Abstract

Alzheimer's Disease (AD) is the most common form of dementia that is associated with extracellular amyloid beta (Aβ) plaque formation. Genetic, environmental, and nutrition factors have been suggested as contributors to oxidative stress and neuroinflammation events that are connected to AD etiology, and secondary metabolites, such as triterpenes, have shown promising results in AD prevention. In this work, the neuroprotective and anti-inflammatory potential of an olive leaves fraction enriched in triterpenoid compounds obtained using supercritical fluid extraction (SFE) and dynamic adsorption/desorption using sea sand as adsorbent has been performed. In addition, a comprehensive lipidomics study of the response of SH-SY5Y neuroblastoma cell line to this fraction was carried out using advanced analytical methodologies, namely, charged-surface hybrid chromatography-quadrupole-time of flight mass spectrometry (CSH-Q-TOF MS/MS). The use of freely available lipidomic annotation tools and databases, and stringent cut-off filters allowed the annotation of more than 250 intracellular lipids. Advanced bioinformatics and statistical tools showed a number of phosphatidylcholines and phosphatidylethanolamines significantly increased, which could explain the protection against the cell death caused by Aβ1–42. Moreover, several triacylglycerols were found decreased. These results suggest triterpenoids from olive leaves as good neuroprotective candidates, and open a new gate for future experiments using in vivo models to corroborate this hypothesis.

Highlights

  • Around 50 million people’ worldwide’ have dementia with nearly 10 million new cases every year [1]

  • The in vitro toxicity results obtained in this study indicate that 20 and 40 μg/mL concentrations of Olives leaves-sea sand adsorbate (OL-SS) did not alter the cell viability of differentiated SHSY5Y in comparison to control cells after 24 h, so the highest concentration (40 μg/mL) was selected to pre-treat the cells before the addition of 30 μM of the neurotoxic agent amyloid-peptide β 1–42 (Aβ1–42) [the concentration used was based on previous studies [19, 44]]

  • Ko et al [67] studied the neuroprotective effect of different lipids, PC and PS, on cultured neurons that were later exposed to Aβ1–42. They found that the pre-treatment with PC had a protective effect on neurons, whereas PS or docosahexaenoic acid ethyl-ester (DHAEE) did not prevent Aβ1–42-induced neurotoxicity [67]. All these results suggest that the OL-SS fraction could inhibit the activity of phospholipase A2 (PLA2) and/or phospholipase D1 (PLD1) enzymes, based on the increased levels of different PC species after the treatment, which might be related to the presence of triterpenoids in the olive leaves extract

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Summary

Introduction

Around 50 million people’ worldwide’ have dementia with nearly 10 million new cases every year [1]. Alzheimer’s Disease (AD) is the most common form of dementia and it may contribute to 60–70% of cases affecting about 24 million people. AD is characterized by progressive cognitive decline associated with a specific degeneration of cholinergic neurons and it usually begins with impairment in the ability to form recent memories, but inevitably affecting all intellectual functions. Current evidence indicates that Aβ plaques begin to form many years before overt dementia, and genetic, environmental, and nutrition factors have been suggested as contributors of oxidative stress [3] and neuroinflammation [4] events that are Neuroprotective Potential Olive Leaves Extract connected to AD etiology. Reactive oxygen and nitrogen species (ROS and RNS), respectively, have been shown to contribute significantly to the pathogenesis and progression of AD [5,6,7]

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