Effects of nuciferine on neuroinflammation and ferroptosis in mice with chronic hypoperfusion-induced white matter injury
- VernacularTitle:荷叶碱对慢性低灌注脑白质损伤小鼠神经炎症和铁死亡的影响
- Author:
Ting-ting DUAN
1
;
Gui-min JIN
;
Yuan-yuan ZHU
;
Yu-hao XU
;
Yue-feng LI
;
Chen QIAO
;
Ming YU
Author Information
- Publication Type:Journal Article
- Keywords: nuciferine; chronic cerebral hypoperfu-sion; neuroinflammation; ferroptosis; PI3K/Akt signa-ling pathway; NRF2/xCT/GPX4 signaling pathway
- From: Chinese Pharmacological Bulletin 2025;41(10):1931-1940
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the effects of nuciferine on cognitive behavior and the underlying mechanisms,white matter injury(WMI),neuroinflammation,and ferroptosis in mice with chronic ischemic WMI.Meth-ods Sixty C57BL/6 mice were divided into a control group,a bilateral common carotid artery stenosis(BCAS)model group,and low/high-dose nuciferine groups(20/40 mg·kg-1).A chronic ischemic WMI model was established using BCAS surgery.Following eight weeks of treatment,cognitive behavior(Y-maze,novel object recognition,Morris water maze),white matter integrity(LFB/MBP staining),microglial acti-vation(Iba-1 immunofluorescence),inflammatory cy-tokines(ELISA for TNF-α,IL-1β,IL-6),ferroptosis markers(Fe2+,ROS,MDA,GSH),mitochondrial ultrastructure(electron microscopy),and protein ex-pression of the PI3K/Akt and NRF2/xCT/GPX4 signa-ling pathways(Western blot)were evaluated.Results Compared with the control group,the BCAS group showed significant cognitive decline(P＜0.05),re-duced myelin density,elevated inflammatory cytokines and ferroptosis markers(Fe2+,ROS,MDA),shrunk-en mitochondria,and downregulated PI3K/Akt and NRF2/xCT/GPX4 pathway proteins(P＜0.05).Nu-ciferine intervention significantly ameliorated these in-juries in BCAS mice,with the high-dose group exhibi-ting superior effects(P＜0.05).Conclusions Nu-ciferine exerts protective effects against chronic ische-mic WMI and cognitive impairment by activating the PI3K/Akt and NRF2/xCT/GPX4 signaling pathways,thereby suppressing neuroinflammation and ferroptosis.
