Esteban-Fernández A, Rendeiro C, Spencer J P E, Del Coso D Gigorro, de Llano M D González, Bartolomé B, Moreno-Arribas M V
Instituto de Investigación en Ciencias de la Alimentación (CIAL), CSIC-UAM, Madrid, Spain; Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK.
Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign , Champaign, IL , USA.
Front Nutr. 2017 Mar 14;4:3. doi: 10.3389/fnut.2017.00003. eCollection 2017.
Moderate wine consumption has shown the potential to delay the onset of neurodegenerative diseases. This study investigates the molecular mechanisms underlying the protective effects of wine-derived phenolic and aroma compounds in a neuroinflammation model based on SIN-1 stress-induced injury in SH-SY5Y neuroblastoma cells. Cell pretreatment with microbial metabolites found in blood after wine consumption, 3,4-dihydroxyphenylacetic (3,4-DHPA), 3-hydroxyphenylacetic acids and salicylic β-d-O-glucuronide, at physiologically concentrations (0.1-10 μM) resulted in increased cell viability versus SIN-1 control group ( < 0.05). Results also showed significant decreases in mitogen-activated protein kinase (MAPK) p38 and ERK1/2 activation as well as in downstream pro-apoptotic caspase-3 activity by some of the studied compounds. Moreover, pretreatment with p38, MEK, and ERK1/2-specific inhibitors, which have a phenolic-like structure, also resulted in an increase on cell survival and a reduction on caspase-3 activity levels. Overall, these results contribute with new evidences related to the neuroprotective actions of wine, pointing out that wine-derived human metabolites and aroma compounds may be effective at protecting neuroblastoma cells from nitrosative stress injury by inhibiting neuronal MAPK p38 and ERK1/2, as well as downstream caspase 3 activity.
适度饮酒已显示出延缓神经退行性疾病发病的潜力。本研究在基于SIN-1应激诱导损伤的SH-SY5Y神经母细胞瘤细胞神经炎症模型中，研究葡萄酒衍生的酚类和香气化合物保护作用的分子机制。用饮酒后血液中发现的微生物代谢产物3,4-二羟基苯乙酸（3,4-DHPA）、3-羟基苯乙酸和水杨酸β-d-O-葡萄糖醛酸在生理浓度（0.1-10μM）下对细胞进行预处理，与SIN-1对照组相比，细胞活力增加（<0.05）。结果还显示，一些研究化合物可使丝裂原活化蛋白激酶（MAPK）p38和ERK1/2的激活以及下游促凋亡半胱天冬酶-3的活性显著降低。此外，用具有酚类结构的p38、MEK和ERK1/2特异性抑制剂进行预处理，也可提高细胞存活率并降低半胱天冬酶-3的活性水平。总体而言，这些结果为葡萄酒的神经保护作用提供了新的证据，指出葡萄酒衍生的人体代谢产物和香气化合物可能通过抑制神经元MAPK p38和ERK1/2以及下游半胱天冬酶3的活性，有效保护神经母细胞瘤细胞免受亚硝化应激损伤。
