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阿甘油介导的 7-酮胆固醇诱导的小鼠少突胶质细胞 158N 细胞器功能障碍、氧化应激和细胞死亡的减轻作用

Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N.

机构信息

Team Bio-PeroxIL, 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' (EA7270)/University Bourgogne Franche-Comté/Inserm, 21000 Dijon, France.

Laboratory of Neuroscience and Biochemistry, Faculty of Science and Technology, University Hassan 1er, 26000 Settat, Morocco.

出版信息

Int J Mol Sci. 2017 Oct 23;18(10):2220. doi: 10.3390/ijms18102220.

DOI:10.3390/ijms18102220
PMID:29065513
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5666899/
Abstract

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25-50 µM; 24 h) without and with argan oil (0.1% /) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

摘要

阿甘油在摩洛哥传统医学中被广泛应用。它对心血管疾病的治疗作用已得到充分证实。然而,对于阿甘油在神经退行性疾病中的作用,目前还知之甚少,神经退行性疾病通常与氧化应激增加有关,导致脂质过氧化和胆固醇自动氧化生成 7-酮胆固醇(7KC)。由于 7KC 会诱导氧化应激、炎症和细胞死亡,因此确定能够削弱其有害作用的化合物非常重要。这些化合物可能是天然或合成分子,也可能是油等分子的混合物。在这种情况下:(i)通过不同的色谱技术确定了来自摩洛哥贝卡尼和阿加迪尔的膳食阿甘油的脂质谱,包括脂肪酸、植物甾醇、生育酚和多酚;(ii)评估了在含有 7KC(25-50 μM;24 小时)的 158N 小鼠少突胶质细胞中,阿甘油(0.1%/)或 α-生育酚(阳性对照,400 μM)的抗氧化和细胞保护作用,方法是使用细胞和分子生物学的补充技术。在阿甘油中存在的不饱和脂肪酸中,油酸(C18:1 n-9)和亚油酸(C18:1 n-6)最为丰富;饱和脂肪酸中含量最高的是棕榈酸(C16:0)和硬脂酸(C18:0)。还发现了几种植物甾醇,主要是菜油甾醇和角鲨烯(阿甘油特有)、环阿屯醇、β-香树脂醇和齐墩果酸。α-和γ-生育酚也存在。酪醇和原儿茶酸是唯一检测到的多酚。阿甘油和特级初榨橄榄油有许多共同的化合物,主要是油酸和亚油酸以及生育酚。自由基清除能力(KRL)和铁还原抗氧化能力(FRAP)测试表明,阿甘油和特级初榨橄榄油具有抗氧化特性。阿甘油能够减轻 7KC 对 158N 细胞的细胞毒性作用:细胞黏附丧失、细胞生长抑制、质膜通透性增加、线粒体、过氧化物酶体和溶酶体功能障碍以及氧化自噬的诱导(OXIdation + APOPTOsis + autoPHAGY)。总的来说,我们在 158N 少突胶质细胞中获得的数据表明,阿甘油能够抵抗 7KC 对神经细胞的毒性作用,这表明其某些化合物能够预防或减轻神经退行性疾病,因为它们能够穿过血脑屏障。

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