OBJECTIVE: To evaluate the effects of Rongchang capsule and Xifeng capsule on pentylenetetrazoleinduced epilepsy in zebrafish larvae and to explore the possible mechanisms behind their actions.METHODS: We utilized a trajectory tracking system to monitor seizures in zebrafish larva to confirm that certain concentrations of Rongchang capsule and Xifeng capsule produce antiepileptic effects.c-fos expression was assessed by quantitative reverse transcription-polymerase chain reaction to validate the efficacy of the capsules. Rest/wake behavior and correlation analysis predicted the targets of Rongchang capsule and Xifeng capsule.RESULTS: Larval movement times and total distances traveled by zebrafish larvae experiencing pentylenetetrazole(PTZ)-induced seizures were decreasedbyvalproatetreatment.Rongchang(500 μg/m L) and Xifeng(200 μg/m L) rescued the epileptic behaviors and down-regulated c-fos expression in the brains of larvae, which indicated antiepileptic effects. The rest/wake behavioral profiles showed that Rongchang and Xifeng differentially decreased rest time at night and increased larval locomotor activities during the day. Based on correlation between the actions of the two capsules and known compounds, we predicted that they might change rest/wake behaviors by affecting serotonin, GABAergic and histamine signaling pathways.CONCLUSION: The efficacy of Rongchang capsule and Xifeng capsule in alleviating epilepsy-like behaviors and molecular responses was confirmed.Our study provides insight into the capsules' effect on epilepsy.