Depression is one of the most prevalent and serious mental disorders with a significant burden of disease. Xiaoyaosan（XYS）, a well-known Chinese formula, has been widely used in the treatment of depression. Both clinical studies and animal experiments have indicated that XYS has an obvious antidepressant activity. How to select objective pharmacodynamic markers for traditional Chinese medicine（TCM） treatments based on clinical metabolites, linking pathogenic genes, and drug targets, is a bottleneck problem in the modernization of TCM. To address this issue, we sorted out clinical metabonomics experiments of XYS in treating depression, constructed a metabolic profile of therapeutic biomarkers, and deduced metabolic biomarker-protein interactions networks. The therapeutic biomarkers found for XYS were involved in neurotransmitter synthesis, energy metabolism, and gut microbial metabolism. This study aims to provide a scientific basis for the clinical diagnosis of depression and evaluate the efficacy of XYS in its treatment.
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