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We stimulated cells with homocysteine (1\u00a0mmol\/L, 24\u00a0hours) and tested the effects of gastrodin (200\u2010800\u00a0\u03bcg\/mL) on cell viability and the production of malondialdehyde (MDA), lactate dehydrogenase (LDH) and reactive oxygen species (ROS). Then, Nrf2 distribution in the cytoplasm and nucleus as well as the expression of enzymes downstream of Nrf2 was determined. Furthermore, we analysed the expression of bax, bcl\u20102 and cleaved caspase3, and assessed the involvement of the PI3K\/Akt\/eNOS pathway by Western blots. Finally, we tested the vasoactive effect of gastrodin in thoracic aortic rings. The results showed that gastrodin decreased MDA, LDH and ROS production and increased cell viability, NO production and relaxation of thoracic aortic rings. Moreover, the protective effects of Gas on NO production and relaxation of thoracic aortic rings were blocked by L\u2010NAME but enhanced by Cav\u20101 knockdown, and MK\u20102206 treatment abolished the effect of Gas on the ROS. In addition, treatment with gastrodin increased Nrf2 nuclear translocation, thus enhancing the expression of downstream enzymes. Finally, gastrodin increased the expression of PI3K, p\u2010Akt, and eNOS and decreased Cav\u20101 protein expression. In conclusion, our study suggested that gastrodin may protect HUVECs from homocysteine\u2010induced injury, and the PI3K\/Akt\/eNOS and Nrf2\/ARE pathways may be responsible for the efficacy of gastrodin.<\/jats:p>","DOI":"10.1111\/jcmm.16073","type":"journal-article","created":{"date-parts":[[2020,12,16]],"date-time":"2020-12-16T00:32:20Z","timestamp":1608078740000},"page":"345-357","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Gastrodin prevents homocysteine\u2010induced human umbilical vein endothelial cells injury via PI3K\/Akt\/eNOS and Nrf2\/ARE pathway"],"prefix":"10.1111","volume":"25","author":[{"given":"Jiyu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Life Science and Technology China Pharmaceutical University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Life 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