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Gastrodin, the main active metabolite of <jats:italic>Gastrodia elata<\/jats:italic> Blume, used in Chinese medicine and food, has a wide range of pharmacological effects, mostly related to CNS disorders. This review aims to systematically summarize and discuss the effects and underlying mechanisms of gastrodin in the treatment of CNS diseases, and to assess its potential for further development as a lead drug in both biomedicine and traditional Chinese medicine. Studies on the pharmacological effects of gastrodin on the CNS indicate that it may exert anti\u2010neurodegenerative, cerebrovascular protective, and ameliorative effects on diabetic encephalopathy, perioperative neurocognitive dysfunction, epilepsy, Tourette's syndrome, depression and anxiety, and sleep disorders through various mechanisms. To date, 110 gastrodin products have been approved for clinical use, but further multicenter clinical case\u2013control studies are relatively scarce. Preclinical studies have confirmed that gastrodin can be used to treat CNS\u2010related disorders. However, important concerns need to be addressed in the context of likely non\u2010specific, assay interfering effects when gastrodin is studied using in vitro and in silico approaches, calling for a systematic assessment of the evidence to date. High\u2010quality clinical trials should have priority to evaluate the therapeutic safety and clinical efficacy of gastrodin. Further experimental research using appropriate in vivo models is also needed, focusing on neurodegenerative diseases, cerebral ischemic and hypoxic diseases, brain damage caused by methamphetamine or heavy metals, and epilepsy.<\/jats:p>","DOI":"10.1002\/ptr.8314","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T06:49:10Z","timestamp":1723790950000},"page":"5107-5133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The role of gastrodin in the management of CNS\u2010related diseases: Underlying mechanisms to therapeutic perspectives"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0287-3828","authenticated-orcid":false,"given":"Xirui","family":"He","sequence":"first","affiliation":[{"name":"School of Bioengineering, Zhuhai Campus Zunyi Medical University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufei","family":"Chen","sequence":"additional","affiliation":[{"name":"Key laboratory of Western Resource Biology and Modern Biotechnology Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Bioengineering, Zhuhai Campus Zunyi Medical University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1055-4299","authenticated-orcid":false,"given":"Jingyi","family":"Gu","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, Pharmacognosy &amp; Phytotherapy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Bioengineering, Zhuhai Campus Zunyi Medical University  Zhuhai China"},{"name":"College of Pharmaceutical Sciences Southwest University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Bioengineering, Zhuhai Campus Zunyi Medical University  Zhuhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Hao","sequence":"additional","affiliation":[{"name":"Clinical Medical College of Acupuncture Moxibustion and Rehabilitation Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Ortho\u2010 and MSK\u2010Science University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2611-6303","authenticated-orcid":false,"given":"Michael","family":"Heinrich","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy, Pharmacognosy &amp; Phytotherapy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0254-9026.2021.04.001"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1005-9202.2024.07.042"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14071417"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202667"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155369"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.06.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.01239"},{"issue":"6","key":"e_1_2_11_9_1","first-page":"771","article-title":"Clinical observation of Gastrodin injection in combination with oxcarbazepine in the treatment of secondary epilepsy after cerebral infarction","volume":"36","author":"Deng J. 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