Taiwe Germain Sotoing, Ndieudieu Kouamou Arielle Larissa, Dabole Bernard, Ambassa Armelle Rosalie Mbang, Mambou Hart Mann Alain Youbi, Bila Raymond Bess, Tchoya Thierry Bang, Menanga Joseph Renaud, Djomeni Dzeufiet Paul Desire, Ngo Bum Elisabeth
Department of Zoology and Animal Physiology, Faculty of Science, University of Buea, Buea, Cameroon.
Department of Animal Biology and Physiology, Faculty of Science, University of Yaounde I, Yaounde, Cameroon.
Evid Based Complement Alternat Med. 2021 Aug 30;2021:5523705. doi: 10.1155/2021/5523705. eCollection 2021.
Oxidative stress and neurodegeneration are involved in the initiation of epileptogenesis and progression of epileptic seizures. This study was aimed at investigating the anticonvulsant, antioxidant, and neuroprotective properties of active fractions isolated from root barks in pentylenetetrazole mouse models of epileptic seizures. Bioactive-guided fractionation of (AFAD) extracts using acute pentylenetetrazole (90 mg/kg) induced generalised tonic-clonic seizures, which afforded a potent anticonvulsant fraction (FPool 5). Further fractionation of AFAD was performed by high-performance liquid chromatography, which yielded fifteen subfractions, which were chemically characterised. In addition, AFAD was tested against convulsions or spontaneous kindled seizures induced, respectively, by acute (50 mg/kg) or subchronic (30 mg/kg) injection of pentylenetetrazole. Finally, oxidative stress markers, brain GABA content, and neuronal cell loss were evaluated in AFAD-treated pentylenetetrazole-kindled mice. Administration of AFAD significantly protected mice against acute pentylenetetrazole (90 mg/kg)-induced convulsions. In acute pentylenetetrazole (50 mg/kg)-induced hippocampal and cortical paroxysmal discharges, AFAD significantly decreased the number of crisis, the cumulative duration of crisis, and the mean duration of crisis. Additionally, AFAD significantly decreased the number of myoclonic jerks and improved the seizure score in subchronic pentylenetetrazole-induced kindled seizures. The pentylenetetrazole-induced alteration of oxidant-antioxidant balance, GABA concentration, and neuronal cells in the brain were attenuated by AFAD treatment. This study showed that AFAD protected mice against pentylenetetrazole-induced epileptic seizures possibly through the enhancement of antioxidant defence and GABAergic signalling. These events might be correlated with the amelioration of neuronal cell loss; hence, AFAD could be a potential candidate for the treatment of epilepsy.
氧化应激和神经退行性变参与癫痫发生的起始及癫痫发作的进展。本研究旨在探讨从根皮中分离出的活性成分在戊四氮小鼠癫痫发作模型中的抗惊厥、抗氧化和神经保护特性。采用急性戊四氮（90mg/kg）诱导全身性强直阵挛性发作，对（AFAD）提取物进行生物活性导向分级分离，得到一种有效的抗惊厥级分（FPool 5）。通过高效液相色谱对AFAD进行进一步分级分离，得到15个亚级分，并对其进行了化学表征。此外，分别通过急性（50mg/kg）或亚慢性（30mg/kg）注射戊四氮来测试AFAD对惊厥或自发点燃性癫痫发作的作用。最后，在AFAD处理的戊四氮点燃小鼠中评估氧化应激标志物、脑γ-氨基丁酸含量和神经元细胞损失情况。给予AFAD可显著保护小鼠免受急性戊四氮（90mg/kg）诱导的惊厥。在急性戊四氮（50mg/kg）诱导的海马和皮质阵发性放电中，AFAD显著减少了发作次数、发作累计持续时间和平均发作持续时间。此外，在亚慢性戊四氮诱导的点燃性癫痫发作中，AFAD显著减少了肌阵挛抽搐次数并改善了癫痫发作评分。AFAD处理减轻了戊四氮诱导的脑内氧化还原平衡、γ-氨基丁酸浓度和神经元细胞的改变。本研究表明，AFAD可能通过增强抗氧化防御和γ-氨基丁酸能信号传导来保护小鼠免受戊四氮诱导的癫痫发作。这些事件可能与神经元细胞损失的改善相关；因此，AFAD可能是治疗癫痫的潜在候选药物。
