Berberine exerts an anticonvulsant effect and ameliorates memory impairment and oxidative stress in a pilocarpine-induced epilepsy model in the rat

Abstract

Fei Gao,1,* Ying Gao,2,* Yang-feng Liu,3 Li Wang,4 Ya-jun Li1 1Department of Neurology, First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 2Department of Radiotherapy Oncology, First Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Department of Neurology, People’s Liberation Army No. 451 Hospital, Xi’an, People’s Republic of China; 4Department of Scientific Research, First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China *These authors contributed equally to this work Abstract: Though new antiepileptic drugs are emerging, approximately a third of epileptic patients still suffer from recurrent convulsions and cognitive dysfunction. Therefore, we tested whether berberine (Ber), a vegetable drug, has an anticonvulsant property and attenuates memory impairment in a pilocarpine (Pilo)-induced epilepsy model in rats. The rats were injected with 400 mg/kg Pilo to induce convulsions, and Ber 25, 50, and 100 mg/kg were administrated by the intragastric route once daily 7 days before Pilo injection until the experiment was over. Convulsions were observed after Pilo injection. For the rats that developed status epilepticus (SE), malondialdehyde, glutathione levels, superoxide dismutase, and catalase activity in the hippocampus were measured 24 hours after SE. The rats received the Morris water-maze test 2 weeks after SE, and then were killed for fluoro-jade B staining to detect the degenerating neurons. We found Ber delayed latency to the first seizure and the time to develop SE in a dose-dependent manner. Malondialdehyde levels were decreased, while glutathione and catalase activity were strengthened in Ber-injected SE rats. In the Morris water-maze test, Ber decreased escape latency compared to saline-treated SE rats. Additionally, Ber reduced the number of fluoro-jade B-positive cells in the hippocampal CA1 region. Our data suggest that Ber exerts anticonvulsant and neuroprotective effects on Pilo-induced epilepsy in rats. Simultaneously, Ber attenuates memory impairment. The beneficial effect may be partly due to mitigation of the oxidative stress burden. Keywords: status epilepticus, pilocarpine, memory impairment, oxidative stress, neuroprotection