneously, NOB alleviated the migration of astrocytes induced by hypoxia. With NOB treatment, hypoxia-induced oxidative stress was partially reversed, including reducing the production of ROS and MDA. Furthermore, NOB significantly improved the mitochondrial dysfunction in activated astrocytes. Finally, NOB promoted Nrf2 nuclear translocation and HO-1 expression in response to continuous oxidative damage. Our study indicates, for the first time, that NOB alleviates the activation of astrocytes induced by hypoxia in vitro, in part by ameliorating oxidative stress and mitochondrial dysfunction. This provides new insights into the neuroprotective effects of NOB.<\/jats:p>","DOI":"10.3390\/molecules27061962","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:34:27Z","timestamp":1647812067000},"page":"1962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Nobiletin Alleviates Astrocyte Activation and Oxidative Stress Induced by Hypoxia In Vitro"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6922-6644","authenticated-orcid":false,"given":"Dandan","family":"Wang","sequence":"first","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200030, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200030, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200030, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai 200030, China"},{"name":"Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Shanghai 200030, China"},{"name":"Key Laboratory of Myopia, Ministry of Health, Shanghai 200030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100840","DOI":"10.1016\/j.preteyeres.2020.100840","article-title":"A neuroglia-based interpretation of glaucomatous neuroretinal rim thinning in the optic nerve head","volume":"77","author":"Lee","year":"2020","journal-title":"Prog. 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