Gastrodia elata Blume and Acorus tatarinowii Schott mixtures alleviate pentylenetetrazol-induced seizures in mice: association with NLRP3 inflammasome signaling changes.

OBJECTIVE: To evaluate therapeutic mechanism of Gastrodia elata Blume and Acorus tatarinowii Schott (GEAT) herb pair in the treatment of epilepsy. METHODS: The anti-seizure effects were evaluated using the maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced acute and kindling seizures. Seizure behaviors and electroencephalography (EEG) activity were assessed. Cognitive function, hippocampal pathology, ultrastructure and key targets NLRP3, caspase-8 and BDNF were also examined. Additionally, network pharmacology and molecular docking analyses were integrated to complement the experimental findings. KEY FINDINGS: GEAT reduced the generalized seizures in the MES model. In the PTZ model, GEAT decreased the seizure stages, prolonged the latent period of epileptic seizures, and decreased the death rate. In the chronic PTZ model, GEAT significantly reduced the Racine score during the kindling process, suppressed spontaneous seizures and EEG abnormalities. It also effectively alleviated cognitive memory impairment and anxiety-like behavior. Furthermore, GEAT attenuated hippocampal neuronal loss, microglial and astrocytes activation and mitochondrial damage, and regulated BDNF, Caspase-8, NLRP3, Caspase-1 and IL-1β protein expression. CONCLUSION: GEAT exerts multi-target effects against epilepsy, associated with synergistic regulation of glial activation, neuroinflammation, and apoptosis involving the NLRP3/caspase-1/IL-1β pathway, thereby providing a robust theoretical and experimental foundation for its clinical translation.