A Potent Lignan from Prunes Alleviates Inflammation and Oxidative Stress in Lithium/Pilocarpine-Induced Epileptic Seizures in Rats
Youssef, Fadia S; Menze, Esther; Ashour, Mohamed L.;
Abstract
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.
Other data
Title | A Potent Lignan from Prunes Alleviates Inflammation and Oxidative Stress in Lithium/Pilocarpine-Induced Epileptic Seizures in Rats | Authors | Youssef, Fadia S; Menze, Esther ; Ashour, Mohamed L. | Keywords | Prunus domestica; anti-inflammatory; epilepsy; oxidative stress; pilocarpine; pinoresinol-4-O-β-d-glucopyranoside | Issue Date | 2-Jul-2020 | Publisher | MDPI | Journal | Antioxidants (Basel, Switzerland) | ISSN | 2076-3921 | DOI | 10.3390/antiox9070575 | PubMed ID | 32630680 | Scopus ID | 2-s2.0-85087415562 | Web of science ID | WOS:000554164100001 |
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