{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:53:04Z","timestamp":1788274384107,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T00:00:00Z","timestamp":1587427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["106YGH-TMU-09"],"award-info":[{"award-number":["106YGH-TMU-09"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and Technology Grants","award":["MOST-102-2314-B-038-025-MY3, 108-2314-B-038-062"],"award-info":[{"award-number":["MOST-102-2314-B-038-025-MY3, 108-2314-B-038-062"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Background: Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the economy in our society. Current treatments, such as the use of thrombolytic agents, are often limited by a narrow therapeutic time window. However, the regeneration of the brain after damage is still active days, even weeks, after stroke occurs, which might provide a second window for treatment. Emodin, a traditional Chinese medicinal herb widely used to treat acute hepatitis, has been reported to possess antioxidative capabilities and protective effects against myocardial ischemia\/reperfusion injury. However, the underlying mechanisms and neuroprotective functions of Emodin in a rat middle cerebral artery occlusion (MCAO) model of ischemic stroke remain unknown. This study investigates neuroprotective effects of Emodin in ischemia both in vitro and in vivo. Methods: PC12 cells were exposed to oxygen-glucose deprivation to simulate hypoxic injury, and the involved signaling pathways and results of Emodin treatment were evaluated. The therapeutic effects of Emodin in ischemia animals were further investigated. Results: Emodin reduced infarct volume and cell death following focal cerebral ischemia injury. Emodin treatment restored PC12 cell viability and reduced reactive oxygen species (ROS) production and glutamate release under conditions of ischemia\/hypoxia. Emodin increased Bcl-2 and glutamate transporter-1 (GLT-l) expression but suppressed activated-caspase 3 levels through activating the extracellular signal-regulated kinase (ERK)-1\/2 signaling pathway. Conclusion: Emodin induced Bcl-2 and GLT-1 expression to inhibit neuronal apoptosis and ROS generation while reducing glutamate toxicity via the ERK-1\/2 signaling pathway. Furthermore, Emodin alleviated nerve cell injury following ischemia\/reperfusion in a rat MCAO model. Emodin has neuroprotective effects against ischemia\/reperfusion injury both in vitro and in vivo, which may be through activating the ERK-1\/2 signaling pathway.<\/jats:p>","DOI":"10.3390\/ijms21082899","type":"journal-article","created":{"date-parts":[[2020,4,22]],"date-time":"2020-04-22T04:15:13Z","timestamp":1587528913000},"page":"2899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Neuroprotective Effects of Emodin against Ischemia\/Reperfusion Injury through Activating ERK-1\/2 Signaling Pathway"],"prefix":"10.3390","volume":"21","author":[{"given":"Stephen Wan","family":"Leung","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Yuan\u2019s General Hospital, 162 Cheng Kung 1st Road, Kaohsiung 80249, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing Huei","family":"Lai","sequence":"additional","affiliation":[{"name":"Core Laboratory of Neuroscience, Office of R&amp;D, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Chung-Che","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Neurosurgery, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Rou","family":"Tsai","sequence":"additional","affiliation":[{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo-Jhen","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Hsiao","family":"Chiang","sequence":"additional","affiliation":[{"name":"Core Laboratory of Neuroscience, Office of R&amp;D, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Neurosurgery, Taipei Medical University Hospital, 252 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Fu","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Taipei City Hospital, Zhong Xiao Branch, 87 Tongde Rd., Nangang District, Taipei 11556, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Neurotrauma and Neuroregeneration, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"},{"name":"Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1177\/0004563216663775","article-title":"Haemostatic factors do not account for worse outcomes from ischaemic stroke in patients with higher C-reactive protein concentrations","volume":"54","author":"Slomka","year":"2017","journal-title":"Ann. 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