Multiple Beneficial Health Effects of Natural Alkylglycerols from Shark Liver Oil

Alkylglycerols (alkyl-Gro) are ether lipids abundant in the liver of some elasmobranch fish species such as ratfishes and some sharks. Shark liver oil from Centrophorus squamosus (SLO), or alkyl-Gro mix from this source, have several in vivo biological activities including stimulation of hematopoiesis and immunological defences, sperm quality improvement, or anti-tumor and anti-metastasis activities. Several mechanisms are suggested for these multiple activities, resulting from incorporation of alkyl-Gro into membrane phospholipids, and lipid signaling interactions. Natural alkyl-Gro mix from SLO contains several alkyl-Gro, varying by chain length and unsaturation. Six prominent constituents of natural alkyl-Gro mix, namely 12:0, 14:0, 16:0, 18:0, 16:1 n-7, and 18:1 n-9 alkyl-Gro, were synthesized and tested for anti-tumor and anti-metastatic activities on a model of grafted tumor in mice (3LL cells). 16:1 and 18:1 alkyl-Gro showed strong activity in reducing lung metastasis number, while saturated alkyl-Gro had weaker (16:0) or no (12:0, 14:0, 18:0) effect. Multiple compounds and mechanisms are probably involved in the multiple activities of natural alkyl-Gro.

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The usual composition of alkyl chains in alkyl-Gro from Greenland shark (Centrophorus squamosus) liver oil (SLO) is as follow: 12:0, 1–2%. 14:0, 1–3%; 16:0, 9–13%; 16:1n-7, 11–13%; 18:0, 1–5%; 18:1n-9, 54–68%; 18:1n-7, 4–6%, and minor species (<1%).

Beneficial effects of SLO on health have been recognized in traditional medicine of northern countries involved in fishing, such as Japan, Norway or Iceland. In these countries, the ancestral use of SLO was empirical as strengthening or wound healing medication.  Lipids and phospholipids have prominent roles in cell-to-cell communication and in intracellular signals as well. Many lipid-derived bioactive molecules are agonists of specific membrane receptors: besides prostanoids and leukotriens, recent discoveries of new lipid mediators include docosanoids and many other eicosanoids such as isoprostanes, anandamide, 2-arachidonoylglycerol and other natural lipids acting as cannabinoid receptor agonists. Phospholipidic mediators are as well numerous, ubiquitous and of first rank interest; they include Platelet-activating Factor (PAF), lysophosphatidic acid (Lyso-PA), lysophosphatidylcholine (Lyso-PC), and shingosine-1-P (SP-1P). Several lipids act as intracellular second messengers (diacylglycerols, free fatty acids) or as regulators of transcription factors (free fatty acids, Lyso-PA).

Synthetic short chain alkyl-Gro such as 1-O-pentyl sn glycerol are interesting compounds, which transiently open the blood brain barrier (BBB), allowing increased crossing of the BBB by therapeutic molecules. Parenteral 1-O-decyl-sn-glycerol may also increase carbamazepine crossing through BBB. Oxidation of the natural unsaturated alkyl-Gro on the double bound could lead to short-chain alkyl-Gro with putative similar activities. (Mar Drugs. 2010; 8(7): 2175–2184.)