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.