Abstract
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.