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

Abstract

BACKGROUND: Xiaochaihu Decoction (XCHD) has shown potential in treating neurological disorders, but its mechanisms in alleviating depression remain unclear. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: XCHD ameliorates depressive-like symptoms by modulating the gut microbiota-brain axis, enhancing neuroplasticity, and reducing inflammation, suggesting its potential as an antidepressant therapy.