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Brain microvascular endothelial cells are critical to maintain homeostasis between central nervous system and periphery. Resveratrol protects against ischemic stroke. 3,3\u2032,4,5\u2032\u2010tetramethoxy\u2010<jats:italic>trans<\/jats:italic>\u2010stilbene (3,3\u2032,4,5\u2032\u2010TMS) and 3,4\u2032,5\u2010trimethoxy\u2010<jats:italic>trans<\/jats:italic>\u2010stilbene (3,4\u2032,5\u2010TMS) are resveratrol derivatives with addition of methoxy groups, showing better pharmacokinetic performance. We aimed to explore their protective effects and underlying mechanisms. Oxygen\u2013glucose deprivation (OGD) model was applied in bEnd.3 cell line, mouse brain microvascular endothelium to mimic ischemia. The cells were pre\u2010treated with 3,3\u2032,4,5\u2032\u2010TMS or 3,4\u2032,5\u2010TMS (1 and 5\u2009\u03bcM, 24\u2009h) and then subjected to 2\u2010h OGD injury. Cell viability, levels of proinflammatory cytokines and reactive oxygen species (ROS), and protein expressions were measured by molecular assays and fluorescence staining. OGD injury triggered cell death, inflammatory responses, ROS production and nuclear factor\u2010kappa B (NF\u2010\u03baB) signalling pathway. These impairments were remarkably attenuated by the two stilbenes, 3,3\u2032,4,5\u2032\u2010TMS and 3,4\u2032,5\u2010TMS. They also alleviated endothelial barrier injuries through upregulating the expression of tight junction proteins. Moreover, 3,3\u2032,4,5\u2032\u2010TMS and 3,4\u2032,5\u2010TMS activated 5\u2032 adenosine monophosphate\u2010activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS). Overall, 3,3\u2032,4,5\u2032\u2010TMS and 3,4\u2032,5\u2010TMS exert protective effects against OGD damage through suppressing cell death, inflammatory responses, oxidative stress, as well as BBB disruption on bEnd.3 cells.<\/jats:p>","DOI":"10.1111\/jcmm.70008","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T16:29:25Z","timestamp":1723912165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["3,3\u2032,4,5\u2032\u2010Tetramethoxy\u2010trans\u2010stilbene and 3,4\u2032,5\u2010trimethoxy\u2010trans\u2010stilbene prevent oxygen\u2013glucose deprivation\u2010induced injury in brain endothelial cell"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6944-1830","authenticated-orcid":false,"given":"Chunxiu","family":"Zhou","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Teng","family":"Vong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau  Macau SAR China"},{"name":"Macau Centre for Research and Development in Chinese Medicine University of Macau  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haroon","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Abdul Wali Khan University Mardan  Mardan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1152-7997","authenticated-orcid":false,"given":"Wai San","family":"Cheang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences, University of Macau  Macau SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01828-z"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107695"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.10.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-020-00230-3"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308427"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190062"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05735.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4103\/0256-4947.83217"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.29"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-016-0398-4"},{"key":"e_1_2_10_12_1","first-page":"35","article-title":"The therapeutic potential of resveratrol: a review of clinical trials. 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