Luteolin ameliorates pentetrazole-induced seizures through the inhibition of the TLR4/NF-κB signaling pathway

IF 2 4区 医学 Q3 CLINICAL NEUROLOGY Epilepsy Research Pub Date : 2024-02-14 DOI:10.1016/j.eplepsyres.2024.107321
Yahong Cheng , Yiyuan Zhang , Puxin Huang , Qingzhou Cheng , Hong Ding
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Abstract

Epilepsy represents a prevalent neurological disorder in the population, and the existing antiepileptic drugs (AEDs) often fail to adequately control seizures. Inflammation is recognized as a pivotal factor in the pathophysiology of epilepsy. Luteolin, a natural flavonoid extract, possesses anti-inflammatory properties and exhibits promising neuroprotective activity. Nevertheless, the precise molecular mechanisms underlying the antiepileptic effects of luteolin remain elusive. In this study, we established a rat model of epilepsy using pentylenetetrazole (PTZ) to induce seizures. A series of behavioral experiments were conducted to assess behavioral abilities and cognitive function. Histological techniques, including HE staining, Nissl staining, and TUNEL staining, were employed to assess hippocampal neuronal damage. Additionally, Western blotting, RT-qPCR, and ELISA were utilized to analyze the expression levels of proteins involved in the TLR4/IκBα/NF-κB signaling pathway, transcription levels of apoptotic factors, and levels of inflammatory cytokines, respectively. Luteolin exhibited a dose-dependent reduction in seizure severity, prolonged the latency period of seizures, and shortened seizure duration. Furthermore, luteolin prevented hippocampal neuronal damage in PTZ-induced epileptic rats and partially restored behavioral function and learning and memory abilities. Lastly, PTZ kindling activated the TLR4/IκBα/NF-κB pathway, leading to elevated levels of the cytokines TNF-α, IL-6 and IL-1β, which were attenuated by luteolin. Luteolin exerted anticonvulsant and neuroprotective activities in the PTZ-induced epileptic model. Its mechanism was associated with the inhibition of the TLR4/IκBα/NF-κB pathway, alleviating the immune-inflammatory response in the post-epileptic hippocampus.

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木犀草素通过抑制 TLR4/NF-κB 信号通路改善戊四唑诱发的癫痫发作
癫痫是一种常见的神经系统疾病,现有的抗癫痫药物(AED)往往无法充分控制癫痫发作。炎症被认为是癫痫病理生理学中的一个关键因素。木犀草素是一种天然类黄酮提取物,具有抗炎特性和良好的神经保护活性。然而,叶黄素抗癫痫作用的确切分子机制仍未确定。在这项研究中,我们利用戊四唑(PTZ)诱导癫痫发作,建立了大鼠癫痫模型。我们进行了一系列行为实验来评估大鼠的行为能力和认知功能。组织学技术包括 HE 染色、Nissl 染色和 TUNEL 染色,用于评估海马神经元损伤。此外,还利用 Western 印迹、RT-qPCR 和 ELISA 分别分析了参与 TLR4/IκBα/NF-κB 信号通路的蛋白质的表达水平、凋亡因子的转录水平和炎症细胞因子的水平。叶黄素具有剂量依赖性,可降低癫痫发作的严重程度,延长癫痫发作的潜伏期,缩短癫痫发作的持续时间。此外,叶黄素还能防止 PTZ 诱发的癫痫大鼠海马神经元损伤,并部分恢复行为功能和学习记忆能力。最后,PTZ激惹激活了TLR4/IκBα/NF-κB通路,导致细胞因子TNF-α、IL-6和IL-1β水平升高,而叶黄素可减轻这种升高。在 PTZ 诱导的癫痫模型中,木犀草素具有抗惊厥和神经保护活性。其机制与抑制TLR4/IκBα/NF-κB通路、减轻癫痫后海马的免疫炎症反应有关。
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来源期刊
Epilepsy Research
Epilepsy Research 医学-临床神经学
CiteScore
0.10
自引率
4.50%
发文量
143
审稿时长
62 days
期刊介绍: Epilepsy Research provides for publication of high quality articles in both basic and clinical epilepsy research, with a special emphasis on translational research that ultimately relates to epilepsy as a human condition. The journal is intended to provide a forum for reporting the best and most rigorous epilepsy research from all disciplines ranging from biophysics and molecular biology to epidemiological and psychosocial research. As such the journal will publish original papers relevant to epilepsy from any scientific discipline and also studies of a multidisciplinary nature. Clinical and experimental research papers adopting fresh conceptual approaches to the study of epilepsy and its treatment are encouraged. The overriding criteria for publication are novelty, significant clinical or experimental relevance, and interest to a multidisciplinary audience in the broad arena of epilepsy. Review articles focused on any topic of epilepsy research will also be considered, but only if they present an exceptionally clear synthesis of current knowledge and future directions of a research area, based on a critical assessment of the available data or on hypotheses that are likely to stimulate more critical thinking and further advances in an area of epilepsy research.
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