Sakuranetin exerts anticonvulsant effect in bicuculline-induced seizures

Epilepsy is a chronic neurological disorder characterized by an abnormal, spontaneous, and synchronized neuronal hyperactivity. Therapeutic approaches for controlling epileptic seizures are associated with pharmacoresistance and side effects burden. Previous studies reported that different natural products may have neuroprotector effects. Sakuranetin (SAK) is a flavanone with antiparasitic, anti-inflammatory, antimutagenic, antiallergic, and antioxidant activity. In the present work, the effect of SAK on seizures in a model of status epilepticus induced by bicuculline (BIC) in mice was evaluated. Male Swiss mice received an intracerebroventricular injection (i.c.v.) of SAK (1, 10, or 20 mg/kg-SAK1, SAK10, or SAK20). Firstly, animals were evaluated in the open field (OF; 20 min), afterwards in the elevated plus maze (EPM) test (5 min). Next, 30 min prior the administration of BIC (1 mg/kg), mice received an injection of SAK (1 or 10 mg/kg, i.c.v.) and were observed in the OF (20 min) for seizures assessment. After behavioral procedures, immunohistochemical analysis of c-Fos was performed. Our main results showed that the lowest doses of SAK (1 and 10 mg/kg) increased the total distance traveled in the OF, moreover protected against seizures and death on the BIC-induced seizures model. Furthermore, SAK treatment reduced neuronal activity on the dentate gyrus of the BIC-treated animals. Taken together, our results suggest an anticonvulsant effect of SAK, which could be used for the development of anticonvulsants based on natural products from herbal source.