Metabolomics integrated with network pharmacology suggests the potential mechanisms of Chaibei Zhixian decoction in epilepsy.

OBJECTIVE

To investigate the potential mechanisms of Chaibei Zhixian Decoction in the treatment of epilepsy.

METHODS

Metabolic changes in control, epilepsy model, and treatment groups were analyzed using high-resolution liquid chromatography-mass spectrometry. Differential metabolites were identified, annotated by spectral library matching without confirmation using authentic chemical standards (Metabolomics Standards Initiative Level 2), and potential compound-target interactions were explored through network analysis, molecular docking, and molecular dynamics simulation. Gene expression of nuclear factor erythroid 2-related factor 2 and cyclooxygenase-2 was measured in a rat model of epilepsy.

RESULTS

Twenty-four differential metabolites were identified, mainly associated with lipid metabolism pathways, including glutathione metabolism and ferroptosis. Six core targets were identified, including tumor protein 53, proto-oncogene tyrosine-protein kinase, signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase catalytic subunit alpha, heat shock protein 90 alpha family class A member 1, and protein kinase B. Computational analyses suggested stable interactions between compounds and targets. Treatment was associated with increased nuclear factor erythroid 2-related factor 2 expression and decreased cyclooxygenase-2 expression.

CONCLUSIONS

Chaibei Zhixian Decoction may regulate ferroptosis-related pathways in epilepsy. These findings provide mechanistic insights; however, ferroptosis-specific markers were not measured directly, the metabolomic screen was not adjusted for multiple comparisons, and the predicted compound-target relationships require further experimental validation.