{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T05:56:42Z","timestamp":1770530202185,"version":"3.49.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Isoliensinine (ISO), a natural compound, is a bibenzyl isoquinoline alkaloid monomer in lotus seed, which has strong antioxidant and free radical scavenging activities. The oxidative toxicity caused by glutamic acid overdose is one of the important mechanisms of nerve cell injury, and the oxidative toxicity caused by glutamic acid is related to ferroptosis. This study aims to establish a glutamate\u2010induced injury model of mouse hippocampal neurons HT\u201022 cells, and investigate the protective effect of ISO on the neurotoxicity of glutamate\u2010induced HT\u201022 cells. The results showed that ISO inhibited glutamate\u2010induced ferroptosis of neuronal cells through nuclear factor E2\u2010related factor 2\/glutathione peroxidase 4 (Nrf2\/GPX4) signaling pathway. Pretreatment of HT\u201022 cells with ISO significantly reduced glutamate\u2010induced cell death. Ferroptosis inhibitors have the same effect. ISO inhibited the decrease of mitochondrial membrane potential detection and the increase of iron content induced by glutamate, the increase of malondialdehyde and reactive oxygen species in cytoplasm and lipid, and protected the activities of GPx and superoxide dismutase enzymes. In addition, WB showed that glutamic acid could induce the upregulated expression of long\u2010chain esteryl coA synthase 4 (ACSL4) protein and the downregulated expression of SLC7A11 and GPX4 protein in HT\u201022 cells, while ISO could prevent the abnormal expression of these proteins induced by glutamic acid. The nuclear translocation of Nrf2 in HT\u201022 cells was increased, and the expression of downstream heme oxygenase\u20101 protein was upregulated. In summary, ISO protects HT\u201022 cells from glutamate\u2010induced ferroptosis through a novel mechanism of the Nrf2\/GPX4 signaling pathway.<\/jats:p>","DOI":"10.1002\/jbt.23794","type":"journal-article","created":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T01:21:26Z","timestamp":1724289686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Isoliensinine activated the Nrf2\/GPX4 pathway to inhibit glutamate\u2010induced ferroptosis in HT\u201022 cells"],"prefix":"10.1002","volume":"38","author":[{"given":"Hui\u2010Zhi","family":"Long","sequence":"first","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Phase I Clinical Trial Centre, The Affiliated Changsha Central Hospital, Hengyang Medical School University of South China Changsha China"},{"name":"Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research School of Pharmacy of University of South China 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