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Growing preclinical evidence indicates that PSO has anti\u2010inflammatory, anti\u2010vitiligo, anti\u2010bacterial, and anti\u2010viral effects. Growth arrest\u2010specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6\/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia\/reoxygenation (HR) injury via activating the GAS6\/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor\u2010related factor 2 (Nrf\u20102), NAD(P)H dehydrogenase quinone\u20101 (NQO1), heme oxygenase\u20101 (HO\u20101), silent information regulator 1 (SIRT1), peroxisome proliferator\u2010activated receptor coactivator 1\u03b1 (PGC\u20101\u03b1), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B\u2010cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR\u2010induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6\/Axl signaling.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7481","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T10:02:57Z","timestamp":1652868177000},"page":"2628-2640","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Psoralidin protects against cerebral hypoxia\/reoxygenation injury: Role of\n                    <scp>GAS6<\/scp>\n                    \/Axl signaling"],"prefix":"10.1002","volume":"36","author":[{"given":"Wangrui","family":"Lei","sequence":"first","affiliation":[{"name":"Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi'an No. 3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine Northwest University  Xi'an 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