Amaghnouje Amal, Chebaibi Mohamed, Aldossari Saeed M, Ghneim Hazem K, Amrati Fatima Ez-Zahra, Es-Safi Imane, Di Cristo Francesca, Calarco Anna, Achour Sanae, Carta Fabrizio, Al-Sheikh Yazeed A, Aboul-Soud Mourad A M, Bousta Dalila
Laboratory of Biotechnology, Health, Agrofood and Environment (LBEAS), Faculty of Sciences Dhar El Mehraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco.
Ministry of Health and Social Protection, Higher Institute of Nursing Professions and Health Techniques, Fez, Morocco.
Front Chem. 2024 Jan 19;11:1257769. doi: 10.3389/fchem.2023.1257769. eCollection 2023.
Epilepsy is a chronic brain disease characterized by repeated seizures and caused by excessive glutamate receptor activation. Many plants are traditionally used in the treatment of this disease. This study aimed to evaluate the bioavailability of a polyphenolic extract obtained from L. (OMP) leaves, as well as its antiepileptic activity and its potential mechanism of action. We have developed and validated a simple, rapid, and accurate stability-indicating reversed-phase liquid chromatographic method for the simultaneous determination of caffeine and quercetin in rat plasma. The OMP antiepileptic effect was evaluated with pilocarpine-induced seizures, and a docking method was used to determine the possible interaction between caffeic acid and quercetin with the N-methyl-D-aspartate (NMDA) receptor. Both compounds tested showed low bioavailability in unchanged form. However, the tested extract showed an anticonvulsant effect due to the considerably delayed onset of seizures in the pilocarpine model at a dose of 100 mg/kg. The molecular docking proved a high-affinity interaction between the caffeic acid and quercetin with the NMDA receptor. Taken together, OLP polyphenols demonstrated good antiepileptic activity, probably due to the interaction of quercetin, caffeic acid, or their metabolites with the NMDA receptor.
癫痫是一种慢性脑部疾病，其特征为反复发作的癫痫发作，由谷氨酸受体过度激活所致。许多植物传统上被用于治疗这种疾病。本研究旨在评估从L.（OMP）叶中获得的多酚提取物的生物利用度，以及其抗癫痫活性及其潜在作用机制。我们开发并验证了一种简单、快速且准确的稳定性指示反相液相色谱法，用于同时测定大鼠血浆中的咖啡因和槲皮素。用毛果芸香碱诱导的癫痫发作评估OMP的抗癫痫作用，并采用对接方法确定咖啡酸和槲皮素与N-甲基-D-天冬氨酸（NMDA）受体之间可能的相互作用。所测试的两种化合物以未改变的形式均显示出低生物利用度。然而，在100mg/kg剂量下，所测试的提取物在毛果芸香碱模型中由于癫痫发作的起始明显延迟而显示出抗惊厥作用。分子对接证明咖啡酸和槲皮素与NMDA受体之间存在高亲和力相互作用。综上所述，OLP多酚表现出良好的抗癫痫活性，可能是由于槲皮素、咖啡酸或其代谢产物与NMDA受体的相互作用。
