Uncovering the antidepressant active ingredients and related molecular mechanisms of Xiaoyao Pill using integrated pharmacological strategy.

PURPOSE: To investigate antidepressant active ingredients of XYP (Xiaoyao Pill), while predicting its primary pharmacodynamic material basis and underlying mechanisms of action.

METHODS

UPLC-Q-TOF-MS/MS was used to identify the active ingredients of XYP. In addition, based on the analysis of components, network pharmacology and molecular docking were used to investigate potential therapeutic targets and possible signaling pathways of XYP in the treatment of depression.

RESULTS

A total of 102 chemical components, 10 prototype components and 16 metabolites absorbed in the brain were identified in XYP. Network pharmacology analysis showed that these compounds shared 420 common targets with depression, TP53, EGFR, PTGS2, ESR1, PPARG and other 68 targets were considered as core targets, mainly enriched in PI3K-Akt and MAPK signaling pathways. GO analysis unveiled associated apoptosis and inflammatory response. Molecular docking revealed that paeoniflorin, liquiritin, and atractylenolide III were found to have the highest binding energy to TP53, ESR1 and PPARG.

CONCLUSION

These findings suggested that XYP may exert antidepressant effects through atractylenolide III, paeoniflorin, saikosaponin D, liquiritin, formononetin, affecting the PIK3/AKT signaling pathway. This lays the foundation for the research on the quality standards and clinical rational application of traditional Chinese medicine formulas.