Villareal Myra O, Sasaki Kazunori, Margout Delphine, Savry Coralie, Almaksour Ziad, Larroque Michel, Isoda Hiroko
Faculty of Life and Environmental Sciences, University of Tsukuba, Tennodai 1-1-1, Tsukuba City, 305-8587, Japan.
Alliance for Research on North Africa (ARENA), University of Tsukuba, Tennodai 1-1-1, Tsukuba City, Ibaraki, 305-8587, Japan.
Cytotechnology. 2016 Dec;68(6):2567-2578. doi: 10.1007/s10616-016-9980-3. Epub 2016 May 7.
The health benefits of Mediterranean diet has long been reported and attributed to the consumption of virgin olive oil (VOO). Here, we evaluated the neuroprotective effect of VOO against Alzheimer's disease by determining its effect on β-amyloid (Aβ)-induced cytotoxicity and oxidative stress, and explored the possibility that its hydroxycinnamic acids (Hc acids) content contribute significantly to this effect. SH-SY5Y cells treated with or without Aβ and with VOO or Hc acids (mixture of p-coumaric acid, ferulic acid, vanillic acid, and caffeic acid) were subjected to MTT assay and the results showed that both samples alleviated Aβ-induced cytotoxicity. Furthermore, both VOO and Hc acids decreased the reactive oxygen species level. Using western blot to determine the effect of these samples on Aβ-induced activation of pERK1/2, p38, and JNK MAPKs, results revealed that both VOO and Hc acids inhibited the activation of pERK1/2 and p-p38 MAPK, but not JNK. Moreover, VOO upregulated the glycolytic enzymes genes hexokinase (HK1), and phosphofructokinase (PFKM) expression which means that VOO enhanced the energy metabolism of the neurotypic cells, and therefore suggests another mechanism by which VOO could provide protection against Aβ-induced cytotoxicity. The findings in this study suggest that VOO has a neuroprotective effect, attributable to its hydroxycinnamic acids component, against Aβ-induced cytotoxicity and oxidative stress through the inhibition of the activation of MAPKs ERK and p38 and by enhancing the energy metabolism of the neurotypic cells.
长期以来,地中海饮食对健康的益处一直有报道,并归因于初榨橄榄油(VOO)的食用。在此,我们通过测定VOO对β-淀粉样蛋白(Aβ)诱导的细胞毒性和氧化应激的影响,评估了VOO对阿尔茨海默病的神经保护作用,并探讨了其羟基肉桂酸(Hc酸)含量对此作用有显著贡献的可能性。对用或不用Aβ以及用VOO或Hc酸(对香豆酸、阿魏酸、香草酸和咖啡酸的混合物)处理的SH-SY5Y细胞进行MTT试验,结果表明两种样品均减轻了Aβ诱导的细胞毒性。此外,VOO和Hc酸均降低了活性氧水平。使用蛋白质免疫印迹法测定这些样品对Aβ诱导的pERK1/2、p38和JNK丝裂原活化蛋白激酶(MAPK)激活的影响,结果显示VOO和Hc酸均抑制pERK1/2和p-p38 MAPK的激活,但不抑制JNK。此外,VOO上调了糖酵解酶基因己糖激酶(HK1)和磷酸果糖激酶(PFKM)的表达,这意味着VOO增强了神经型细胞的能量代谢,因此提示了VOO可提供针对Aβ诱导的细胞毒性的保护作用的另一种机制。本研究结果表明,VOO具有神经保护作用,归因于其羟基肉桂酸成分,通过抑制MAPKs ERK和p38的激活以及增强神经型细胞的能量代谢,抵抗Aβ诱导的细胞毒性和氧化应激。