Zingerone alleviates acute seizures by reducing intrinsic hippocampal neuronal excitability in a rat model of temporal lobe epilepsy

Background: ), exhibits anti-inflammatory, antioxidant, and neuroprotective properties. However, its acute anticonvulsant efficacy and underlying mechanism in temporal lobe epilepsy (TLE) remain unclear. This study aimed to investigate whether zingerone exerts anticonvulsant effects by modulating neuronal excitability. Methods: A lithium chloride-pilocarpine-induced acute TLE rat model was established. Rats were randomly assigned to control, pilocarpine, and zingerone treatment groups (75, 150, and 300 mg/kg, i.p.). Seizure activity was evaluated via behavioral scoring (Racine scale) and electroencephalography (EEG). Immunohistochemistry (IHC), hematoxylin-eosin (HE) staining, and immunofluorescence were used to assess hippocampal microglial/astrocytic activation and neuronal damage. Whole-cell patch-clamp recordings were performed to analyze intrinsic neuronal excitability and synaptic transmission in hippocampal CA1 pyramidal neurons. Results: = 0.0001). Furthermore, Zingerone also modulated excitatory synaptic transmission onto CA1 neurons. Conclusion: Zingerone exerts acute anticonvulsant and neuroprotective effects in a TLE rat model by suppressing hippocampal neuroinflammation and reducing the intrinsic excitability of pyramidal neurons. These findings highlight zingerone as a promising natural compound for developing novel adjuvant therapies for drug-resistant TLE.