De La Cruz Cortés José Pedro, Pérez de Algaba Inmaculada, Martín-Aurioles Esther, Arrebola María Monsalud, Ortega-Hombrados Laura, Rodríguez-Pérez María Dolores, Fernández-Prior María África, Bermúdez-Oria Alejandra, Verdugo Cristina, González-Correa José Antonio
Departmento de Farmacología, Facultad de Medicina, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, 29010 Málaga, Spain.
Clinical Laboratory Department, Hospital Público de Montilla, 14550 Córdoba, Spain.
Brain Sci. 2021 Aug 26;11(9):1133. doi: 10.3390/brainsci11091133.
Hydroxytyrosol (HT) is the component primarily responsible for the neuroprotective effect of extra virgin olive oil (EVOO). However, it is less effective on its own than the demonstrated neuroprotective effect of EVOO, and for this reason, it can be postulated that there is an interaction between several of the polyphenols of EVOO. The objective of the study was to assess the possible interaction of four EVOO polyphenols (HT, tyrosol, dihydroxyphenylglycol, and oleocanthal) in an experimental model of hypoxia-reoxygenation in rat brain slices. The lactate dehydrogenase (LDH) efflux, lipid peroxidation, and peroxynitrite production were determined as measures of cell death, oxidative stress, and nitrosative stress, respectively. First, the polyphenols were incubated with the brain slices in the same proportions that exist in EVOO, comparing their effects with those of HT. In all cases, the cytoprotective and antioxidant effects of the combination were greater than those of HT alone. Second, we calculated the concentration-effect curves for HT in the absence or presence of each polyphenol. Tyrosol did not significantly modify any of the variables inhibited by HT. Dihydroxyphenylglycol only increased the cytoprotective effect of HT at 10 µM, while it increased its antioxidant effect at 50 and 100 µM and its inhibitory effect on peroxynitrite formation at all the concentrations tested. Oleocanthal increased the cytoprotective and antioxidant effects of HT but did not modify its inhibitory effect on nitrosative stress. The results of this study show that the EVOO polyphenols DHPG and OLC increase the cytoprotective effect of HT in an experimental model of hypoxia-reoxygenation in rat brain slices, mainly due to a possibly synergistic effect on HT's antioxidant action. These results could explain the greater neuroprotective effect of EVOO than of the polyphenols alone.
羟基酪醇（HT）是特级初榨橄榄油（EVOO）具有神经保护作用的主要成分。然而，其单独作用时的效果不如EVOO所显示的神经保护作用显著，因此，可以推测EVOO中的几种多酚之间存在相互作用。本研究的目的是在大鼠脑片缺氧复氧实验模型中评估四种EVOO多酚（HT、酪醇、二羟基苯乙二醇和油橄榄苦素）之间可能的相互作用。分别测定乳酸脱氢酶（LDH）外排、脂质过氧化和过氧亚硝酸盐生成，作为细胞死亡、氧化应激和亚硝化应激的指标。首先，将多酚与脑片按照EVOO中存在的相同比例孵育，将它们的作用与HT的作用进行比较。在所有情况下，组合的细胞保护和抗氧化作用均大于单独使用HT时的作用。其次，我们计算了在不存在或存在每种多酚的情况下HT的浓度-效应曲线。酪醇未显著改变HT所抑制的任何变量。二羟基苯乙二醇仅在10 μM时增强了HT的细胞保护作用，而在50和100 μM时增强了其抗氧化作用，并在所有测试浓度下增强了其对过氧亚硝酸盐形成的抑制作用。油橄榄苦素增强了HT的细胞保护和抗氧化作用，但未改变其对亚硝化应激的抑制作用。本研究结果表明，在大鼠脑片缺氧复氧实验模型中，EVOO多酚DHPG和OLC增强了HT的细胞保护作用，这主要归因于它们对HT抗氧化作用可能的协同效应。这些结果可以解释EVOO比单独的多酚具有更强神经保护作用的原因。
