Improvement effects and mechanism of Zhichi suanzaoren decoction on oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice
- VernacularTitle:栀豉酸枣仁汤对围绝经期失眠小鼠海马神经元氧化应激损伤的改善作用及机制
- Author:
Yufei LIU
1
;
Zeyu ZHANG
1
;
Yonghua ZHANG
2
;
Linlin HU
2
;
Xin ZHANG
1
Author Information
1. School of Pharmaceutical Sciences，Zhejiang Chinese Medical University，Hangzhou 311402，China
2. Sleep Medicine Center，Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University，Hangzhou 310007，China
- Publication Type:Journal Article
- Keywords:
Zhichi suanzaoren decoction;
perimenopausal insomnia;
hippocampal neurons;
genomics;
oxidative stress
- From:
China Pharmacy
2025;36(19):2372-2378
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the improvement effects and mechanism of Zhichi suanzaoren decoction （ZSD） on hippocampal oxidative stress injury in hippocampal neurons of mice with perimenopausal insomnia. METHODS The potential targets of active ingredients in ZSD were predicted using TCMSP and TCMIP databases； the targets related to insomnia were searched through GeneCards， OMIM and DisGeNET databases； protein-protein interaction network of intersecting targets of ZSD ingredients and insomnia was constructed； Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted on key targets. Sixty mice were divided into sham operation group， model group， ZSD low-， medium-， and high-dose groups （11， 22， and 33 g/kg）， and eszopiclone group （positive control， 1 mg/kg）. Except for sham operation group， the perimenopausal insomnia model was constructed by ovariectomy （OVX） in the other groups. After successful modeling， mice in each group were gavaged with normal saline or the corresponding drug solution， once a day， for three consecutive weeks. The sleep status of mice was evaluated through the pentobarbital sodium sleep synergy experiment， and the pathological changes of hippocampal neurons and the expressions of related genes and proteins in mice were observed by HE staining， immunohistochemistry staining， immunofluorescence staining， transcriptome sequencing technology and Western blot. RESULTS The results of network pharmacology showed that there were 296 intersection targets between ZSD and perimenopausal insomnia. Protein kinase B1 （Akt1） was a key target for treating insomnia with ZSD. After administration of ZSD， the sleep latency of mice was shortened， the sleep duration was prolonged significantly， and the mean optical density value of neuron-specific nuclear protein in the hippocampal CA1 region was significantly increased （P＜0.01）. Additionally， hippocampal neuron damage in OVX mice was significantly alleviated. The results of transcriptome sequencing showed that ZSD significantly upregulated the transcriptional levels of Nfe2l2 gene in hippocampal tissue of OVX mice （P＜0.05）. After administration of ZSD， protein expressions of nuclear factor E2 related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in hippocampal tissue of OVX mice， as well as the phosphorylated Akt level， were increased significantly （P＜0.01）. CONCLUSIONS ZSD can ameliorate hippocampal oxidative stress injury of hippocampal neurons in perimenopausal insomnia mice by activating the Akt/Nrf2/HO-1 signaling pathway.
