A Potent Lignan from Prunes Alleviates Inflammation and Oxidative Stress in Lithium/Pilocarpine-Induced Epileptic Seizures in Rats

Prunus domestica L. is an edible plant that is included in the family Rosaceae and proven to possess potent anti-inflammatory and anxiolytic activity. Pinoresinol-4-O-β-d-glucopyranoside (PGu) was isolated from Prunus domestica methanol extract and its structure was determined using 1-D and 2-D NMR (one- and two-dimensional nuclear magnetic resonance). PGu was evaluated for its anticonvulsant activity using lithium/pilocarpine-induced epileptic seizures in rats. PGu displayed a notable antioxidant and anti-inflammatory activity in vitro. It ameliorates the seizures triggered by pilocarpine in a dose-dependent manner, manifested by retarding seizure onset, reducing the number of rats developing seizures, and enhancing the survival of animals after seizure exposure. PGu reduced MDA (malondialdehyde) level by 24.2% in addition to increasing catalase activity by 44.4% at 50 mg/kg b.w compared to pilocarpine-treated animals. This was confirmed by histopathological examination in which pretreatment with PGu (50 mg/kg b.w.) attenuated neurodegeneration and seizures with no histopathological alteration in neurons of the cerebral cortex. In the immunohistochemical examination, it significantly declined the elevated Cyclooxygenase-2 (COX-2) by 40% and decreased Inducible nitric oxide synthase (iNOS) expression by 18% as expressed by the optical density. PGu revealed a pronounced fitting within the active site of 5-LOX (lipoxygenase-5) with a free binding energy (∆G) equals to -65.05 kcal/mol. PGu could perfectly serve as a potent lead drug for the relief of epileptic seizures, which appeals to many patients owing to its natural origin.

Keywords: Prunus domestica; anti-inflammatory; epilepsy; oxidative stress; pilocarpine; pinoresinol-4-O-β-d-glucopyranoside.