Multi-omics reveals the mechanisms of antidepressant-like effects of the low polarity fraction of Bupleuri Radix.

Abstract Ethnopharmacological relevance Radix Bupleuri (Bupleurum chinense DC.) is a traditional Chinese medicine that has the effect of soothing the liver and relieving depression, and widely used in the field of antidepression. Aim of the study The low polarity fraction of Bupleuri Radix (PBR) has proved to be effective for the treatment of depression based on the results of our previous study. However, mechanisms of definite antidepressant-like effects remained unclear. The purpose of this study is to reveal mechanisms of antidepressant-like effects of PBR with multi-dimensional omics. Materials and methods LC-MS metabolomics combined with 16S rRNA gene sequencing were used to investigate the effects of PBR on gut microbiota and metabolites in CUMS-induced depression, and Pearson correlation analysis was carried out on gut microbiota and metabolites. Results PBR significantly improved depression-like behaviors in the CUMS model rats. Moreover, PBR significantly increased the levels of BDNF in the hippocampus. Cecum contents metabolomics revealed that 16 biomarkers associated with PBR antidepressant effect were screened, which were involved 3 metabolic pathways including primary bile acid biosynthesis, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism. Gut microbiota further analysis demonstrated that PBR increased the diversity of gut microbiota, and significantly inhibited the growth of [Prevotella] and Ochrobactrum. Furthermore, Pearson analysis revealed there was a strong correlation between cecum contents of metabolites and gut microbiota. Conclusions PBR improved depression-like behavior by regulating metabolic profiles and gut microbiota, and contributing to further understand the entailed antidepressant-like mechanisms of PBR.