Xiaochaihu decoction alleviates chronic stress-induced depressive-like behavior in mice by modulating the gut...

Xiaochaihu Decoction (XCHD) has shown potential in treating neurological disorders, but its mechanisms in alleviating depression remain unclear.

The aim of this study was to examine if the XCHD was able to alleviate depressive-like impairment in a mouse model of chronic mild stress.

Fifty male C57BL/6 mice were divided into five groups: control (CON), stress (CUMS), stress with low and high XCHD doses (CUMS+L-XCHD, CUMS+H-XCHD), and fluoxetine (CUMS+FLX). The deprssion model was established using chronic unpredictable mild stress (CUMS) and isolated feeding. Animal behavior was assessed using the sucrose preference and open-field tests. Neuroplasticity, inflammation, and gut microbiota were analyzed using Western blotting, immunofluorescence, and 16S rRNA sequencing.

XCHD increased sucrose consumption and improved spatial learning and memory in stressed mice. It also alleviated anxiety and behavioral despair, restored hippocampal neuroplasticity, and reduced inflammation. XCHD modulated the Nogo-A/S1P2R-Gαq-PKC signaling pathway and enhanced tight junction proteins in the colon. Additionally, XCHD restored gut microbiota balance, increasing Firmicutes and reducing Bacteroides and Proteobacteria.

XCHD ameliorates depressive-like symptoms by modulating the gut microbiota-brain axis, enhancing neuroplasticity, and reducing inflammation, suggesting its potential as an antidepressant therapy.