Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Department of Chemistry, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
Molecules. 2021 Mar 13;26(6):1592. doi: 10.3390/molecules26061592.
Experimental evidence indicates that the activation of ionotropic glutamate receptors plays an important role in neurological disorders' models such as epilepsy, cerebral ischemia and trauma. The glutamate receptor agonist kainic acid (KA) induces seizures and excitotoxic cell death in the CA3 region of the hippocampus. Thymoquinone (TQ) is the most important component of the essential oil obtained from black cumin ( L.) seeds. It has many pharmacological actions including antioxidant, anti-inflammatory, and anti-apoptotic effects. TQ was used in an in vitro experimental model of primary cultures where excitotoxicity was induced. Briefly, rat organotypic hippocampal slices were exposed to 5 µM KA for 24 h. Cell death in the CA3 subregions of slices was quantified by measuring propidium iodide fluorescence. The cross-talk between TQ, ER stress and apoptotic pathways was investigated by Western blot. In untreated slices TQ (10 µM) induced a significant increase on the PSD95 levels and it decreased the excitotoxic injury induced by KA. Additionally, TQ was able to ameliorate the KA-induced increase in unfolded proteins GRP78 and GRP94 expression. Finally, TQ was able to partially rescue the reduction of the KA-induced apoptotic pathway activation. Our results suggest that TQ modulates the processes leading to post-kainate neuronal death in the CA3 hippocampal area.
实验证据表明，离子型谷氨酸受体的激活在癫痫、脑缺血和创伤等神经疾病模型中发挥着重要作用。谷氨酸受体激动剂海人酸（KA）可诱发海马 CA3 区的癫痫发作和兴奋性细胞死亡。百里醌（TQ）是从黑孜然（L.）种子中提取的精油的主要成分。它具有许多药理作用，包括抗氧化、抗炎和抗细胞凋亡作用。TQ 曾被用于诱导兴奋性毒性的原代培养体外实验模型中。简而言之，将大鼠器官型海马切片暴露于 5µM KA 中 24 小时。通过测量碘化丙啶荧光来定量切片 CA3 亚区的细胞死亡。通过 Western blot 研究 TQ、内质网应激和凋亡途径之间的串扰。在未处理的切片中，TQ（10µM）可显著增加 PSD95 水平，并减轻 KA 诱导的兴奋性损伤。此外，TQ 能够改善 KA 诱导的未折叠蛋白 GRP78 和 GRP94 表达增加。最后，TQ 能够部分挽救 KA 诱导的凋亡途径激活的减少。我们的研究结果表明，TQ 调节了 CA3 海马区海人酸诱导的神经元死亡后的过程。
