Puerarin ameliorates depression-like behaviors of with chronic unpredictable mild stress mice by remodeling their gut microbiota

Puerarin is an isoflavone derivative isolated from the traditional Chinese medicine Pueraria Lobelia, which has proven to relieve depression-like behavior. However, its underlying antidepressant mechanisms have been poorly characterized. Herein, we explored whether Puerarin's antidepressant effect is associated with changes in the gut microbiota (GM). The model of depression in mice featuring chronic unpredictable mild stress (CUMS) was eastablished, and its antidepressant effect was estimated by sugar water preference and forced swimming test. Genomic DNA extracted from fecal samples was employed to sequence the 16S rRNA gene for gut microbiota identification. Puerarin (100 mg/kg) treatment was found to alleviate the CUMS-induced depression-like behaviors. Furthermore, chronic stress led to pathological microbial flora, which was principally marked by the increased abundance of pathogenic bacteria (Proteobacteria, Flexispira, Desulfovibrio) and the decreased abundance of beneficial bacteria (Firmicutes, Bacillales, Lactobacillus). Intriguingly, puerarin treatment reversed these changes. The specific role and anti-depression mechanism of characteristic gut microflora were not confirmed. Puerarin can remedy stress-induced disruptions of normal gut microflora. It is suggested that the antidepressant mechanism of puerarin may closely interact with restoring beneficial microflora.