Antidepressant-like effects of the petroleum ether fraction of Xiaoyaosan in the CUMS rat model of depression / 药学学报

ABSTRACT

This study aimed to investigate the effect of the petroleum ether fraction of Xiaoyaosan (XY-A) in a rat depression model with consideration of an underlying mechanism based on gut microbiota and metabolomics. All procedures involving animal treatment were approved according to the Committee on the Ethics of Animal Experiments of Shanxi University. A rat model was established using the chronic unpredictable mild stress (CUMS) procedure and XY-A and venlafaxine (positive control) were used as intervention drugs. Sequencing of the 16S rRNA gene combined with LC-MS metabolomics was used to investigate the effects of XY-A on gut microbiota and metabolites in CUMS-induced depression, and Pearson correlation analysis was carried out on gut microbiota and metabolites. The results showed that XY-A significantly improved the depression-like behavior of CUMS rats and restored the level of brain-derived neurotrophic factor (BDNF) in the hippocampus. Gut microbiota analysis revealed that XY-A can increase the diversity of microbial species in CUMS rats and significantly restored the relative abundance of intestinal Rothia [Prevotella], with effects on intestinal inflammation and the production of short-chain fatty acids. Cecal content metabolomics identified twenty biomarkers that were altered by depression, whereas administration of XY-A ameliorated the changes in seventeen metabolites, with the most strongly affected metabolic pathways being linoleic acid metabolism, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and arginine and proline metabolism. Correlation analysis further showed that there was a strong relationship between the gut microbiota and the cecal content metabolites. In summary, XY-A may exert antidepressant effects by regulating the composition of the gut microbiota and the metabolites and pathways of the cecum. The results provide a reference for the potential molecular mechanism of antidepressant action of XY-A.