Anticonvulsant activity of β-caryophyllene in association with pregabalin in a seizure model in rats

Epilepsy is a common chronic neurological disease. The hallmark of epilepsy is recurrent, unprovoked seizures. Unfortunately, drug resistance is frequent in patients with epilepsy, and therefore improved therapeutic strategies are needed. In the present study, we tested the effect of pregabalin in association with beta-caryophyllene, an FDA-approved food additive and naturally occurring agonist of cannabinoid receptor subtype 2 against pentylenetetrazol (PTZ)-induced seizures in rats. In addition, selected neurochemical parameters were evaluated in the cerebral cortex. Adult male Wistar rats received beta-caryophyllene (100 mg/kg), pregabalin (40 mg/kg) or their combination before PTZ (60 mg/kg). Appropriated vehicle-treated control groups were included for each treatment. Animals were monitored by video-EEG and the latency to myoclonic seizures, latency to tonic-clonic seizures, tonic-clonic seizure duration and overall seizure score were measured. Glial fibrillary acidic protein (GFAP) release, erythroid-related factor 2 (Nrf2), c-fos and 3-nitrotyrosine (3-NT) levels were evaluated in the frontal cortex. We found that beta-caryophyllene plus pregabalin increased the latency to PTZ-induced myoclonic and tonic-clonic seizures and decreased the tonic-clonic seizure duration and overall seizure score. Interestingly, lower levels of GFAP, c-Fos and 3-NT were observed in animals receiving beta-caryophyllene and pregabalin treatments. Our results suggest a possible synergic effect of beta-caryophyllene plus pregabalin against PTZ induced-seizures.

Automated summary

This study tested the effects of beta-caryophyllene and pregabalin combination on PTZ-induced seizures in rats. The results showed that the combination treatment increased seizure latency, decreased seizure duration and overall seizure score, and reduced neurochemical parameters.