Oxidative stress causes neuronal cell death in various neurodegenerative diseases, such as Alzheimer’s disease, ischemia, and Parkinson’s disease. Therefore, reducing intracellular reactive oxygen species (ROS) has been evaluated as an effective treatment strategy for neurodegenerative disorders. Methyl lucidone (MLC) extracted from Lindera erythrocarpa Makino (Lauraceae) has been previously reported to exhibit microglial-mediated neuroprotective effects via inhibiting neuroinflammation. However, the antioxidant effects of MLC are still unclear. The aim of this study was to determine the neuroprotective mechanism of MLC in HT-22 neurons against oxidative stress induced by glutamate. In results, the pretreatment of MLC significantly enhanced the viability of HT-22 cells under glutamate-induced oxidative conditions, suggesting that MLC has a neuronal mechanism to protect neurons without microglial regulation. Also, the glutamate effect to increase ROS production was effectively blocked by MLC without any free radical scavenging activity. To induce this antioxidant effect, MLC upregulated the expression of heme oxygenase 1 (HO-1) and nuclear translocation of nuclear factor-E2-related factor 2 (Nrf-2), known as an intracellular antioxidant enzyme, and its transcription factor. Additionally, Akt phosphorylation regulating Nrf-2 was confirmed to be involved in the neuroprotective signaling activated by MLC. These results indicate that MLC may play a role as an antioxidant agent to inhibit neurodegenerative processes via activating antioxidant signaling pathways that include Nrf-2 and phosphatidylinositol 3-kinase (PI3K).

中文翻译：

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甲基lucidone通过Nrf-2 / HO-1信号转导对谷氨酸诱导的HT-22细胞氧化应激的神经保护作用

氧化应激会导致各种神经退行性疾病（例如阿尔茨海默氏病，局部缺血和帕金森氏病）的神经元细胞死亡。因此，减少细胞内活性氧（ROS）已被评估为神经退行性疾病的有效治疗策略。先前已经报道了从Linder erythrocarpa Makino（Lauraceae）提取的甲基透明酮（MLC）通过抑制神经炎症表现出小胶质细胞介导的神经保护作用。然而，MLC的抗氧化作用仍不清楚。这项研究的目的是确定ML-22在HT-22神经元中对抗谷氨酸诱导的氧化应激的神经保护机制。结果，在谷氨酸诱导的氧化条件下，MLC的预处理显着增强了HT-22细胞的活力，提示MLC具有神经元机制来保护神经元而无小胶质细胞调节。而且，MLC有效地阻止了增加ROS产生的谷氨酸作用，而没有任何自由基清除活性。为了诱导这种抗氧化作用，MLC上调了血红素加氧酶1（HO-1）的表达和称为细胞内抗氧化酶的核因子E2相关因子2（Nrf-2）的核转运及其转录因子。此外，证实调节Akt磷酸化Nrf-2参与了MLC激活的神经保护信号传导。这些结果表明，MLC可能通过激活包括Nrf-2和磷脂酰肌醇3-激酶（PI3K）的抗氧化剂信号传导途径，作为抗氧化剂来抑制神经退行性过程。