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腰果树叶提取物可抵御谷氨酸/血红素加氧酶诱导的氧化毒性并促进神经突生长:SIRT1/Nrf2信号通路和Ten-4跨膜蛋白的作用

Anacardium Occidentale L. Leaf Extracts Protect Against Glutamate/HO-Induced Oxidative Toxicity and Induce Neurite Outgrowth: The Involvement of SIRT1/Nrf2 Signaling Pathway and Teneurin 4 Transmembrane Protein.

作者信息

Duangjan Chatrawee, Rangsinth Panthakarn, Zhang Shaoxiong, Wink Michael, Tencomnao Tewin

机构信息

Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.

Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.

出版信息

Front Pharmacol. 2021 Apr 23;12:627738. doi: 10.3389/fphar.2021.627738. eCollection 2021.

Abstract

Neurodegenerative diseases are linked to neuronal cell death and neurite outgrowth impairment that are often caused by oxidative stress. Natural products, which have neuroprotective against oxidative stress and neurite outgrowth inducing activity, could be potential candidates for alternative treatment of neurodegenerative diseases. This study aims to investigate the neuroprotective effects and neuritogenesis properties of leaf extracts in cultured neuronal (HT22 and Neuro-2a) cells. We found gallic acid, catechin and quercetin as the main compounds in extracts. The extracts have a protective effect against glutamate/HO-mediated oxidative stress-induced cell toxicity. The gene expression of cellular antioxidant enzymes (SODs, GPx and, GSTs) were up-regulated by this treatment. The treatment also triggered SIRT, Nrf2 proteins as well as the mRNA transcriptions of relevant anti-oxidation genes (NQO1, GCLM, and EAAT3). We demonstrated that the extracts promote antioxidant defense in neuronal cells via the SIRT1/Nrf2 signaling pathway. Moreover, the extracts increase neurite outgrowth and Ten-4 expression in Neuro-2a cells. However, the neuritogenesis properties did not occur, when Ten-4 expression was knocked down by corresponding siRNA. These results suggest that the leaf extracts have an interesting neuritogenesis and neuroprotective potential against glutamate/HO-mediated toxicity and could be a potential therapeutic candidate for neurodegenerative diseases.

摘要

神经退行性疾病与通常由氧化应激引起的神经元细胞死亡和神经突生长受损有关。对氧化应激具有神经保护作用且具有诱导神经突生长活性的天然产物,可能是神经退行性疾病替代治疗的潜在候选物。本研究旨在研究叶提取物在培养的神经元(HT22和Neuro-2a)细胞中的神经保护作用和神经发生特性。我们发现没食子酸、儿茶素和槲皮素是提取物中的主要化合物。提取物对谷氨酸/羟基自由基介导的氧化应激诱导的细胞毒性具有保护作用。这种处理上调了细胞抗氧化酶(超氧化物歧化酶、谷胱甘肽过氧化物酶和谷胱甘肽S-转移酶)的基因表达。该处理还触发了沉默调节蛋白、核因子E2相关因子2蛋白以及相关抗氧化基因(醌氧化还原酶1、谷氨酸-半胱氨酸连接酶催化亚基和兴奋性氨基酸转运体3)的mRNA转录。我们证明提取物通过沉默调节蛋白1/核因子E2相关因子2信号通路促进神经元细胞中的抗氧化防御。此外,提取物增加了Neuro-2a细胞中的神经突生长和Ten-4表达。然而,当通过相应的小干扰RNA敲低Ten-4表达时,神经发生特性并未出现。这些结果表明,叶提取物对谷氨酸/羟基自由基介导的毒性具有有趣的神经发生和神经保护潜力,可能是神经退行性疾病的潜在治疗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74ee/8114061/77dc97e2d09b/fphar-12-627738-g009.jpg

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