Vongthip Wudtipong, Sillapachaiyaporn Chanin, Kim Kyu-Won, Sukprasansap Monruedee, Tencomnao Tewin
Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Antioxidants (Basel). 2021 Oct 25;10(11):1678. doi: 10.3390/antiox10111678.
Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC-MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy-autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases.
氧化应激在神经退行性变中起关键作用。因此，减轻大脑中的氧化应激是预防神经退行性疾病的重要策略。（Rang-jued）在泰国作为一种草药茶而闻名。在此，我们旨在确定叶提取物（TLE）对谷氨酸诱导的小鼠海马细胞（HT-22）氧化应激毒性和线粒体自噬介导的细胞死亡的保护作用。我们的结果通过液相色谱-质谱联用技术揭示TLE具有高水平的生物活性抗氧化剂。我们发现用TLE预处理细胞可浓度依赖性地预防谷氨酸诱导的神经元死亡。TLE降低了细胞内活性氧水平，并维持了由谷氨酸引起的线粒体膜电位。此外，TLE上调了抗氧化酶（超氧化物歧化酶1、超氧化物歧化酶2、过氧化氢酶和谷胱甘肽过氧化物酶）的基因表达。有趣的是，谷氨酸还诱导了线粒体自噬过程的激活。然而，TLE可通过抑制自噬蛋白（微管相关蛋白1轻链3-II/微管相关蛋白1轻链3-I）的激活并增加一种特定的线粒体蛋白（外膜转位酶20）来逆转这种活性。我们的结果表明，过量的谷氨酸可通过线粒体自噬介导的细胞死亡信号通路在HT-22细胞中导致神经元死亡。我们的研究结果表明，TLE通过刺激内源性抗氧化酶并通过线粒体自噬-自噬途径抑制谷氨酸诱导的氧化毒性来保护细胞免受神经元死亡。TLE可能具有作为神经退行性疾病的替代或治疗方法的潜力。
