OBJECTIVE

To reveal the safety, efficacy, and mechanism of action of et Folium (TCEF) for treating depression.

METHODS

The maximum dose method was employed to evaluate the safety of TCEF, and its antidepressant activity was assessed using the tail suspension and sugar water depletion tests. The main components of TCEF were determined using ultrahigh performance liquid chromatography coupled with quadrupole exactive orbitrap mass spectrometer (UHPLC-Q-EOMS). The active ingredients and their action targets were obtained using network pharmacology with SwissADME and SwissTargetPrediction screening, and the targets of depression were obtained using GeneCards, DrugBank, etc. The drug and depression-related targets were intersected and analyzed PPI network, GO, and KEGG. Subsequently, the binding ability of the core components of TCEF to the core targets was validated molecular docking and simulation.

RESULTS

No statistically significant difference was observed between the normal and TCEF groups in terms of body weight, visceral index, and biochemical parameters ( > 0.05). Compared with the model group, all dose groups of TCEF had reduced the immobility time of tail suspension ( < 0.05) and increased the rate of sugar water consumption ( < 0.05). UHPLC-Q-EOMS was employed to identify 59 major components of TCEF, and network pharmacology analysis was used to screen 48 active components of TCEF for treating depression, corresponding to 139 relevant targets, including ALB, AKT1, TNF, ESR1, and CTNNB1. The involved pathways include neuroactive ligand-receptor interaction. The molecular docking results indicated that the core components have a good binding activity to the core targets.

CONCLUSIONS

TCEF is a relatively safe antidepressant medicine that exerts therapeutic effects through multiple components, targets, and pathways, providing a new idea and theoretical basis for future use of TCEF to treat depression.