Anti-depression mechanisms of Xiaoyao Powder based on fecal metabolomics / 中草药

ABSTRACT

Objective: To characterize the endogenous metabolites and metabolic changes of feces of chronic unpredictable mild stress (CUMS) rats by 1H-NMR, evaluate the improvement effects of Xiaoyao Powder and investigate the underlying mechanisms. Methods: The depression model was established by CUMS procedure. 1H-NMR coupled with multivariate statistical analysis was employed to reveal the changes of fecal metabolic profiles of CUMS rats and identify potential bio-markers involved in CUMS-induced depression. Based on the potential bio-markers, the relevant metabolic pathways were constructed. Results: A total of 10 metabolites was identified as potential bio-markers in fecal samples for the CUMS model. Compared with the control group, the contents of asparagine, aspartate, lactate and propionic acid in the CUMS rats were significantly increased (P < 0.05, 0.01), while phenylalanine, tyrosine, glutamate, glutamine, alanine and proline were significantly decreased (P < 0.05, 0.01). The administration of Xiaoyao Powder could significantly increase the levels of phenylalanine, tyrosine, glutamate, glutamine and proline, whereas reduced the levels of asparagine, lactate and propionic acid. Compared with the control group, six metabolic pathways were recognized as the most influenced pathways associated with the CUMS-induced depression (1) aminoacyl-tRNA biosynthesis, (2) alanine, aspartate and glutamate metabolism, (3) arginine and proline metabolism, (4) glutamine and glutamate metabolism, (5) phenylalanine metabolism and (6) pyruvate metabolism. Among them, Xiaoyao Powder significantly mediated abnormalities of five pathways of (2), (3), (4), (5) and (6). Conclusion: It is the first report to investigate the antidepressant-like effects and underlying mechanisms of Xiaoyao Powder from the perspective of fecal metabolites. The current results showed that the anti-depression mechanisms of Xiaoyao Powder might be related to regulating the amino acid metabolism, glucose metabolism and intestinal microbial metabolism. This study provides a solid basis for revealing the anti-depression mechanisms of Xiaoyao Powder comprehensively and deeply.