Withaferin A inhibits ferroptosis and protects against intracerebral hemorrhage  

作　　者：Zi-Xian Zhou Qi Cui Ying-Mei Zhang Jia-Xin Yang Wen-Jing Xiang Ning Tian Yan-Lin Jiang Mei-Ling Chen Bin Yang Qing-Hua Li Ru-Jia Liao 

机构地区：[1]Laboratory of Neuroscience,Affiliated Hospital of Guilin Medical University,Guilin Medical University,Guilin,Guangxi Zhuang Autonomous Region,China [2]Department of Neurology,Affiliated Hospital of Guilin Medical University,Guilin Medical University,Guilin,Guangxi Zhuang Autonomous Region,China [3]Guangxi Clinical Research Center for Neurological Diseases,Affiliated Hospital of Guilin Medical University,Guilin Medical University,Guilin,Guangxi Zhuang Autonomous Region,China [4]Department of Pharmacology,Affiliated Hospital of Guilin Medical University,Guilin Medical University,Guilin,Guangxi Zhuang Autonomous Region,China

出　　处：《Neural Regeneration Research》2023年第6期1308-1315,共8页中国神经再生研究（英文版）

基　　金：supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region,No.2020GXNSFAA259036(to RJL);the Guangxi Science and Technology Project,No.Guike AD17129015(to QHL);Guangxi Research and Innovation Base for Basic and Clinical Application of Nerve Injury and Repair Project,No.Guike ZY21195042(to QHL);the Innovation Projects of Guangxi Graduate Education,Nos.YCSW2021246(to ZXZ),YCSW2021254(to WJX).

摘　　要：Recent studies have indicated that suppressing oxidative stress and ferroptosis can considerably improve the prognosis of intracerebral hemorrhage(ICH).Withaferin A(WFA),a natural compound,exhibits a positive effect on a number of neurological diseases.However,the effects of WFA on oxidative stress and ferroptosis-mediated signaling pathways to ICH remain unknown.In this study,we investigated the neuroprotective effects and underlying mechanism for WFA in the regulation of ICH-induced oxidative stress and ferroptosis.We established a mouse model of ICH by injection of autologous tail artery blood into the caudate nucleus and an in vitro cell model of hemin-induced ICH.WFA was injected intracerebroventricularly at 0.1,1 or 5μg/kg once daily for 7 days,starting immediately after ICH operation.WFA markedly reduced brain tissue injury and iron deposition and improved neurological function in a dose-dependent manner 7 days after cerebral hemorrhage.Through in vitro experiments,cell viability test showed that WFA protected SH-SY5Y neuronal cells against hemin-induced cell injury.Enzyme-linked immunosorbent assays in vitro and in vivo showed that WFA markedly decreased the level of malondialdehyde,an oxidative stress marker,and increased the activities of anti-oxidative stress markers superoxide dismutase and glutathione peroxidase after ICH.Western blot assay,quantitative polymerase chain reaction and immunofluorescence results demonstrated that WFA activated the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling axis,promoted translocation of Nrf2 from the cytoplasm to nucleus,and increased HO-1 expression.Silencing Nrf2 with siRNA completely reversed HO-1 expression,oxidative stress and protective effects of WFA.Furthermore,WFA reduced hemin-induced ferroptosis.However,after treatment with an HO-1 inhibitor,the neuroprotective effects of WFA against hemin-induced ferroptosis were weakened.MTT test results showed that WFA combined with ferrostatin-1 reduced hemin-induced SH-SY5Y neuronal cell in

关 键 词：behavior brain injuries hemorrhagic stroke ferroptosis heme oxygenase-1 NEUROPROTECTION nuclear factor E2-related factor 2 nuclear translocator oxidative stress STROKE 

分 类 号：R743.34[医药卫生—神经病学与精神病学]