Daidzein alleviates chronic restraint stress-induced depression-like behavior by regulating neuroinflammation and synaptic plasticity via microbiota-gut-brain axis

作者：Haixia Wang, Yadan Nie, Yanting Luo, Zuoli Sun, Yi He, Jian Yang · 发表于：Phytomedicine · 年份：2025 · DOI：10.1016/j.phymed.2025.157394 · 被引用次数：6 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Phytoestrogen effects and research

BACKGROUND: Depression is one of the most serious psychological disorders worldwide. Growing evidence suggests that the gut-brain axis plays a pivotal role in its pathophysiology. Daidzein, a naturally occurring isoflavone compound, exhibits neuroprotective properties and can be metabolized by gut microbiota into highly bioactive secondary metabolites. PURPOSE: This study aims to evaluate the antidepressant effects of daidzein and to investigate its underlying mechanisms, particularly mediated by the gut microbiome. STUDY DESIGN AND METHODS: We employed the chronic restraint stress (CRS) mice models and classic behavioral tests to investigate the therapeutic effect of daidzein. Furthermore, we used 16S rRNA sequencing and metabolomics methods to explore the regulatory effects of daidzein on key functional bacteria and metabolites after CRS exposure. Intestinal barrier function was evaluated by histopathology and FITC-dextran detection. Neuroinflammatory responses, neuronal morphology, and plasticity were also evaluated using immunofluorescence staining, western blotting, and Nissl staining. Finally, we employed an antibiotic intervention experiment to validate the pivotal role of gut microbiota in the antidepressant effect of daidzein. RESULTS: Our data demonstrate that daidzein administration mitigated the depression-like behaviors in CRS mice, with gut microbiota composition playing a potentially critical mediating role. Specifically, daidzein induced significant modulation...