Zhichi Suanzaoren Decoction, a traditional Chinese medicine, alleviates insomnia and anxiety by restoring hippocampal astrocyte cilia through Foxj1 upregulation.
The primary components of Zhichi Suanzaoren Decoction were analyzed in both positive and negative ion modes using Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight/Mass Spectrometry. A perimenopausal insomnia model was established through bilateral ovariectomy in mice, which was then treated with the decoction. The team conducted behavioral tests and sleep synergy experiments to assess the anti-insomnia and anxiolytic effects of the decoction. Further, to investigate the mechanistic details, techniques such as ELISA, Nissl staining, immunohistochemistry, transcriptome sequencing, immunofluorescence staining, qRT-PCR, Western blotting, and adeno-associated virus-mediation were employed.
The analyses indicated the presence of 97 chemical components in the aqueous extract of the decoction. The treatment improved sleep, reduced anxiety in mice, increased the levels of GABA in the hippocampus, and decreased serum ACTH, CORT, IL-6, TNF-α, and IL-1β levels. Further, the decoction displayed a protective effect on hippocampal neurons and reduced neuroinflammation. On a transcriptomic and protein level, the decoction was shown to inhibit Wnt signaling by promoting Foxj1 expression and restoring primary cilia in astrocytes. This dual effect led to the activation of the GSK-3β/GR signaling pathway, restoring HPA axis function and reversing glucocorticoid resistance, and to the suppression of β-catenin nuclear translocation and astrocyte-driven neuroinflammation.
