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.