Anti-Oxidant and Anti-Apoptotic Effects of Berberine in Pentylenetetrazole-Induced Kindling Model in Rat

BACKGROUND AND PURPOSE: Berberine (BBR) is derived from the Berberis species and has demonstrated beneficial effects in various neurodegenerative disorders in animal models. The objective of this study was to evaluate the antiepileptic, antioxidative, and anti-apoptotic effects of BBR in a pentylenetetrazole (PTZ)-induced kindling model of epilepsy in rats. METHODS: A total of 30 male Wistar rats were randomly assigned to receive BBR (100 mg/kg, oral), sodium valproate (200 mg/kg, i.p.), or saline (0.9% NaCl, i.p.) followed by PTZ (35 mg/kg, i.p.) on alternate days until the animal developed kindling or for 10 weeks. Histopathological examination of the hippocampus; DNA fragmentation study; tests for malondialdehyde, superoxide dismutase, glutathione peroxidase, and reduced glutathione; and gene expression studies (nrf2, bcl-2, bax, and caspase 3) were conducted on whole brain tissue after 10 weeks or kindling. RESULTS: The percentage of kindled animals, histopathological score, malondialdehyde level, and caspase 3 gene expression were significantly lower in the BBR group than in the PTZ group. Superoxide dismutase levels, reduced glutathione levels, and bcl-2 gene expression were significantly higher in the BBR group than in the PTZ group. CONCLUSIONS: The present study demonstrated the anti-epileptogenic effect of BBR, which may be due to antioxidant and anti-apoptotic properties of the PTZ-induced kindling model of epilepsy.