{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:08:58Z","timestamp":1778476138357,"version":"3.51.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal cord ischemia-reperfusion injury (SCIRI) remains a major clinical challenge with few effective treatments. Ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation, plays a key role in SCIRI pathology, and activation of the Nrf2\/HO-1 pathway can counteract this process. Bitter gourd bioactive peptide (BGBP) is a natural low-molecular-weight peptide with antioxidant properties, but its effect on SCIRI induced ferroptosis is unknown. This study aimed to determine whether BGBP protects against SCIRI by inhibiting neuronal ferroptosis via the Nrf2\/HO-1 pathway, using two emerging cell and animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An\n                      <jats:italic>in vitro<\/jats:italic>\n                      chemical hypoxia model was established in BV-2 microglial cells using CoCl\n                      <jats:sub>2<\/jats:sub>\n                      , which mimics hypoxic injury without the need for specialized chambers. An\n                      <jats:italic>in vivo<\/jats:italic>\n                      rat SCIRI model was created by transient abdominal aortic clamping, a reproducible method that preserves partial spinal cord blood supply. BGBP was applied at its optimal concentration (1.6 mg\/mL\n                      <jats:italic>in vitro<\/jats:italic>\n                      ; 50 mg\/kg orally\n                      <jats:italic>in vivo<\/jats:italic>\n                      ). We assessed cell viability, oxidative stress markers (ROS, MDA, SOD), ferroptosis indicators (Fe\n                      <jats:sup>2+<\/jats:sup>\n                      , GSH, GPX4), apoptosis-related proteins (Bcl-2, Bax, Cleaved-Caspase-3), and Nrf2\/HO-1 pathway activation by qPCR and western blot. Motor function was evaluated using Tarlov and BBB scores, and spinal cord histopathology was examined by H&amp;amp;E and Nissl staining.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and conclusion<\/jats:title>\n                    <jats:p>\n                      BGBP significantly improved BV-2 cell viability under CoCl\n                      <jats:sub>2<\/jats:sub>\n                      induced hypoxia and reduced ROS, MDA, and Fe\n                      <jats:sup>2+<\/jats:sup>\n                      levels while restoring SOD, GSH, and GPX4 activities. It also rebalanced the Bcl-2\/Bax ratio and suppressed Cleaved-Caspase-3. Both mRNA and protein levels of Nrf2 and HO-1 were upregulated by BGBP. In the rat SCIRI model, BGBP treatment improved hindlimb motor scores, preserved motor neuron morphology, and reduced histopathological damage, consistent with the\n                      <jats:italic>in vitro<\/jats:italic>\n                      findings. BGBP attenuates neuronal ferroptosis and oxidative stress after SCIRI by activating the Nrf2\/HO-1 pathway. The combination of the CoCl\n                      <jats:sub>2<\/jats:sub>\n                      induced BV-2 cell model and the rat abdominal aortic clamping model offers a robust and practical methodological platform for studying ferroptosis-targeted neuroprotection.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1850363","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:24:45Z","timestamp":1778473485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bitter gourd bioactive peptide alleviates neuronal ferroptosis after spinal cord ischemia-reperfusion injury, combined with emerging cell and animal models"],"prefix":"10.3389","volume":"13","author":[{"given":"Qiyang","family":"Diao","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Peking University Cancer Hospital (Inner Mongolia Campus)\/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Nuo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Inner Mongolia Autonomous Region People\u2019s Hospital","place":["Hohhot, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qimuge","family":"Suyila","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Center of the Affiliated Hospital, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongzhen","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Peking University Cancer Hospital (Inner Mongolia Campus)\/Affiliated Cancer Hospital of Inner Mongolia Medical University, Inner Mongolia Medical University","place":["Hohhot, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiulan","family":"Su","sequence":"additional","affiliation":[{"name":"Clinical Medical Research Center of Affiliated Hospital, Inner Mongolia Medical University, Inner Mongolia Bioactive Peptide Engineering Laboratory","place":["Hohhot, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1590493","DOI":"10.3389\/fncel.2025.1590493","article-title":"The role of oxidative stress in spinal cord ischemia reperfusion injury: mechanisms and therapeutic implications.","volume":"19","author":"Xing","year":"2025","journal-title":"Front Cell Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"110278","DOI":"10.1016\/j.jneumeth.2024.110278","article-title":"Strategies for the development of in vitro models of spinal cord ischemia-reperfusion injury: oxygen-glucose deprivation and reoxygenation.","volume":"412","author":"Lee","year":"2024","journal-title":"J Neurosci Methods."},{"key":"B3","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s11064-022-03794-8","article-title":"Rodent models of spinal cord injury: from pathology to application.","volume":"48","author":"Liu","year":"2023","journal-title":"Neurochem Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1186\/s12964-025-02459-7","article-title":"Challenges in mimicking hypoxia: insights into HIF-regulated MiRNA expression induced by DMOG and CoCl2.","volume":"23","author":"Barton","year":"2025","journal-title":"Cell Commun Signal."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1002\/ar.23694","article-title":"Arterial blood supply to the spinal cord in animal models of spinal cord injury. 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