Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the Netherlands; Biomedical Sciences of Cells & Systems, Molecular Neurobiology, Faculty of Medical Sciences, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Neuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area- School of Medicine, SIU, University of Antioquia, Medellín, Colombia.
Department of Molecular Pharmacology, Faculty of Science and Engineering, Groningen Research Institute of Pharmacy, Behavioral and Cognitive Neurosciences (BCN), University of Groningen, Groningen, the Netherlands.
Biomed Pharmacother. 2019 Oct;118:109295. doi: 10.1016/j.biopha.2019.109295. Epub 2019 Sep 6.
Mitochondrial dysfunction and inflammation contribute to the initiation and development of several brain pathological conditions, including Alzheimer's disease and cerebral ischemia. Linalool is an aromatic plant-derived monoterpene alcohol with reported anti-inflammatory, and anti-oxidant properties. We investigated the role of linalool on glutamate-induced mitochondrial oxidative stress in immortalized neuronal HT-22 cells. Glutamate induced oxidative stress in neuronal cells, as detected by real-time cell impedance measurements, MTT assay, and analysis of Annexin V/PI. Administration of linalool 100 μM reduced cell death mediated by glutamate. Staining of glutamate-stimulated mitochondria by MitoTracker revealed improved morphology in the presence of linalool. Furthermore, we demonstrated a potential neuroprotective effect of linalool in conditions of oxidative stress by a reduction of mitochondrial ROS and mitochondrial calcium levels, and by preserving mitochondrial membrane potential. Experiments using both high-resolution respirometry and Seahorse Extracellular flux analyzer showed that linalool was able to promote an increase in uncoupled respiration that could contribute to its neuroprotective capacity. Linalool protection was validated using organotypic hippocampal slices as ex vivo model with NMDA as a stimulus to induce excitotoxity cell damage. These results demonstrate that linalool is protective in an in vitro model of glutamate-induced oxidative stress and in an ex-vivo model for excitotoxity, proposing linalool as a potential therapeutic agent against neurodegenerative brain diseases where oxidative stress contributes to the pathology of the disease.
线粒体功能障碍和炎症导致了几种大脑病理状况的发生和发展，包括阿尔茨海默病和脑缺血。芳樟醇是一种具有抗炎和抗氧化特性的芳香植物衍生的单萜醇。我们研究了芳樟醇对谷氨酸诱导的永生化神经元 HT-22 细胞线粒体氧化应激的作用。通过实时细胞阻抗测量、MTT 测定和 Annexin V/PI 分析检测到谷氨酸诱导神经元细胞发生氧化应激。100 μM 的芳樟醇可减少谷氨酸介导的细胞死亡。用 MitoTracker 对谷氨酸刺激的线粒体进行染色，结果显示在芳樟醇存在的情况下线粒体形态得到改善。此外，我们通过降低线粒体 ROS 和线粒体钙水平以及维持线粒体膜电位，证明了芳樟醇在氧化应激条件下具有潜在的神经保护作用。使用高分辨率呼吸测定法和 Seahorse 细胞外通量分析仪进行的实验表明，芳樟醇能够促进解偶联呼吸的增加，这可能有助于其神经保护能力。使用 NMDA 作为刺激物诱导兴奋性毒性细胞损伤的器官型海马切片作为离体模型验证了芳樟醇的保护作用。这些结果表明，芳樟醇在体外谷氨酸诱导的氧化应激模型和离体兴奋性毒性模型中具有保护作用，表明芳樟醇可能是一种对抗氧化性脑疾病的潜在治疗药物，其中氧化应激是疾病发生的原因之一。
