Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N.

Asmaa Badreddine,Wiem Meddeb,Thomas Nury,Maryem Bezine,Amira Zarrouk,Lucy Martine,Stéphane Grégoire,Philippe Durand,Emmanuelle Prost-Camus,Meryam Debbabi,Anne Vejux,Thibault Moreau,Michel Prost,Randa Sghaier,Mustapha Cherkaoui-Malki,El Mostafa Karym,Gérard Lizard,Lionel Bretillon,Boubker Nasser

doi:10.3390/ijms18102220

Abstract

Argan oil is widely used in Morocco in traditional medicine. Its ability to treat cardiovascular diseases is well-established. However, nothing is known about its effects on neurodegenerative diseases, which are often associated with increased oxidative stress leading to lipid peroxidation and the formation of 7-ketocholesterol (7KC) resulting from cholesterol auto-oxidation. As 7KC induces oxidative stress, inflammation and cell death, it is important to identify compounds able to impair its harmful effects. These compounds may be either natural or synthetic molecules or mixtures of molecules such as oils. In this context: (i) the lipid profiles of dietary argan oils from Berkane and Agadir (Morocco) in fatty acids, phytosterols, tocopherols and polyphenols were determined by different chromatographic techniques; and (ii) their anti-oxidant and cytoprotective effects in 158N murine oligodendrocytes cultured with 7KC (25–50 µM; 24 h) without and with argan oil (0.1% v/v) or α-tocopherol (400 µM, positive control) were evaluated with complementary techniques of cellular and molecular biology. Among the unsaturated fatty acids present in argan oils, oleate (C18:1 n-9) and linoleate (C18:1 n-6) were the most abundant; the highest quantities of saturated fatty acids were palmitate (C16:0) and stearate (C18:0). Several phytosterols were found, mainly schottenol and spinasterol (specific to argan oil), cycloartenol, β-amyrin and citrostadienol. α- and γ-tocopherols were also present. Tyrosol and protocatechic acid were the only polyphenols detected. Argan and extra virgin olive oils have many compounds in common, principally oleate and linoleate, and tocopherols. Kit Radicaux Libres (KRL) and ferric reducing antioxidant power (FRAP) tests showed that argan and extra virgin olive oils have anti-oxidant properties. Argan oils were able to attenuate the cytotoxic effects of 7KC on 158N cells: loss of cell adhesion, cell growth inhibition, increased plasma membrane permeability, mitochondrial, peroxisomal and lysosomal dysfunction, and the induction of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY). Altogether, our data obtained in 158N oligodendrocytes provide evidence that argan oil is able to counteract the toxic effects of 7KC on nerve cells, thus suggesting that some of its compounds could prevent or mitigate neurodegenerative diseases to the extent that they are able to cross the blood-brain barrier.

Highlights

Lipids are a group of various organic substances
We focused on the fatty acids, phytosterols, polyphenols and tocopherols present in argan oil
These oxides are derived from the auto-oxidation of cholesterol and are known for their cytotoxic activities [48,49,50]. α- and γ-tocopherols were the most abundant tocopherols: the highest level of αtocopherol was detected in argan oil from Agadir, the lowest level in argan oil from Berkane; the highest level of γ-tocopherol was detected in argan oil from Berkane, the lowest level in argan oil from Agadir; δ-tocopherol was always present at low concentrations (Table 3)

Summary

Introduction

Lipids are a group of various organic substances. They are non-polar molecules that are soluble in organic solvents but not in water and are formed of carbon, hydrogen, oxygen and sometimes phosphorus, nitrogen and sulfur. The fats in breast milk and its substitutes are essential for brain development, and lipids are the source of infant dietary energy These lipids are mainly fatty acids (FA): monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids, cholesterol and complex lipids [1,2,3,4]. Based on numerous studies, dietary lipids appear to be essential for the healthy development and functioning of the brain, and some of them could prevent neurodegeneration and delay brain aging [17,18,19] In this context, it is important to take into account the fatty acid and nutrient profiles of edible oils, and to know more about their biological activities. It is possible that the consumption of certain oils recognized for their beneficial effects on health such as argan oil, used in Morocco, and olive oil, widely associated with the Mediterranean diet, could have beneficial effects on the brain [20]

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Discussion

Conclusion