Congrong San alleviates hippocampal neuronal injury and ferroptosis in AD rats by inhibiting GRP78-PERK-ATF4 signaling pathway
- VernacularTitle:苁蓉散通过抑制GRP78-PERK-ATF4信号通路减轻阿尔茨海默病大鼠海马神经元损伤和铁死亡
- Author:
Yuan-qin CAI
1
;
Xian-bing CHEN
;
Qing-hua LONG
;
Xi WANG
;
Zhen-ning WANG
;
Chu-hua ZENG
Author Information
- Publication Type:Journal Article
- Keywords: Congrong San; Alzheimer's disease; GRP78-PERK-ATF4; GPX4; hippocampus; ferropto-sis
- From: Chinese Pharmacological Bulletin 2025;41(5):874-880
- CountryChina
- Language:Chinese
- Abstract: Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.
