Mechanism of the effect of Xiaoyao powder treatment on exercise capacity of depressed rats—A stable isotope tracer metabolomic study

Abstract Depression accounts for 10% of the total global burden of nonfatal disease. Xiaoyao Powder, a well-known traditional Chinese medicine is commonly used to treat depression. However, its therapeutic mechanisms have not yet been fully elucidated. In this study, a rat depression model was established by the application of chronic unpredictable mild stress (CUMS). The depressed rats were randomly distributed to four groups: Blank Control, CUMS control, CUMS with Venlafaxine (a positive control) treatment, and CUMS with Xiaoyao Powder treatment, with 12 rats in each group. Depression behavioral and exercise tests were performed weekly during the four-week intervention. Stable isotope tracer metabolomics and molecular biology techniques were utilized to determine the changes in serum metabolites pre and post the intervention period, aiming to elucidate the mechanism of Xiaoyao Powder in improving the depression symptoms and exercise capacity of the depressed rats. The results found that the Xiaoyao Powder treatment significantly improved the performance in the behavioral and exercise tests, as well as affected the levels of metabolites, such as pyruvic acid, lactic acid, and citric acid in serum. It was concluded that Xiaoyao Powder intervention had a significant effect on the pyruvic acid metabolism, glycolysis/gluconeogenesis, and tricarboxylic acid cycle in the serum of the depressed rats, which could contribute to the understanding of the mechanism of the intervention. GRAPHICAL ABSTRACT