PMID- 35380368 OWN - NLM STAT- MEDLINE DCOM- 20220426 LR - 20220426 IS - 1476-3524 (Electronic) IS - 1029-8428 (Linking) VI - 40 IP - 2 DP - 2022 Apr TI - Crocin Alleviates Intracerebral Hemorrhage-Induced Neuronal Ferroptosis by Facilitating Nrf2 Nuclear Translocation. PG - 596-604 LID - 10.1007/s12640-022-00500-y [doi] AB - Intracerebral hemorrhage (ICH) is the deadliest type of stroke. Oxidative stress was considered to play an important role in ICH-induced secondary injury. Crocin, the main compound isolated from Crocus sativus L., possesses a potential anti-oxidative function in many types of diseases including ICH. In the current study, the protective role of crocin in ICH-induced brain injury was investigated in the ICH model. The ICH-induced brain edema and neurological deficits were analyzed by brain edema measurement and neurological testing. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity and the content of malondialdehyde (MDA) were assessed by a total superoxide dismutase assay kit. The expressions of ferroptosis-related genes were verified by quantitative real-time PCR (qPCR) and western blotting. The ICH-induced brain edema and neurological deficits were significantly decreased after treatment with crocin. Moreover, the SOD and GSH-px activities were obviously increased in the ICH with crocin-treated group compared with the ICH group, while the content of MDA was markedly decreased after treatment with crocin. Crocin inhibited ferroptosis of neuron cells, as evidenced by increased Fe(2+) concentration and the expression of GPX4, FTH1, and SLC7A11. Mechanistically, crocin treatment increased the expression and nuclear translocation of Nrf2. Our data suggest that crocin alleviates intracerebral hemorrhage-induced neuronal ferroptosis by facilitating Nrf2 nuclear translocation. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Wang, Fei AU - Wang F AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - Li, Wu-Lin AU - Li WL AD - Department of Emergency, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - Shen, Li-Juan AU - Shen LJ AD - Department of Central Laboratory, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China. AD - Clinical Trials Unit, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China. FAU - Jiang, Ting-Ting AU - Jiang TT AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - Xia, Jian-Jun AU - Xia JJ AD - Department of Emergency, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - You, Da-Li AU - You DL AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - Hu, Shan-You AU - Hu SY AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. FAU - Wang, Li AU - Wang L AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. wangli@189.cn. AD - Department of Central Laboratory, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, China. wangli@189.cn. FAU - Wu, Xiao AU - Wu X AUID- ORCID: 0000-0002-9998-8084 AD - Department of Critical Care Medicine, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. wx5187@163.com. AD - Department of Emergency, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, No. 1, Chengbei Rd, Jiading District, Shanghai, China. wx5187@163.com. LA - eng GR - 19ZR1444900/Natural Science Foundation of Shanghai/ GR - SSF-21-16-001/Scientific Research Foundation of Shanghai University of Medicine & Health Sciences/ GR - 2018-KY-06/Shanghai Municipal Jiading District Health Commission Foundation/ PT - Journal Article DEP - 20220405 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Antioxidants) RN - 0 (NF-E2-Related Factor 2) RN - 36-88-4 (Carotenoids) RN - 877GWI46C2 (crocin) RN - EC 1.15.1.1 (Superoxide Dismutase) SB - IM MH - Antioxidants/pharmacology MH - *Brain Edema/drug therapy/etiology/metabolism MH - *Brain Injuries/metabolism MH - Carotenoids MH - Cerebral Hemorrhage/drug therapy MH - *Ferroptosis MH - Humans MH - NF-E2-Related Factor 2/metabolism MH - Neurons/metabolism MH - Oxidative Stress MH - Superoxide Dismutase/metabolism OTO - NOTNLM OT - Crocin OT - Ferroptosis OT - Intracerebral hemorrhage OT - Nrf2 OT - Oxidative stress EDAT- 2022/04/06 06:00 MHDA- 2022/04/27 06:00 CRDT- 2022/04/05 12:07 PHST- 2022/01/05 00:00 [received] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/03/24 00:00 [revised] PHST- 2022/04/06 06:00 [pubmed] PHST- 2022/04/27 06:00 [medline] PHST- 2022/04/05 12:07 [entrez] AID - 10.1007/s12640-022-00500-y [pii] AID - 10.1007/s12640-022-00500-y [doi] PST - ppublish SO - Neurotox Res. 2022 Apr;40(2):596-604. doi: 10.1007/s12640-022-00500-y. Epub 2022 Apr 5.