Protective effects of Biarum carduchrum ethyl acetate extract on seizure severity, depression, memory, and learning in pentylenetetrazole-induced kindling rats Running title: Biarum carduchrum effects on seizure, oxidative stress, and cognitive impairment

Abstract

Background: Based on traditional beliefs, Biarum carduchrum (family Araceae) can strengthen the nervous system and prevent from sleep disorder and agitation. Objectives: This study was performed to investigate the protective effects of the ethyl acetate extract of Biarum carduchrum leaves against pentylenetetrazol (PTZ)-induced seizure in rats. Methods: The present experimental research was conducted on 50 male Wistar rats in Iran during 2019. The animals were examined in five groups of control, PTZ, intervention (PTZ with 100 and 200 mg/kg ethyl acetate extract for 10 days), diazepam (PTZ, 200 mg/kg extract, and diazepam). The research groups were compared in terms of behaviors. Furthermore, total phenol and flavonoid levels in the extract were determined using high-performance liquid chromatography. Results: According to the results, the intervention and diazepam groups had a significantly lower number of the whole body, tonic, head, and upper organ seizures (P<0.05), and jumps (P<0.05), compared to the PTZ group. Both doses of the extract also significantly decreased immobility time in tail suspension and secondary latency time and significantly enhanced spatial memory in Morris water maze test (P<0.05). This treatment also significantly reduced the levels of nitric oxide and malondialdehyde in the brain and serum (P<0.05) and showed antioxidant activity (IC50=200 μg/ml). The extract contained 42.63±0.7494 and 85.16±6.499 µg/mg phenol and flavonoid, respectively. The HPLC analysis also revealed the presence of quercetin (30 μg/g) in the extract. Conclusions: Based on the results, Biarum carduchrum extract can be used for depression control and improvement of learning and memory impairments in seizure patients after complementary testing.