Ferulic Acid Attenuates Seizure Severity and Enhances Valproate and Carbamazepine Seizure Preventing Efficacy by Regulating Hippocampal Interleukin‐1β Level and Antioxidant Capacity in Mice

Epilepsy is a neurological brain disease characterized by multiple seizures with short intervals and becomes drug‐resistant when it causes oxidative stress and inflammation in the brain. Ferulic acid (FA) is a plant phenolic substance with antioxidant, anti‐inflammatory, and neuroprotective effects that is used in the treatment of neurodegenerative diseases in traditional medicine. This study evaluated the effect of FA (20 or 80 mg/kg) alone and then FA (20 mg/kg) combined with valproate (VPA) or carbamazepine (CBZ) on maximal electroshock‐induced seizures (MESs) in mice associated with interleukin‐1β (IL‐1β) concentrations and total antioxidant capacity (TAC) assessment in the hippocampus. Male NMRI mice (weight 25–30 g) were injected intraperitoneally with saline (1 mL/kg), FA (20 or 80 mg/kg), diazepam (D) (20 mg/kg), VPA (200 mg/kg), CBZ (10 mg/kg), FA (20 mg/kg) + VPA (200 mg/kg), and FA (20 mg/kg) + CBZ (10 mg/kg) before application of MES. Duration of tonic hind limb extension (HLE), and chimney climbing time and grip‐strength were also recorded. Then, mice scarified and hippocampus removed and homogenized. The level of IL‐1β and TAC were determined. FA (20 and 80 mg/kg) significantly reduced the HLE duration and prevented seizure‐induced hippocampal IL‐1β increase and antioxidant capacity decrease. In addition, FA (20 mg/kg) enhanced the anticonvulsant efficacy of VPA and CBZ by regulating hippocampal IL‐1β and antioxidant capacity. The finding suggest that FA possessed anticonvulsant effect and improved VPA and CBZ efficacy by regulating of IL‐1β and antioxidant capacity in the hippocampus.