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

Keywords:

• Depression
• exercise capacity
• serum
• stable isotope tracer metabolomics

Author contributions

C. Ji, W.D. Zhao, and J. Zheng performed the experiments. C. Ji wrote the paper. C. Ji and W.D. Zhao analyzed the data. S. Zhou, Y.M. Han, J.S. Tian, and X.M. Qin conceived and assisted in the execution of the research. All authors have understood, concurred, and approved the final edition of this manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The experiments involved in this institute were done at Shanxi University. The authors of this study thank their supporters and funding support. This work was supported by the National Natural Science Foundation of China (82074147) and Project of Natural Science Research in Shanxi Province (202103021224027).