PROFESSOR OF PHARMACOLOGY. FACULTY OF MEDICINE AND PHARMACY, UNIVERSITY SIDI MOHAMED BEN ABDELLAH, FEZ. MOROCCO. DIRECTOR RESEARCH LABORATORY OF MOLECULAR BASIS OF HUMAN PATHOLOGIES AND THERAPEUTIC TOOLS
Argan oil is produced from nuts of Argania Spinosa tree. It is highly enriched with bioactive substances such as tocopherols, carotenoïds, sterols and polyphenol molecules. Each of these classes of molecules was shown to exert antioxidant, anti-tumor and anti-inflammatory activities in isolated cells and/or animal experiments. However, clinical evidence for such activities are scarce, and the main data reported so far in clinical studies have focused on the ability of argan oil to regulate blood lipids and to improve the oxidative status in men. In the present review, I summarize some recent clinical and biochemistry results on the effects of Argan oil consumption, in particular, those studied in end-stage renal failure patients under hemodialysis and knee osteoarthritis patients. The main outcomes of Argan oil consumption are a significant improvement of blood lipids status, lipid atherogenic ratios, oxidative status, some metabolic syndrome components and pain scores. In light of the above biological and clinical effects of argan oil, some potentially therapeutic perspectives will be discussed.Argan oil “AO” is extracted from nuts of an endemic tree in the south-west of Morocco, called Argania Spinosa. For many centuries, the Amazigh/Berber population have used AO for culinary purposes, and also as a traditional cosmetic to moisturize and soften skin. Most importantly, AO has always been used as a traditional medicine for joint pain and many other health issues.
The chemical composition of AO has been studied thoroughly (1-5). AO is composed mainly of triglycerides (99%) that contains most of the fatty acids of AO, of whom, 80 % belong to the unsaturated category of fatty acids, such as oleic acid (45%) and linoleic acid (34%). The most abundant saturated fatty acid in AO is palmitic acid (12%).
According to intervention studies in many clinical trials on oleic acid containing culinary oils, or oleic acid-enriched oils (6), and also according to epidemiologic studies on Mediterranean dietary habits, in particular, consumption of olive oil (7-9), it was concluded that oleic acid was involved in the low incidence of cardiovascular events, hypertension, and stroke in man. These data support that AO could share many of the olive oil positive effects on human health through its oleic acid content.
Beside triglycerides (99%), the remaining 1% of the chemical composition of AO is made of several categories of molecules that are endowed with crucial biological activities, mainly the anti-oxidant one.
Such categories of molecules are tocopherols, carotenoïds, sterols, and polyphenols. Gamma-tocopherol (vitamin E) is the most abundant species of tocopherols found in AO (1-5). AO contains much more gamma-tocopherol (around 600 mg/Kg) than other oil species such as olive oil. Thanks to its vitamin E properties, gamma-tocopherol, along with carotenoïds, and polyphenol molecules are very active substances against oxygen free radical-induced oxidative stress in many cell species. They prevent molecular damage in many inflammatory, cardiovascular and neurodegenerative diseases.
The effect of polyphenol molecules on cell growth of healthy and tumor cells in cell tissue cultures experiments have shown that some of these molecules are endowed with anti-proliferative and antitumor properties (10). Argania spinosa seed extracts were shown to exert an anti-proliferative effect on cells in culture (11,12), which is in favor of a possible anti-tumor property of AO in man.
IMPROVEMENT OF BLOOD LIPID STATUS
Sterols in AO are represented by two major molecules, namely, schottenol (46%) and spinasterol (38%) (1-4). There is no clinical data on AO regarding these molecules; however, some phytosterols were reported as lipid – and cholesterol lowering molecules (13). Most of the clinical studies that were carried out on AO have focused on its effect on blood lipids and oxidative status. Several studies have shown that consumption of AO for several weeks can improve plasma lipid status in human (14-22). Recently, in a controlled randomized clinical study (18,19), that was carried out on end-stage renal failure patients undergoing hemodialysis, where most of them have abnormal lipid levels (high LDLc, low HDLc, high triglyceride). Compared to control patients, AO-treated patients have had an improvement of their plasma lipid status, and so, their atherogenic ratios (Cholestérol/HDL, TG/HDL, LDL/HDL et ApoB/ApoA). The above data are very relevant for cardiovascular protection in hemodialysis patients because in this category of patients, dyslipidemia is a risk factor for cardiovascular mortality (23,24). These patients also suffer from oxidative stress-associated harmful biochemical events, such a lipid peroxidation and protein- and nucleic acid-oxygen free radicals attacks, upon hemodialysis sessions (25,26). Targeting dyslipidemia and oxidative stress in these populations with AO should be a therapeutic tool along with other molecules such as other “lipid-lowering drugs” such as statins (27). The latter was a subject of hot debates among the scientific community these last years (28). In a controlled and cross-over clinical study on hemodialysis patients, AO consumption has proved to be effective in improving both oxidative stress status, vitamin E levels, and HDLc in a significant manner (20).
ARGAN OIL ON PAIN AND METABOLIC SYNDROME
A clinical study was carried out in order to check the effect of AO consumption on patients suffering from knee osteoarthritis. Most of the patients enrolled in the study were diagnosed with metabolic syndrome (21-22). Metabolic syndrome is declared in a given patient when at least three of the five following events are found: high waist circumference, high blood pressure, high triglyceride levels, high glycemia, low HDLc (29). Some of the metabolic components were described to be associated with knee pain (30). Pain, stiffness and walking difficulties were assessed by several tests (WOMAC, lesquennes index and visual analogic scale (30). AO consumption has alleviated pain in knee osteoarthritis patients (21). Scores of walking difficulties were also ameliorated in a significant manner (21). Interestingly, upon AO consumption, plasma lipid status and lipid atherogenic indices were ameliorated as well (21,22). A small but significant amelioration of blood pressure and glycemia were found in AO consumers, though, this effect should be confirmed in a large-scale study.
FUTURE AND PERSPECTIVES FOR ARGAN OIL.
Thanks to its special chemical composition, AO seems to be a perfect “cocktail” of bioactive compounds that are rarely found all together in the same plant extract. The above mentioned biologic effects in laboratory experiments, a well as those that were reported in clinical studies, should encourage other clinical studies on various clinical events where cholesterol, abnormal lipid status, metabolic syndrome, as well as oxidative stress are key factors as suggested here below (Figure 1).
AO contains a fair concentration of β-carotene (around 20 mg/Kg) (1). The presence of carotenoïds in AO was reported in a paper published in 1974 (31), to whom most recent papers have referred to, regarding carotenoïds content of AO, however, the presence of other carotenoïds in AO other than β- carotene, such as xanthophylls (lutein and zeaxanthin) have never been documented in AO. These pigment molecules are known to be present in olive oil (32) and in other yellowish plants, vegetables, and fruits. The hazelnut color of AO is supposed to be due to these carotenoïd pigments, although, in the process of culinary AO production, nuts roasting also darkens the original hazelnut color of AO, as compared to cosmetic AO whose production process does not involve nuts roasting. Xanthophylls are concentrated in the retina and are relevant for eye protection against UV light and cell damage caused by oxygen free radicals (33,34) . AO carotenoïds should be of special interest in the treatment of carotenoïds-deficient patients (33,34).
MEMORY AND COGNITIVE ISSUES IN NEURODEGENERATIVE DISEASES
It is known that cholesterol metabolism, as well as oxygen free radical-associated neuronal damage, are associated with mild cognitive impairment in early phases of Alzheimer disease (35-39). Plant sterols and antioxidant Vitamine E were suggested as possible treatments for mild cognitive impairment (40,41). Because AO has a special chemical composition, many of its lipophylic and anti-oxidant molecules (vitamin E, sterols, polyphenols, carotenoïds) can reach the brain cells and should provide a real synergistic molecular and cell protection against oxygen free radicals. Sterol molecules should be potentially able to interfere with cholesterol-associated plaque formation and its subsequent clinical consequences (39,40).
OXIDATIVE STRESS-ASSOCIATED MALE SUBFERTILITY
Sperm and spermatozoids are thought to be very sensitive to the aggressive environment, mainly the oxidative one. Although there is a lot of research work supporting antioxidant therapy against oxidative stress-associated spermatozoid cells damage (42), a meta-analysis on this issue supports partially possible treatment of oxidative stress-associated subfertility (43). In this regard, AO chemical composition is very pertinent, and most of its compounds are known as strong antioxidants and could fairly contribute to the protection against harmful oxidative stress-associated spermatozoid cells damage.
IONIZING RADIATION-ASSOCIATED CELL OXIDATIVE STRESS DAMAGES
It is known that exposure to ionizing radiation has potential oxidative effects on organisms. Examples of such events are exposures to a low dose of ionizing radiations or leak of radiations upon a nuclear facility accident. Many research works support the protective effects of antioxidants against radiation- associated oxidative stress (44). Interestingly, Vitamine A, Vitamine C, and vitamin E were shown to prevent chronic gamma radiation-associated inhibition of intestinal nutriments absorption in mice (45). Another study has shown that the phenolic compound, quercetin, has preventive and therapeutic effects on experimental radiation-induced lung injury in mice (46). From the above references, one could expect that through its high antioxidants content, AO could certainly bring possible biological effects against ionization-associated side effects in medicine.
BURN WOUND HEALING CAPACITY
Recently, laboratory experiments have shown that topical AO can significantly improve burn wound healing in rat (47). In this regard, olive oil efficacy on burn wounds was demonstrated both in clinical
and experimental studies (48,49). The above studies encourage clinical investigations on the potential of oral and topical use of AO on skin wounds healing.
SPECIAL INTEREST TO PROMOTE ARGAN TREE
Recently, Morocco has made Argan tree as a national priority, through the creation of an agency “l’Agence National pour le Développement des Zones Oasiennes et de l’Arganier (ANDZOA) (50) that promotes research on preservation of the argan tree, its oil and all of its byproducts. Looking forward to promoting clinical research on argan oil, a group of researchers in many medical specialties (nephrology, rheumatology, neurology, ophthalmology, endocrinology and pharmacology) at the University of Fez (Sidi Mohamed Ben Abdellah, faculty of medicine), are working on argan oil therapeutics in the frame of GRETHA (Groupe de Recherches sur les Effets Thérapeutiques de l’Huile d’Argane), in collaboration with other researchers from the universities of Rabat (Morocco) and Sevilla in Spain.
Acknowledgments: The author is very grateful to all patients who participated in the clinical trials. Thanks go to the personnel of medical services who are involved in the activity of the GRETHA (Groupe de Recherches sur les Effets Thérapeutiques de l’Huile d’Argane) at Fez University Hospital ” nephrology (Pr Tarik Sqalli Houssaini), rheumatology (Pr Taoufik Harzy), neurology (Pr Faouzi Belehsen) and ophthalmology (Pr Idriss Benatiya)” and at Rabat University Hospital ” nephrology of Mohamed V Military Hospital “Pr Driss El Kabbaj and Pr. Rachid El Jaoudi)”. Financial support from the University of Sidi Mohamed Ben Abdellah is gratefully acknowledged.