PROBABLE NITRERGIC AND CHOLINERGIC MECHANISMS INVOLVED IN THE ANTIEPILEPTIC-LIKE ACTIVITY OF SILYMARIN IN PENTYLENETETRAZOL-TREATED MICE

ABSTRACT Background: Current antiepileptic drugs (AEDs) have limitations in efficacy and side effects, underscoring the need for new therapeutic agents. Silymarin, a flavonoid complex from the milk thistle plant, has demonstrated potential due to its antioxidant, anti-inflammatory, and neuroprotective properties. This study explores the nitrergic and cholinergic mechanisms involved in the antiepileptic-like activity of silymarin in pentylenetetrazol (PTZ) kindling model of epilepsy in mice. Method: PTZ-induced kindling model of seizure was induced in adult male mice by intraperitoneal injection of PTZ (37.5 mg/kg) on alternate days for 14 days. Group 1, which served as normal control, was given saline as a vehicle (10 mL/kg, p.o.). Group 2 received PTZ (37.5 mg/kg) and vehicle (10 mL/kg, p.o.) and served as a negative control. Groups 3 and 4 received Sily (50 and 100 mg/kg, p.o.), while group 5 was administered DZP (3 mg/kg, p.o.), serving as positive control respectively, for 14 days with a 1 hr interval between treatments. Twenty-four (24) hours after the last treatment with all the drugs, mice were sacrificed and the prefrontal cortex (PFC) and hippocampus (HC) dissected to measure nitrite levels and acetylcholine esterase (AChE) activity. Results: Silymarin significantly delayed seizure onset and reduced seizure duration and severity in PTZ-treated mice. PTZ treatment significantly increased nitrite concentrations in the PFC (p < 0.0001) and HC (p < 0.01) compared to the saline group. Additionally, PTZ kindling showed no significant change in AChE activity in both brain regions compared to the saline group. Silymarin (50 mg/kg) significantly increased nitrite concentrations in the PFC (p < 0.01) without significant changes in the HC compared to the PTZ group, but has significantly (p < 0.05) reduced AChE activity in the PFC and HC compared to the PTZ group.