Monograph amr

Argan Dom Guillaume, PhD; Zoubida Charrouf, PhD

Introduction Argan oil has sky-rocketed from a mere spinosa – Argan tree and seeds tourist attraction to one of the most prized in the world in a few short years. Argan oil’s unique savor and multiple pharmaco- logical properties are responsible for this success. Argan oil is almost exclusively produced in southwestern , one of the poorest parts of the country, where all-women cooperatives specialize in high quality argan oil extraction. !is activity is therefore providing a welcome "nancial stream. However, the argan tree, the fruit of which provides argan oil, could rapidly become an endangered species due to years of recurrent drought, forest overuse, and poor forest management. Consequently, such as the use of electric screw-presses, have women cooperatives aimed at sustainably support- allowed the discontinuation of the hand-malaxing ing the argan forest represent the cornerstone of a step, resulting in as much as 60-percent extraction vast program involving the reforestation of fragile yield.3 Even more recent technology permits the and particularly degraded lowlands and also large-scale production of virgin4 argan oil, without provide education of rural women. denaturing its quality,5 while preserving the 6 Argan Tree and Argan Oil sustainable development of the argan forest. Argan oil is principally produced as edible and !e argan tree (Argania spinosa (L.) Skeels; beauty grades. A third grade referred to as cosmetic Sapotaceae) is a slow-growing tree exclusively oil also exists. Virgin edible argan oil is prepared Dom Guillaume, PhD – School endemic to the barren lands of southwest of Medicine-Pharmacy, from slightly and carefully roasted kernels.7 It is Morocco.1 It is currently considered a relic of the University of Reims copper-colored, presents a slight taste, Champagne-Ardenne, Reims, tertiary era and is the only member of the and is the basic ingredient of the Amazigh diet.8 France. Sapotaceae family of plants whose distribution is Correspondence address: Virgin beauty argan oil, that is prepared from not intertropical. !e argan forest, which covers Departement of Medicinal unroasted kernels, is golden-colored and has no Chemistry, 51 rue Cognacq Jay, about 8,280 km2, was declared a Biosphere Reserve taste. Virgin edible argan oil presents a better 51100 Reims, France. by UNESCO in 1998. Traditionally, Amazigh (argan Email: dominique. long-term preservation pro"le than virgin beauty forest native) women used the kernels of argan [email protected] argan oil. At 25°C, the former preserves its quality fruit stones as a source of edible oil. Oil extraction for up to two years, while the shelf life of the latter Zoubida Charrouf, PhD – requires a tedious multistep process that begins University MohammedV- is only 3-4 months.9 Virgin edible and beauty argan with careful fruit drying2 and involves prolonged Agdal, Morocco; oils are produced in Moroccan women cooperatives, professor, Laboratory of Plant hand-malaxing of an aqueous argan kernel dow,3 and their world-wide marketing actively contrib- Chemistry with an extraction yield up to 35 percent. utes to the argan forest sustainable development. Improvements in argan oil extraction methodology,

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Key words: argan oil, Cosmetic argan oil is industrially prepared, mostly Tocopherols are molecules with strong antioxi- Argania spinosa, , in Europe, by solvent extraction of imported dant and free radical scavenging properties. monounsaturated , kernels. Cosmetic argan oil is only used as an gamma-Tocopherol, the most e%cient free radical MUFA, sebum, cholesterol, 16 hyperlipidemia, diabetes, ingredient for the preparation of shampoos, scavenger of all tocopherols, composes 69 percent antiproliferative, cancer, , and industrial cosmetic products.10 of argan oil total tocopherol content.15 Because cosmetic Traditionally, argan oil was used extensively in tocopherols and sterols can act synergistically, the Morocco as a topical oil to treat various ailments, speci"c combination of molecules found in the such as dry skin, acne, psoriasis, eczema, wrinkles, unsaponi"able matter is theorized to contribute to joint pain, and skin in#ammation.11 It is also used the therapeutic aspects of argan oil.17 to prevent hair loss and dry hair.11 Ingested, argan oil is a choleretic and hepatoprotective agent that Mechanisms of Action/Clinical Activity can prevent hypercholesterolemia and Topical and oral argan oils have di$erent atherosclerosis.11 therapeutic properties (Figure 1). Cosmetic properties attributed to topical (beauty) oil are Biochemical Constituents primarily based on traditional claims and have Virgin argan oil of edible or beauty grade is little scienti"c backing. Properties of virgin edible composed of 99-percent acylglycerides (primarily argan oil have been evaluated in animal models and triglycerides).11 Unsaponi"able matter, which human cohort studies. represents the remaining one percent, is composed of carotenes, tocopherols, triterpene alcohols, Anti-sebum Activity sterols, and xanthophylls.11 Fatty acids that Argan oil-containing creams are frequently compose acylglycerides are principally oleic and indicated in cosmetology as moisturizing, , 43-49 percent and 29-36 percent, respectively.12 Oleic acid is a monounsaturated fatty acid of the Figure 1. Therapeutic Properties of Argan Oil omega-9 family, while linoleic acid is a polyunsaturated fatty acid belonging to the omega-6 family. Palmitic and are saturated fatty acids W found at a concentrations of 11-15 ound healer percent and 4-7 percent, respectively.12 Moisturizing Some argan oil pharmacological properties are likely to result from its high unsaturated fatty acid content. Oleic acid, a monounsaturated fatty Anti-acne acid, has numerous therapeutic e$ects13 that contribute to the impor- Anti-aging tant properties of argan oil. Because a Anti-sebum linoleic acid de"ciency can induce poor BEAUTY wound healing,14 the high linoleic acid content of argan oil may contribute to e EDIBLE its traditional indication as a cure for tiv Choleretic skin in#ammation. However, several Hepatoprotec other oils are rich in oleic and/or

linoleic acid but do not possess the e Anti- same therapeutic e$ects. Many of obesit argan oil’s speci"c health bene"ts are diabetic attributed to its composition of Anti- y unsaponi"able matter (although it constitutes a small amount of the oil) and high tocopherol content.15 !e tocopherol content of argan oil is 620 Anti-proliferativ mg/kg, compared to 320 mg/kg in .

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anti-aging, and repair creams. !e anti-sebum signal-regulated kinases 1 and 2 (ERK1/2) to activity of topical argan oil was demonstrated on respond to increasing doses of insulin, while the 20 17- to 50-year-old volunteers with oily facial response to serine/threonine kinase (Akt) skin. Sebum level was determined on forehead and remained undisturbed.25 Argan oil polyphenols also both cheeks. A twice daily facial application of an interrupt the insulin-signaling cascades at the argan oil-containing cream for four weeks revealed MEK1/2-ERK1/2 interface.25 signi"cant anti-sebum activity that translated to reduced greasiness and improved appearance of Cardiovascular/Lipid E!ects oily facial skin.18 Treatments longer than four Phenolics26 and phytosterols27 possess direct or weeks did not show improved sebum-regulating indirect hypocholesterolemic activity. Rat studies e%cacy. demonstrate the hypolipidemic and hypotriglyceri- demic e$ect of argan oil.28 Another study showed Antiproliferative Activity/Cancer Preventive that the phenolic fraction of argan oil prevents Epidemiological data have indicated that regular low-density lipoprotein (LDL) cholesterol oxidation consumption of edible olive oil could have signi"- in isolated human plasma and enhances reverse cant protective e$ects against colorectal, breast, cholesterol transport by increasing high-density prostate, pancreas, and endometrial cancer.19 !e lipoprotein (HDL) cholesterol levels.29 combined presence in olive oil of oleic acid, pheno- A human cohort study provides evidence for the lics endowed with antioxidant properties, and hypolipidemic activity of argan oil.30 During this squalene is currently considered to be the key strict lipid-controlled study, 60 men were "rst fed factor to explain this antiproliferative activity.20 25 g/day of on toasted bread as a source of Because argan and olive oils have these essential lipids for two weeks in order to establish baseline constituents in common, an antiproliferative e$ect conditions. !en, butter was replaced by 25 mL/ has been claimed for argan oil.21 day of virgin argan oil for one half of the group, !e antiproliferative activity of argan oil unsa- while the other half received the same amount of poni"able matter, mainly polyphenols, tocopherols, virgin olive oil; otherwise, a similar diet was given and sterols, has been studied in vitro on hormone- to both groups. After three weeks, participants independent (DU145 and PC3), hormone-depen- underwent medical examination and parameters dent (LNCaP), and SV40-immortalized prostate such as body mass index (BMI), systolic and tumor cell lines.22,23 Sterols from argan oil appear diastolic blood pressure (SBP and DBP, respec- to have particularly strong antiproliferative activity tively), serum total cholesterol, HDL, LDL, apolipo- against PC3 cell line; whereas, polyphenols display proteins A-I and B, and triglyceride levels were a high activity against DU145 and LNCaP cell lines. measured and compared with baseline values. BMI, !e precise mechanism of action as an antiprolif- SBP, DBP, and total cholesterol levels did not erative agent is still poorly understood. Cell cycle signi"cantly change during the three-week study. arrest mediated by up-regulation of the P27 cell In the argan oil group, HDL cholesterol and cycle regulatory protein may explain the speci"c triglyceride levels signi"cantly increased and activity of argan oil polyphenols. Inhibition of decreased, respectively. Conversely, signi"cant ornithine decarboxylase or nitric oxide synthase, decreases in LDL cholesterol and apolipoprotein-B two enzymes overexpressed in prostate cancer, (apo-B) were observed only in the olive oil group.30 could also be involved in the observed activity of !e impact of argan oil consumption on oxida- polyphenols.23 Saponins from argan press-cake, the tive stress plasma markers and HDL paraoxonase 1 residue remaining after argan kernel pressing, also (PON1) activity has been evaluated. !is study is have antiproliferative e$ects on DU145, LNCaP, the "rst of its kind to provide sound evidence for and PC3 cell lines.23,24 However, these saponins, the potential antiatherogenic activity of argan oil.31 which are water-soluble compounds, have not been After three weeks of daily argan oil consumption identi"ed in argan oil. (25 mL/day), plasma PON1 activity, antioxidant Studies using HT-1080 "brosarcoma and vitamins, and LDL susceptibility to oxidation were MSV-MDCK-invasive cells have con"rmed the measured.31 A signi"cant increase in PON1 activity antiproliferative activity of argan oil polyphenols.25 and bene"cial e$ects on plasma lipid peroxide, Using hepatoma tissue culture cells, the squalene conjugated dienes, and vitamin E concentration and polyphenol-rich extract of argan oil has been were observed. !is was supported by an in vitro shown to reduce the ability of extracellular increase in resistance of LDL cholesterol to

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copper-induced oxidation. !e antioxidant compo- glycemia reduction was observed after 15 days. nent of argan oil, composed of polyphenols, Argan oil also signi"cantly decreased the amount of tocopherols, and sterols, is suspected to be absorbed glucose in the jejunum segment. In a involved in this antiatherosclerotic activity.31 recent rat experiment, the antihyperglycemic e$ect A second cohort study con"rmed the antioxidant of argan oil was further con"rmed, while no change and hypocholesterolemic properties of argan oil.32 in blood glucose levels was observed for normogly- !e study was conducted on 96 subjects, 62 of cemic fasted rats.38 whom were regular argan oil consumers (15 g/day). !e other subjects received their lipids from an Side E!ects and Toxicity unknown source. Signi"cantly lower LDL choles- Argan oil has been used in Morocco as food and terol and apo-B levels were observed in argan oil applied to the skin for centuries; there are cur- consumers compared to non-consumers. rently no known acute or chronic toxicity levels. Lipoprotein(a) concentrations were also lower in One case of anaphylaxis has been reported.39 the argan oil group. Because of the observed concomitantly high plasma vitamin E levels, the Dosage antioxidant e$ects may be responsible. However, !erapeutic doses to prevent metabolic diseases no signi"cant di$erences were observed in thiobar- range from 15-30 g (1-2 tablespoons) uncooked bituric acid reactive substances that are a common argan oil per day, with maintenance dosing of 3-6 g index to evaluate lipid peroxidation. Altogether, daily. Argan oil can be used as a salad dressing or these results suggest a bene"cial impact of argan added to dishes after cooking. It enhances the oil consumption to prevent coronary artery disease #avor of ethnic food. Although argan oil should not in humans, even though the precise metabolic be used for prolonged frying, it is appropriate for pathways involved are not yet fully elucidated.33 short-time frying.40 Finally, argan oil improves endothelial function in hypertensive rats.34 It also inhibits platelet References aggregation by acting on the attachment of 1. Morton JF, Voss GL. !e argan tree (Argania "brinogen to GIIb/IIIa platelet receptors without sideroxylon, Sapotaceae), a desert source of edible oil. a$ecting the adhesiveness of platelets to the Econ Bot 1987;41:221-233. vascular endothelium. Rat studies were performed 2. Harhar H, Gharby S, Kartah BE, et al. Long argan in vitro or in vivo. In vitro, argan oil prevents fruit drying time is detrimental for argan oil quality. thrombin- or epinephrine-induced platelet aggre- Nat Prod Commun 2010;5:1799-1802. gation. In vivo, a similar activity was observed, 3. Charrouf Z, Guillaume D. Argan oil, functional food, while platelet concentration remained unchanged. and the sustainable development of the argan forest. Argan oil can reduce platelet aggregation, therefore Nat Prod Commun 2008;3:283-288. minimizing the risk of thrombosis in cardiovascu- 4. Matthäus B, Spener F. What we know and what we lar events.35 should know about virgin oils – a general introduc- tion. Eur J Lipid Sci Technol 2008;110:597-601. Antidiabetic Activity 5. Matthäus B, Guillaume D, Gharby S, et al. E$ect of Antidiabetic activity of argan oil has been processing on the quality of edible argan oil. Food demonstrated in animals. An oral glucose tolerance Chem 2010;120:426-432. test was performed on healthy and diabetic rats. 6. Charrouf Z, Guillaume D. Sustainable development Intraperitoneal administration of argan oil (2.5 in Northern Africa: the argan forest case. mL/kg) 30 minutes before glucose loading induced Sustainability 2009;1:1012-1022. DOI:10.3390/ signi"cant blood sugar reduction that lasted for su1041012 three hours.36 Comparison of the metabolic 7. Harhar H, Gharby S, Kartah B, et al. In#uence of response of rats to a free-access, high /high argan kernel roasting-time on virgin argan oil glucose diet in which six percent of the fat was composition and oxidative stability. Plant Foods replaced by either argan oil or "sh oil showed that Hum Nutr 2011;66:163-168. DOI: 10.1007/ both oils resulted in the restoration of insulin s11130-011-0220-x signaling in fat and liver cells, but only "sh oil 8. Charrouf Z, Guillaume D. Should the Amazigh diet restored systemic insulin sensitivity.37 (regular and moderate argan-oil consumption) have When streptozotocin-induced diabetic rats were a bene"cial impact on human health? Crit Rev Food orally fed with argan oil (2 mL/kg), a signi"cant Sci Nutr 2010;50:473-477.

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9. Gharby S, Harhar H, Guillaume D, et al. 21. Khallouki F, Younos C, Soulimani R, et 31. Cherki M, Derouiche A, Drissi A, et al. Oxidative stability of edible argan oil: a al. Consumption of argan oil (Morocco) Consumption of argan oil may have an two year study. LWT-Food Sci Technol with its unique pro"le of fatty acids, antiatherogenic e$ect by improving 2011;44:1-8. tocopherols, squalene, sterols and paraoxonase activities and antioxidant 10. Charrouf Z, Guillaume D. Argan oil and phenolic compounds should confer status: intervention study in healthy other argan products; use in dermocos- valuable cancer chemopreventive men. Nutr Metab Cardiovasc Dis metology. Eur J Lipid Sci Technol e$ects. Eur J Cancer Prev 2003;12:67-75. 2005;15:352-360. 2011;113:403-408. 22. Bennani H, Drissi A, Giton F, et al. 32. Drissi A, Girona J, Cherki M, et al. 11. Charrouf Z, Guillaume D. Antiproliferative e$ect of polyphenols Evidence of hypolipemiant and Ethnoeconomical, ethnomedical and and sterols of virgin argan oil on human antioxidant properties of argan oil phytochemical study of Argania spinosa prostate cancer cell lines. Cancer Detect derived from the argan tree (Argania (L.) Skeels. J Ethnopharmacol Prev 2007;31:64-69. spinosa). Clin Nutr 2004;23:1159-1166. 1999;67:7-14. 23. Drissi A, Bennani H, Giton F, et al. 33. Cherki M, Berrougui H, Drissi A, et al. 12. Rahmani M. !e chemical composition Tocopherols and saponins derived from Argan oil: which bene"ts on cardiovas- of virgin argan oil. Agricultures Argania spinosa exert an antiprolifera- cular diseases? Pharmacol Res 2005;14:461-465. tive e$ect on human prostate cancer. 2006;54:1-5. 13. Lopez-Huertas E. Health e$ects of oleic Cancer Invest 2006;24:588-592. 34. Berrougui H, Alvarez de Sotomayor M, acid and long chain omega-3 fatty acids 24. Bennani H. Impact of argan oil on Pérez-Guerrero C, et al. Argan (Argania (EPA and DHA) enriched milks. A prostate cancer. Techno Lab 2007;6:8-10. spinosa) oil lowers blood pressure and review of intervention studies. [Article in French] improves endothelial dysfunction in Pharmacol Res 2010;61:200-207. 25. Samane S, Noël J, Charrouf Z, et al. spontaneously hypertensive rats. Br J 14. Galli C, Calder PC. E$ects of fat and Insulin-sensitizing and anti-prolifera- Nutr 2004;92:921-929. fatty acid intake on in#ammatory and tive e$ects of Argania spinosa seed 35. Mekh" H, Gadi D, Bnouham M, et al. immune responses: a critical review. extracts. Evid Based Complement Altern E$ect of argan oil on platelet aggrega- Ann Nutr Metab 2009;55:123-139. Med 2006;3:317-327. tion and bleeding time: a bene"cial 15. Charrouf Z, Guillaume D. Argan oil: 26. Nash SD, Nash DT. Nuts as part of a nutritional property. J Compl Integr Med occurrence, composition and impact on healthy cardiovascular diet. Curr 2008;5:18. human health. Eur J Lipid Sci Technol Atheroscler Rep 2008;10:529-535. 36. Bnouham M, Bellahcen S, Benalla W, et 2008;110:632-636. 27. !ompson GR, Grundy SM. History and al. Antidiabetic activity assessment of 16. Jiang Q, Christen S, Shigenaga MK, development of plant sterol and stanol Argania spinosa oil. J Compl Integr Med Ames BN. gamma-Tocopherol, the esters for cholesterol-lowering 2008;5:32. major form of vitamin E in the US diet, purposes. Am J Cardiol 2005;96:3D-9D. 37. Samane S, Christon R, Dombrowski L, deserves more attention. Am J Clin Nutr 28. Berrougui H, Ettaib A, Herrera et al. and argan oil intake 2001;74:714-722. Gonzalez MD, et al. Hypolipidemic and di$erently modulate insulin resistance 17. Monfalouti HE, Guillaume D, Denhez C, hypocholesterolemic e$ect of argan oil and glucose intolerance in a rat model Charrouf Z. !erapeutic potential of (Argania spinosa L.) in Meriones shawi of dietary-induced obesity. Metabolism argan oil: a review. J Pharm Pharmacol rats. J Ethnopharmacol 2003;89:15-18. 2009;58:909-919. 2010;62:1669-1675. 29. Berrougui H, Cloutier M, Isabel M, 38. Bellahcen S, Mekh" H, Ziyyat A, et al. 18. Dobrev H. Clinical and instrumental Khalil A. Phenolic-extract from argan Prevention of chemically induced study of the e%cacy of a new sebum oil (Argania spinosa L.) inhibits human diabetes mellitus in experimental control cream. J Cosmet Dermatol low-density lipoprotein (LDL) oxidation animals by virgin argan oil. Phytother 2007;6:113-118. and enhances cholesterol e&ux from Res 2011 May 17. [Epub ahead of print] 19. Trichopoulou A, Lagiou P, Kuper H, human THP-1 macrophages. DOI: 10.1002/ptr.3524. Trichopoulos D. Cancer and Atherosclerosis 2006;184:389-396. 39. Astier C, Benchad Yel A, Moneret- Mediterranean dietary traditions. 30. Derouiche A, Cherki M, Drissi A, et al. Vautrin DA, et al. Anaphylaxis to argan Cancer Epidemiol Biomarkers Prev Nutritional intervention study with oil. Allergy 2010;65:662-663. 2000;9:869-873. argan oil in man: e$ects on lipids and 40. Yaghmur A, Aserin A, Mizrahi T, et al. 20. Owen RW, Giacosa A, Hull WE, et al. apolipoproteins. Ann Nutr Metab Evaluation of argan oil for deep-fat Olive-oil consumption and health: the 2005;49:196-201. frying. Lebens-Wiss-Technol possible role of antioxidants. Lancet 2001;34:124-130. Oncol 2000;1:107-112.

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