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1. Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease

Author

Karym El-Mostafa, Youssef El Kharrassi, Asmaa Badreddine, Pierre Andreoletti, Joseph Vamecq, M'Hammed Saïd El Kebbaj, Norbert Latruffe, Gérard Lizard, Boubker Nasser, and Mustapha Cherkaoui-Malki

Subjects
anti-inflammatory, antioxidants, cell signaling, Opuntia ficus-indica, polyphenols, Organic chemistry, QD241-441
Abstract

Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe. In the last decade, compelling evidence for the nutritional and health benefit potential of this cactus has been provided by academic scientists and private companies. Notably, its rich composition in polyphenols, vitamins, polyunsaturated fatty acids and amino acids has been highlighted through the use of a large panel of extraction methods. The identified natural cactus compounds and derivatives were shown to be endowed with biologically relevant activities including anti-inflammatory, antioxidant, hypoglycemic, antimicrobial and neuroprotective properties. The present review is aimed at stressing the major classes of cactus components and their medical interest through emphasis on some of their biological effects, particularly those having the most promising expected health benefit and therapeutic impacts.

Published
2014
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2. Argan Oil-Mediated Attenuation of Organelle Dysfunction, Oxidative Stress and Cell Death Induced by 7-Ketocholesterol in Murine Oligodendrocytes 158N

Author

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

Subjects
argan oil, extra virgin olive oil, α-tocopherol, 7-ketocholesterol, mitochondria, lysosome, peroxisome, oxiapoptophagy, 158N murine oligodendrocytes, Biology (General), QH301-705.5, Chemistry, QD1-999
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.

Published
2017
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3. Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities

Author

John J. Mackrill, Stéphane Grégoire, Amira Zarrouk, Gérard Lizard, Mohamed Hammami, Lucy Martine, Mondher Mejri, Asmaa Badreddine, Aline Yammine, Boubker Nasser, Thomas Nury, Emmanuelle Camus, Wiem Meddeb, Mustapha Cherkaoui-Malki, Philippe Durand, Amira Namsi, Lionel Bretillon, Université de Monastir (Université de Monastir), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique (Bio-PeroxIL), Université de Bourgogne (UB), Institut Supérieur de Biotechnologie, Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Université Hassan 1er [Settat], University College Cork (UCC), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), BASIM (Association Bourguignonne pour les Applications des Sciences de l'Information en Medecine), and COST (European Cooperation in Science and Technology) CA16112

Subjects
0301 basic medicine, Antioxidant, medicine.medical_treatment, Linoleic acid, mediterranean oils, Tocopherols, Antioxidants, Cell Line, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Drug Discovery, medicine, Animals, Humans, Milk Thistle, Plant Oils, Food science, cytoprotective activities, Olive Oil, Nigella, 2. Zero hunger, Pharmacology, biology, Phytosterol, Fatty Acids, Phytosterols, Polyphenols, food and beverages, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, biology.organism_classification, antioxidant properties, Oleic acid, 030104 developmental biology, Spinasterol, chemistry, Polyphenol, 030220 oncology & carcinogenesis, Seeds, Hydroxytyrosol, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC). Results: The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels. Conclusion: Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.

Published
2019

4. Antioxidant and neuroprotective properties of Mediterranean oils: Argan oil, olive oil, and milk thistle seed oil

Author

Anne Vejux, Mondher Mejri, Fatima Zohra Bessam, Gérard Lizard, Meryam Debbabi, Boubker Nasser, Thomas Nury, Asmaa Badreddine, Leila Rezig, Amira Zarrouk, Fatiha Brahmi, and Wiem Meddeb

Subjects
food.ingredient, Antioxidant, DPPH, medicine.medical_treatment, Linoleic acid, food and beverages, Argan oil, medicine.disease_cause, Neuroprotection, Oleic acid, chemistry.chemical_compound, food, chemistry, Polyphenol, medicine, lipids (amino acids, peptides, and proteins), Food science, Oxidative stress
Abstract

Argan, olive, and milk thistle seed oils are characterized by high levels of tocopherols, mainly α-tocopherol. They are also rich in oleic acid (C18:1 n-9) and linoleic acid (C18:2 n-6) and contain small quantities of several polyphenols. As tocopherols and polyphenols have antioxidant properties and are able to cross the blood-brain barrier, it is suggested that argan, olive, and milk thistle seed oils could be useful in the prevention of neurodegenerative disorders since these are characterized by an enhancement of oxidative stress leading to neurodegeneration. This hypothesis is supported by the antioxidant properties of these oils determined by different assays KRL (Kit Radicaux Libres), FRAP (ferric-reducing antioxidant power), and DPPH [2,2-diphenyl-1-picryl-hydrazyl)] and by cytoprotective properties of these oils which are able to prevent major side effects associated with oxysterols-induced neurodegeneration such as oxidative stress, mitochondrial dysfunction, and cell death of nerve cells.

Published
2020

5. Lipid Biomarkers in Alzheimer's Disease

Author

Gérard Lizard, Mohamed Hammami, Amira Zarrouk, Mohamed El Ayeb, Thibault Moreau, Mustapha Cherkaoui-Malki, Meryam Debbabi, El Mostafa Karym, Boubker Nasser, Asmaa Badreddine, Maryem Bezine, Olivier Rouaud, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Monastir - University of Monastir (UM), Université de Sousse, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Mémoire Ressources et Recherche [Dijon] (CMRR Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Université Hassan 1er [Settat], The work on lipid biomarkers carried out by the team ‘Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism’ EA7270 / Univ. Bourgogne Franche-Comté / INSERM is financially supported by: INSERM, Université de Bourgogne, ASSAD (Louhans, France), Department of Neurology (University Hospital, Dijon, France), Memory Center, Resources and Research of Burgundy (CMRR / University Hospital, Dijon, France), and Association pour le Développement des Sciences Neurologiques en Bourgogne (ADSNB, Dijon, France) and Association Bourguignonne pour les Applications des Sciences de l'Information en Médecine (ABASIM, Dijon, France). This work was also supported by grants from: Univ. Monastir (Monastir, Tunisia), Univ. El Manar (Tunis, Tunisia), Pasteur Institut (Tunis, Tunisia), Action Intégrée of the Comité Mixte Inter-Universitaire Franco-Marocain (CMIFM, AIMA/14/310, EGIDE) from the PHC Volubilis/Toubkal program, Ministère des Affaires Etrangères, Conseil Régional de Bourgogne, Ministère de l’enseignement et de la Recherche and Projet Sectoriel CNRST.

Subjects
0301 basic medicine, medicine.medical_specialty, Lipid Metabolism Disorder, Amyloid, phospholipids, [SDV]Life Sciences [q-bio], Biology, fatty acids, lipids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Alzheimer Disease, Internal medicine, medicine, Animals, Humans, Dementia, MESH: Animals, MESH: Lipid Metabolism, MESH: Humans, Cholesterol, biomarkers, cholesterol, Lipid metabolism, Peroxisome, Lipid Metabolism, medicine.disease, MESH: Lipids, 3. Good health, 030104 developmental biology, Endocrinology, Neurology, chemistry, Docosahexaenoic acid, Alzheimer, MESH: Biomarkers, oxysterols, lipids (amino acids, peptides, and proteins), Neurology (clinical), Alzheimer's disease, MESH: Alzheimer Disease, 030217 neurology & neurosurgery
Abstract

Background: There are now significant evidences that lipid metabolism is affected in numerous neurodegenerative diseases including Alzheimer’s disease. These dysfunctions lead to abnormal levels of certain lipids in the brain, cerebrospinal fluid and plasma. It is consequently of interest to establish lipid profiles in neurodegenerative diseases. This approach, which can contribute to identify lipid biomarkers of Alzheimers' disease, can also permit to identify new therapeutic targets. It was therefore of interest to focus on central and peripheral biomarkers in Alzheimer's disease. Methods: A review of the literature on 148 papers was conducted. Based on this literature, the involvement of lipids (cholesterol and oxysterols, fatty acids, phospholipids) in Alzheimer's disease has been proposed. Results: Of the 148 references cited for lipid biomarkers for Alzheimer's disease, 65 refer to cholesterol and oxysterols, 35 to fatty acids and 40 to phospholipids. Among these lipids, some of them such as 24S-hydroxyckolesterol, open up new therapeutic perspectives in gene therapy, in particular. The results on the very long-chain fatty acids suggest the potential of peroxisomal dysfunctions in Alzheimer's disease. As for the phospholipids, they could constitute interesting biomarkers for detecting the disease at the prodromal stage. Conclusion: There are now several lines of evidence that lipids play fundamental roles in the pathogenesis of AD and that some of them have a prognostic and diagnosis value. This may pave the way for the identification of new therapeutic targets, new effective drugs and / or new treatments.

Published
2018

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

Author

El Mostafa Karym, Meryam Debbabi, Michel Prost, Maryem Bezine, Randa Sghaier, Anne Vejux, Gérard Lizard, Stéphane Grégoire, Wiem Meddeb, Philippe Durand, Lucy Martine, Amira Zarrouk, Lionel Bretillon, Boubker Nasser, Thomas Nury, Asmaa Badreddine, Thibault Moreau, Mustapha Cherkaoui-Malki, Emmanuelle Prost-Camus, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Hassan 1er [Settat], Université de Monastir - University of Monastir (UM), Faculté de médecine de Sousse [Ibn EL Jazzar], Institut préparatoire aux études scientifiques et techniques [La Marsa] (IPEST), Université de Sousse, Laboratoire des Venins et Biomolécules Thérapeutiques - Laboratory of Venoms and Therapeutic Biomolecules (LR11IPT08), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Laboratoire de Recherche Appliquée Spiral [Bourgogne] (LARA SPIRAL), Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), This work was supported by grants from: University of Bourgogne (Dijon, France), University of Monastir (Monastir, Tunisia), Aides et Services à Domicile (ASSAD) (Louhans, France) and the Association Bourguignonne pour les Aplications en Sciences de l’Information en Médecine (ABASIM, Dijon, France). This work was supported by the Action Intégrée of the Comité Mixte Inter-Universitaire Franco-Marocain (CMIFM, MA/14/310) from the Projet Hubert Curien (PHC) Volubilis/Toubkal program, the Ministère de l’Enseignement Supérieur and the Centre National Pour la Recherche Scientifique et Technique (CNRST, Morocco), the projet PPR from the (CNRST, Morocco), the Ministère des Affaires Etrangères, the Conseil Régional de Bourgogne, and the University of Bourgogne. We also thank Philip Bastable for English corrections (University Hospital, Dijon, France)., Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] ( BIO-PEROXIL ), Université de Bourgogne ( UB ) -Université Bourgogne Franche-Comté ( UBFC ), Nutrition, Aliments Fonctionnels et Santé Vasculaire, Université de Monastir ( UM ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Recherche Appliquée Spiral [Bourgogne] ( LARA SPIRAL ), Modélisation mathématique et numérique ( M2N ), Conservatoire National des Arts et Métiers [CNAM] : EA7340, UMR 6578 : Adaptabilité Biologique et Culturelle ( UAABC ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Laboratoire de Biochimie et Neurosciences [Settat, Maroc], Faculté des Sciences et Techniques de Settat-Université Hassan I [Maroc], University of Bourgogne (Dijon, France) University of Monastir (Monastir, Tunisia) Aides et Services a Domicile (ASSAD) (Louhans, France) Association Bourguignonne pour les Aplications en Sciences de l'Information en Medecine (ABASIM, Dijon, France) Action Integree of the Comite Mixte Inter-Universitaire Franco-Marocain (CMIFM) from the Projet Hubert Curien (PHC) Volubilis/Toubkal program MA/14/310 Ministere de l'Enseignement Superieur Centre National Pour la Recherche Scientifique et Technique (CNRST, Morocco) projet PPR from the (CNRST, Morocco) Ministere des Affaires Etrangeres Conseil Regional de Bourgogne University of Bourgogne, and Lizard, Gérard

Subjects
MESH: Plant Oils/pharmacology, Antioxidant, argan oil, extra virgin olive oil, alpha-tocopherol, 7-ketocholesterol, mitochondria, lysosome, peroxisome, oxiapoptophagy, 158N murine, oligodendrocytes, assay interference compounds, polyunsaturated fatty-acids, smooth-muscle-cells, blood-brain-barrier, pear seed oil, alzheimers-disease, docosahexaenoic acid, mediterranean diet, multiple-sclerosis, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Antioxidants/pharmacology, Apoptosis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Antioxidants, MESH: Lipid Peroxidation, lcsh:Chemistry, Lipid peroxidation, Mice, MESH: Oligodendroglia/drug effects, MESH: Animals, MESH: Oxidative Stress/drug effects, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, General Medicine, régime méditerranéen, α-tocopherol, 158N murine oligodendrocytes, 3. Good health, maladie d'alzheimer, mitochondrie, MESH: Lysosomes/drug effects, Article, Inorganic Chemistry, 03 medical and health sciences, food, huile d'olive vierge, acide gras polyinsaturé, Food and Nutrition, sclérose en plaques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, tocopherol, huile d'argan, MESH: Cell Line, Tyrosol, MESH: Ketocholesterols/toxicity, 030104 developmental biology, chemistry, MESH: Mitochondria/drug effects, barrière hematoencephalique, Lipid Peroxidation, 0301 basic medicine, Argan oil, medicine.disease_cause, chemistry.chemical_compound, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Ketocholesterols, 2. Zero hunger, MESH: Peroxisomes/drug effects, Computer Science Applications, Oligodendroglia, Neuroprotective Agents, Biochemistry, Docosahexaenoic acid, Alimentation et Nutrition, Polyunsaturated fatty acid, food.ingredient, MESH: Apoptosis/drug effects, Context (language use), Biology, Catalysis, Cell Line, Peroxisomes, medicine, Animals, Plant Oils, Physical and Theoretical Chemistry, MESH: alpha-Tocopherol/pharmacology, MESH: Mice, MESH: Neuroprotective Agents/pharmacology, Organic Chemistry, Oxidative Stress, lcsh:Biology (General), lcsh:QD1-999, Lysosomes, Oxidative stress
Abstract

PMCID: PMC5666899; International audience; 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 mu M; 24 h) without and with argan oil (0.1% v/v) or -tocopherol (400 mu M, 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, beta-amyrin and citrostadienol alpha- and gamma-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.

Published
2017

7. Nopal Cactus (Opuntia ficus-indica) as a Source of Bioactive Compounds for Nutrition, Health and Disease

Author

Joseph Vamecq, Asmaa Badreddine, Norbert Latruffe, Gérard Lizard, Youssef El Kharrassi, Karym El-Mostafa, Boubker Nasser, Pierre Andreoletti, M'Hammed Saïd El Kebbaj, and Mustapha Cherkaoui-Malki

Subjects
Opuntia ficus-indica, Opuntia ficus, Anti-Inflammatory Agents, Pharmaceutical Science, Disease, Review, Health benefits, Biology, Antioxidants, Analytical Chemistry, lcsh:QD241-441, lcsh:Organic chemistry, Drug Discovery, Botany, cell signaling, Animals, Humans, Physical and Theoretical Chemistry, anti-inflammatory, chemistry.chemical_classification, PEAR, Plant Extracts, Organic Chemistry, Opuntia, Polyphenols, chemistry, Chemistry (miscellaneous), Cactus, Molecular Medicine, Extraction methods, Drug Screening Assays, Antitumor, Polyunsaturated fatty acid
Abstract

Opuntia ficus-indica, commonly referred to as prickly pear or nopal cactus, is a dicotyledonous angiosperm plant. It belongs to the Cactaceae family and is characterized by its remarkable adaptation to arid and semi-arid climates in tropical and subtropical regions of the globe. In the last decade, compelling evidence for the nutritional and health benefit potential of this cactus has been provided by academic scientists and private companies. Notably, its rich composition in polyphenols, vitamins, polyunsaturated fatty acids and amino acids has been highlighted through the use of a large panel of extraction methods. The identified natural cactus compounds and derivatives were shown to be endowed with biologically relevant activities including anti-inflammatory, antioxidant, hypoglycemic, antimicrobial and neuroprotective properties. The present review is aimed at stressing the major classes of cactus components and their medical interest through emphasis on some of their biological effects, particularly those having the most promising expected health benefit and therapeutic impacts.

Published
2014

8. Comparison of the effects of major fatty acids present in the Mediterranean diet (oleic acid, docosahexaenoic acid) and in hydrogenated oils (elaidic acid) on 7-ketocholesterol-induced oxiapoptophagy in microglial BV-2 cells

Author

Gérard Lizard, Wiem Meddeb, Mohamed Hammami, Stéphane Guyot, Sofien Ben-Hammou, Randa Sghaier, Amira Zarrouk, El Mostafa Karym, Boubker Nasser, Mondher Mejri, Thomas Nury, Asmaa Badreddine, Mohammad Samadi, Maryem Bezine, Mustapha Cherkaoui-Malki, Meryam Debbabi, Lionel Bretillon, Laboratoire Bio-PeroxIL. Biochimie du peroxysome, inflammation et métabolisme lipidique [Dijon] (BIO-PEROXIL), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Sousse, Laboratoire des Venins et Toxines, Institut Pasteur de Tunis, Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Faculté des Sciences de Bizerte [Université de Carthage], Université de Carthage - University of Carthage, Université Hassan 1er [Settat], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Procédés Microbiologiques et Biotechnologiques (PMB), Procédés Alimentaires et Microbiologiques (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes (LCP-A2MC), Université de Lorraine (UL), Université de Monastir - University of Monastir (UM), Univ. Bourgogne (Dijon, France) Univ. Monastir (Monastir, Tunisia) Univ. El Manar (Tunis, Tunisia) Univ. Bizerte (Bizerte, Tunisie) ASSAD (Louhans, France) Department of Neurology Action Integree of the Comite Mixte Inter-universitaire Franco-Marocain (CMIFM) from the PHC Volubulis/Toubkal program, Ministere des Affaires Etrangeres AIMA/10/238 Conseil Regional de Bourgogne, Faculté des Sciences de Bizerte, Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
0301 basic medicine, lipid droplets, Apoptosis, Cell Count, Oleic Acids, medicine.disease_cause, Diet, Mediterranean, Biochemistry, Lipid peroxidation, chemistry.chemical_compound, Mice, Lipid droplet, Membrane fluidity, oxidative stress, alzheimers-disease, calcium increase, Ketocholesterols, 2. Zero hunger, Chemistry, Fatty Acids, Elaidic acid, Docosahexaenoic acid, Microglia, macular degeneration, Docosahexaenoic Acids, Cell Line, 03 medical and health sciences, Structure-Activity Relationship, alpha-tocopherol, medicine, Autophagy, Animals, Molecular Biology, Cell Proliferation, Oxiapoptophagy, Dose-Response Relationship, Drug, Cholesterol, cholesterol oxidation, Organic Chemistry, Cell Biology, cognitive decline, 7-Ketocholesterol, cerebrospinal-fluid, Oleic acid, 158n murine oligodendrocytes, 030104 developmental biology, Oleic acid docosahexaenoic acid, Murine microglial BV-2 cells, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Oxidative stress, Oleic Acid
Abstract

International audience; Increased levels of 7-ketocholesterol (7KC), which results mainly from cholesterol auto-oxidation, are often found in the plasma and/or cerebrospinal fluid of patients with neurodegenerative diseases and might contribute to activation of microglial cells involved in neurodegeneration. As major cellular dysfunctions are induced by 7KC, it is important to identify molecules able to impair its side effects. Since consumption of olive and argan oils, and fish is important in the Mediterranean diet, the aim of the study was to determine the ability of oleic acid (OA), a major compound of olive and argan oil, and docosahexaenoic acid (DHA) present in fatty fishes, such as sardines, to attenuate 7KC-induced cytotoxic effects. Since elaidic acid (EA), the trans isomer of OA, can be found in hydrogenated cooking oils and fried foods, its effects on 7KC-induced cytotoxicity were also determined. In murine microglial BV-2 cells, 7KC induces cell growth inhibition, mitochondrial dysfunctions, reactive oxygen species overproduction and lipid peroxidation, increased plasma membrane permeability and fluidity, nuclei condensation and/or fragmentation and caspase-3 activation, which are apoptotic characteristics, and an increased LC3-II/LC3-I ratio, which is a criterion of autophagy. 7KC is therefore a potent inducer of oxiapoptophagy (OXIdation + APOPTOsis + autoPHAGY) on BV-2 cells. OA and EA, but not DHA, also favor the accumulation of lipid droplets revealed with Masson's trichrome, Oil Red O, and Nile Red staining. The cytotoxicity of 7KC was strongly attenuated by OA and DHA. Protective effects were also observed with EA. However, 7KC-induced caspase-3 activation was less attenuated with EA. Different effects of OA and EA on autophagy were also observed. In addition, EA (but not OA) increased plasma membrane fluidity, and only OA (but not EA) was able to prevent the 7KC-induced increase in plasma membrane fluidity. Thus, in BV-2 microglial cells, the principal fatty acids of the Mediterranean diet (OA, DHA) were able to attenuate the major toxic effects of 7KC, thus reinforcing the interest of natural compounds present in the Mediterranean diet to prevent the development of neurodegenerative diseases.

Published
2016

9. An expeditious synthesis of spinasterol and schottenol, two phytosterols present in argan oil and in cactus pear seed oil, and evaluation of their biological activities on cells of the central nervous system

Author

Mustapha Cherkaoui Malki, Gérard Lizard, Asmaa Badreddine, Amira Zarrouk, El Mostafa Karym, Youssef El Kharrassi, Boubker Nasser, Thomas Nury, Mohammad Samadi, Laboratoire Bio-PeroxIL. Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique ( Bio-PeroxIL ), Université de Bourgogne ( UB ), Université Hassan 1er ( UH1 ), Univ. Hassan I Settat, UR12ES05, Laboratory of Nutrition-Functional Food & Vascular Health, Faculté de Médecine de Monastir [Tunisie], Laboratoire de Biochimie, Faculté des Sciences et Techniques de Settat, Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes ( LCP-A2MC ), and Université de Lorraine ( UL )

Subjects
Central Nervous System, food.ingredient, Crystal violet test, Clinical Biochemistry, Stigmasterol, [ PHYS.COND.CM-MS ] Physics [physics]/Condensed Matter [cond-mat]/Materials Science [cond-mat.mtrl-sci], Argan oil, Organic synthesis, Biology, Biochemistry, Cell Line, Ferulic acid, Pyrus, chemistry.chemical_compound, Mice, Endocrinology, food, Schottenol, Cytotoxic T cell, Animals, Humans, Plant Oils, Molecular Biology, Spinasterol, Cell Proliferation, Pharmacology, PEAR, MIT test, Cell growth, Organic Chemistry, Phytosterols, Nervous cells, Sitosterols, Mitochondria, Rats, chemistry, Cactus, Seeds
Abstract

International audience; Spinasterol and schottenol, two phytosterols present in argan oil and in cactus pear seed oil, were synthesized from commercially available stigmasterol by a four steps reactions. In addition, the effects of these phytosterols on cell growth and mitochondrial activity were evaluated on 158N murine oligodendrocytes, C6 rat glioma cells, and SK-N-BE human neuronal cells with the crystal violet test and the MTT test, respectively. The effects of spinasterol and schottenol were compared with 7-ketocholesterol (71CC) and ferulic acid, which is also present in argan and cactus pear seed oil. Whatever the cells considered, dose dependent cytotoxic effects of 71CC were observed whereas no or slight effects of ferulic acid were found. With spinasterol and schottenol, no or slight effects on cell growth were detected. With spinasterol, reduced mitochondrial activities (30-50%) were found on 158N and C6 cells; no effect was found on SK-N-BE. With schottenol, reduced mitochondrial activity were revealed on 158N (50%) and C6 (10-20%) cells; no effect was found on SK-N-BE. Altogether, these data suggest that spinasterol and schottenol can modulate mitochondrial activity and might therefore influence cell metabolism.

Published
2015

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