Plant Sources, Extraction Methods, and Uses of Squalene

Hindawi International Journal of Agronomy Volume 2018, Article ID 1829160, 13 pages https://doi.org/10.1155/2018/1829160 Review Article Plant Sources, Extraction Methods, and Uses of Squalene M. Azalia Lozano-Grande,1 Shela Gorinstein,2 Eduardo Espitia-Rangel,3 Gloria Da´vila-Ortiz ,4 and Alma Leticia Martıńez-Ayala 1 1Centro de Desarrollo de Productos Bióticos, Instituto Politécnico Nacional, San Isidro, 62731 Yautepec, MOR, Mexico 2Institute for Drug Research, School of Pharmacy, Hadassah Medical School, *e Hebrew University, Jerusalem 91120, Israel 3Instituto Nacional de Investigaciones Forestales, Agr´ıcolas y Pecuarias, Campo Experimental Valle de Me´xico, Coatlinchan, 56250 Texcoco, MEX, Mexico 4Instituto Politećnico Nacional, Escuela Nacional de Ciencias Biolo´gicas, Delegacioń Miguel Hidalgo, 11340 Ciudad de México, Mexico Correspondence should be addressed to Alma Leticia Mart´ınez-Ayala; [email protected] Received 2 March 2018; Accepted 28 May 2018; Published 1 August 2018 Academic Editor: Jose´ M. Alvarez-Suarez Copyright © 2018 M. Azalia Lozano-Grande et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Squalene (SQ) is a natural compound, a precursor of various hormones in animals and sterols in plants. It is considered a molecule with pharmacological, cosmetic, and nutritional potential. Scientific research has shown that SQ reduces skin damage by UV radiation, LDL levels, and cholesterol in the blood, prevents the suffering of cardiovascular diseases, and has antitumor and anticancer effects against ovarian, breast, lung, and colon cancer. +e inclusion of SQ in the human diet is recommended without causing health risks; however, its intake is low due to the lack of natural sources of SQ and efficient extraction methods which limit its commercialization. Biotechnological advances have developed synthetic techniques to produce SQ; nevertheless, yields achieved are not sufficient for global demand for industrial or food supplement purposes. +e effect on the human body is one of the scientific issues still to be addressed; few research studies have been developed with SQ from seed or vegetable sources to use it in the food sector even though squalene was discovered more than half a century ago. +e aim of this review is to provide an overview of SQ to establish research focus with special reference to plant sources, extraction methods, and uses. 1. Introduction +e use of marine animal oil as a source of SQ has been limited by animal protection regulations and the presence of Squalene is a linear triterpene synthesized in plants, animals, organic pollutants (POPs) as organochlorine pesticides, bacteria, and fungi as a precursor for the synthesis of sec- polycyclic aromatic hydrocarbons, dioxins, or heavy metals ondary metabolites such as sterols, hormones, or vitamins. It that cause cancer. +is has generated interest in finding new is a carbon source in the aerobic and anaerobic fermentation natural sources, especially of plant origin [6]. of microorganisms [1, 2]. Among the plant sources reporting SQ content are olive +e SQ was discovered by Tsujimoto Mitsumaru in 1916, oil (564 mg/100 g), soybean oil (9.9 mg/100 g), rice, wheat a Japanese researcher who described the compound as a highly germ, grape seed oil (14.1 mg/100 g), peanut (27.4 mg/100 g), unsaturated molecule, assigning its name to the genus from corn, and amaranth (5942 mg/100 g). Of these species, olive which was isolated, Squalus spp. [3, 4]. +e main source of SQ is only used for extracting commercial squalene despite the was the liver of marine animals rich in lipids and unsaponi- highest content reported for amaranth. fiable matter (50–80%), whose SQ content may comprise up to SQ is also found in the human body, is secreted by the 79% of the total oil. SQ is considered important in oily extract sebaceous glands for skin protection, and forms part of for the survival of deep-water animals, where oxygen supply is 10–15% of lipids on the skin surface in concentrations of poor and pressures are very high [5]. 300–500 µg/g and on internal organs such as the liver and 2 International Journal of Agronomy (a) (b) Figure 1: Linear (a) and ¢at trigonal (b) structure of squalene. small intestine in concentrations of less than 75 µg/g antioxidant eect of SQ in olive oil, where the antioxi- [3, 4, 7]. dant activity was weak in presence of other fatty acids, Several studies have conrmed the health benets of SQ possibly due to a competitive oxidation between the same in nutritional, medicinal, and pharmaceutical aspects. It is lipids of the extract. As an endogenous compound, the SQ considered a potent chemopreventive and chemotherapeutic also contributes to oxidative stability, but this has not agent, which inhibits the tumor growth in the colon, skin, lung, been completely studied. and breast, and it stimulates the immune system for the ap- plication of drugs in the treatment of diseases such as HIV, 3. Function of Squalene in Plants H1N1, leukemia, papilloma, and herpes, among others [8–11]. SQ-related research such as pharmaceutical, cosmetic, Plants biosynthesize a wide variety of metabolites ( 230 con- and food applications are issues that have been addressed stituents) in response to stress conditions due to drought, independently and do not address commercial expectations. predation, or disease. Among these metabolites, those> are the is review provides an overview of the potential natural fractions unsaponiable ( 1.5%) that contribute to bioactive sources and forms of extraction of this natural lipid. properties of oils and imparts stability to the cell membrane of plants [13, 19]. < 2. Physicochemical Characteristics of Squalene Unsaturated lipids are key components in cell membranes, and Biosynthesis which together with SQ can regulate biophysical properties, diusion, and dynamic membrane organization. Models of cell e SQ (2,6,10,15,19,23-hexamethyl-6,6,10,14,18,20-tetracosahexane) membranes have suggested that SQ acts in the lipid bilayer with is a hydrocarbon chain formed by six isoprene units (Figure 1); other fatty acids as inhibitors of proton leakage in alkaline when the units are assembled, they form a triterpene that membranes and in¢uence in the synthesis of ATP [12]. gives the lipid character. e six carbon double bonds (C C) By its nonpolar nature, the SQ is located on the hydro- allow the molecule to be one of the most unsaturated lipids, and phobic center of the lipid bilayer, organized in a spiral or it is sensitive to oxidation [12]. extended conformation, oriented in parallel to the phospho- e SQ is physically a transparent oil with the molec- lipid chains between the cell membrane (Figure 2) [20]. ular weight of 410.7 g/mol, density of 0.855 g/cm3, melting When the SQ adopts the hexagonal form, it increases temperature of 20°C, and it is soluble in organic solvents the rigidity and the size of the cell membrane. Studies on and insoluble in water [9, 12]. the lipid-protein interaction in cell membranes have Due to its unsaturated− structure, the SQ is sensitive to revealed that the SQ increases the polarity and hydrophobic oxidation; the double bonds pass to the oxidized form by interactions; it is contributing to membrane reconstitution, chain reactions, where the unsaturated carbons join ions functional regulation of proteins, and movement of ions. producing saturated forms of the molecule. Other oxidation erefore, the SQ plays an important role in electrochemical products are generated through self-hydrolytic processes such cell gradient [13, 21]. as peroxides, but the SQ is not susceptible to peroxidation; on Other components such as saponins in interaction with the contrary, it has an antioxidant protective eect by trapping phytosterols and squalene form insoluble complexes, which x oxygen singlets during the reaction processes [4, 13]. the architecture of the lipid bilayer and generate pores that Studies on oxidation of SQ were scarce; until the last participate in the permeability of cell membranes [22, 23]. Only century, the cyclic diperoxides were reported as oxidation 10% of total SQ on the membrane is metabolically active for products. After 80 years, with advanced techniques (1H NMR sterol synthesis, while the rest is stored with triacylglycerides 13 · and C NMR), it was found that oxidation mechanisms and and sterol esters as lipid droplets [21]. · chemical structures of epoxy and alcohol are formed after e SQ store is used to form important molecules such as a prolonged oxidation to 55–150°C [14–17]. β-sitosterol, campesterol, and stigmasterol, which are pre- Naziri et al. [17] studied squalene oxidation at dierent cursors of hormones for the growth (i.e., brassinosteroids) and temperatures and air conditions, nding the formation of plant adaptation to biotic stress [24–26]. e sterols are bio- epoxy with prooxidant activity in the oil at 40°C and 62°C. On synthesized in plant cells via mevalonate or isoprenoids route, the other hand, Psomiadou and Tsimidou [18] reported the where SQ is also metabolized. International Journal of Agronomy 3 Hydrophilic head B C Globular protein Phospholipid bilayer D A Hydrophobic tails Figure 2: Location of minor compounds in the plant cell membrane: oleic acid (A) squalene (B), carotene (C), and tocopherols (D), adapted from Lopez´ et al. [12]. Synthesis of squalene Mammalian cells Prokaryotes MVA pathway MEP pathway Acetyl CoA Pyruvate GA3P Chloroplast Acetoacetyl CoA Tocopherols DXS Mitochondria DXP Ubiquinones HMG-CoA Geranylgeranyl diphosphate Campesterol 2-Methyl-erythritol-4-phosphate Mevalonate Cytosol IDS IPP 24-Methylenelophenol Dimethylallyl-PP IDI Isopentenyl-PP Sesquiterpenes Farnesyl diphosphate GPP FPS 24-Ethylidene-lophenol SQS Farnesyl-PP Squalene Sitosterol HSQS SQS HSQ PSPP Triterpenes Epoxy squalene Cycloartenol Stigmasterol SQS Squalene Figure 3: Routes of squalene biosynthesis via mevalonate (MVA) and via methylerythritol phosphate (MEP).

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