Shark Liver Oil Research Articles

Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study

Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle. We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n=10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n=4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n=10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years). In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21-0.43), 0.39 (95% CI 0.25-0.61) and 0.42 (95% CI 0.30-0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR=0.66; 95% CI 0.56-0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score. The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings. National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).

Stability of shark (Centrophorus sp.) liver oil rich in squalene as an immunostimulant

Shark liver oil has been widely produced in Indonesia; however, many shark liver oil products still do not meet the established standards. This research involves the addition of antioxidants to stabilize the oil as an effort to extend its shelf life. The objectives of this study were to determine the immunostimulant activity, assessed the synergistic effect of vitamin E in shark liver oil rich in squalene, and identified the optimum concentration of the antioxidant vitamin E in maintaining its stability. Immunostimulant activity was tested by observing spleenocyte proliferation, phagocytic index, and capacity in the peritoneal cavity cells of mice. The stability of the oil was examined by an accelerated method using an oven, what was called the schaal oven test at 40 °C. The research results indicate that shark liver oil possesses immunostimulant effects; however, with an increasing dosage of fish oil, there is no significant improvement. The presence of vitamin E in cod liver oil exhibited a synergistic effect on spleenocyte proliferation for all dosages, while the phagocytic index and capacity at a dosage of 100 μg/mL showed synergy. However, at a dosage of 50 μg/mL, the phagocytic index and capacity did not exhibit synergy with the immunostimulant. The optimal concentration of the antioxidant vitamin E in maintaining oil stability was found to be 100 ppm.

Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of Polyunsaturated C18:3 Omega-3 and Omega-6 MEL Triene Derivatives.

The asymmetric synthesis of polyunsaturated triene C18:3 n-3 and C18:3 n-6 methoxylated ether lipids (MEL) of the 1-O-alkyl-sn-glycerol type is described as possible structural candidates for a triene C18:3 MEL of an unknown identity found in a mixture of shark and dogfish liver oil. Their C18:3 hydrocarbon chains constitute an all-cis methylene skipped n-3 or n-6 triene framework, along with a methoxyl group at the 2'-position and R-configuration of the resulting stereogenic center. The methoxylated polyenes are attached by an ether linkage to the pro-S hydroxymethyl group of the glycerol backbone. The syntheses were based on the polyacetylene approach that involves a semi-hydrogenation of the resulting triynes. Both syntheses were started from our previously described enantio- and diastereomerically pure isopropylidene-protected glyceryl glycidyl ether, a double-C3 building block that was designed as a head group synthon for the synthesis of various types of MELs.

Squalene Biosynthesis in Engineered Escherichia Coli

AbstractSqualene is a natural triterpenoid that is important in medicine, and daily-use chemical and nutraceutical industries. The demand for squalene remains high and constant. Shark liver oil is the source of the compound; however, the source is unsustainable due to the protection of the gradually extinct animal. This study aimed to construct an engineered Escherichia coli strain to produce squalene in a green and sustainable manner. In this study, the activity of several squalene synthases from different species was screened. Gas chromatography-mass spectrometry and high-performance liquid chromatography were used for chemical structure identification. The mevalonate pathway (MVA) was constructed into BL21(DE3) to enhance the supply of farnesyl diphosphate to obtain squalene at a concentration of 69.3 mg/L. IspH was overexpressed in BL21(DE3) to decrease squalene production due to the accumulation of dimethylallyl diphosphate. By balancing the overexpression of ispH and ispG, the production of squalene increased to 298.3 mg/L. The genes of the MVA pathway were further separated upstream and downstream, and constructed into two plasmids with different origins to balance the metabolic flux. By optimizing the expression strength of genes in MVA and 2-C-methyl-d-erythritol-4-phosphate pathway, an engineered strain was finally obtained with squalene production of 974.3 mg/L. By replacing chassis cell BL21(DE3) with XL1-Blue, squalene production was further increased to 1,274 mg/L.

Kilo-Scale GMP Synthesis of Renewable Semisynthetic Vaccine-Grade Squalene.

Emulsions of the triterpene squalene ((6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of trans-β-farnesene ((6E)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process. The scalability of the proposed route was verified by a kilo-scale GMP synthesis. We also report data demonstrating the synthesized semi-synthetic squalene's physical stability and biological activity when used in a vaccine adjuvant formulation.

Enhancement of Icariin Aphrodisiac Effect by Solid-SNEDDS Method Using Shark Liver Oil Phase

The Epimedium brevicornu Maxim plant contains icariin, a flavonoid compound known for its aphrodisiac effects. However, icariin has low solubility and bioavailability. This study aims to find the best formula for S-SNEDDS icariin, its physical properties, characteristics, and aphrodisiac activity. Using the S-SNEDDS (Solid-Self Nanoemulsifying Drug Delivery System) method with shark liver oil phase is expected to increase the solubility and bioavailability of icariin. The optimum formula used is tween 80 (72.5%): PEG 400 (13.75%) and shark liver oil (13.75%). The optimal formula of S-SNEDDS icariin with the adsorption method to solid carriers requires aerosol 200 as much as 783±28.86mg per 1mL. S-SNEDDS icariin has characteristics with an average emulsification time of 12.88±0.26 seconds, transmittance value of 98.08±0.94%, droplet size 171.8±8.9 nm, zeta potential -35.2±1.1 mV, flow speed less than 10 seconds, resting angle 35.159°. The dissolution test of S-SNEDDS icariin is better than icariin instead of S-SNEDDS. S-SNEDDS icariin dose 50 mg/KgBW has a better aphrodisiac effect than pure icariin 100 mg/kgBW.

Plant-derived squalene supplementation improves growth performance and alleviates acute oxidative stress-induced growth retardation and intestinal damage in piglets

Piglets are particularly susceptible to oxidative stress, which causes inferior growth performance and intestinal damage. Squalene (SQ), a natural bioactive substance enriched in shark liver oil, shows excellent antioxidant properties and can currently be obtained at a low cost from deodorizer distillate during the production of plant oil. This study aimed to evaluate the effects of plant-derived SQ supplementation on the growth performance of piglets and explore the beneficial roles of SQ against oxidative stress and intestinal injury in diquat-challenged piglets. Forty piglets were randomly divided into five groups and fed a basal diet supplemented with SQ at 0, 500, 1000, or 2000 mg/kg for 5 weeks. Acute oxidative stress was induced in the piglets with diquat (10 mg/kg BW) at the fourth week of the experiment, followed by a 7-d recovery period. Results showed that before the diquat challenge, SQ supplementation significantly improved growth performance (average daily gain and feed conversion ratio) and serum antioxidant status, and after the diquat challenge, SQ supplementation significantly mitigated diquat-induced growth arrest, intestinal villous atrophy, intestinal epithelial cell apoptosis, intestinal hyperpermeability, and deficiency of intestinal epithelial tight junction proteins (zonula occludens-1, occludin, and claudin-3). Under oxidative stress induced by diquat, SQ supplementation consistently improved the antioxidant status of the small intestine, liver, and muscle. In vitro, SQ was shown to alleviate hydrogen peroxide (H2O2)-induced increase of the levels of intracellular reactive oxygen species and apoptosis of porcine intestinal epithelial cells. Taken together, SQ supplementation improves growth performance and effectively alleviates acute oxidative stress-induced growth retardation and intestinal injury via improving antioxidant capacity in piglets. Our findings may provide an efficient strategy for alleviating oxidative stress-induced inferior growth performance and intestinal damage in piglets.

Facile Synthetical Method of Squalene from Vegetable Residue

The proscription of the use of shark liver oil for the production of squalene by the International Ocean Conservation and Advocacy Organization (IOCAO) for the protection of sharks in 2005, leads to a great reduction in its quantity in circulation. The quantity in circulation is not enough to meet its growing demand. Therefore, the research for the synthesis of squalene was extended to the use of Gmelina arborea leaves. This was carried out by treating the dry leaves of Gmelina arborea with methanol and a barium chloride catalyst at 90 °C at varying reaction times in minutes. The products were analyzed using gas chromatography and mass spectrometry (GC-MS). The GC-MS revealed the following results; 162.39, 171.98, 145.69, 92.43, 108.32 and 118.83 mg/g for the reaction times of 10, 20, 30, 40, 50 and 60 minutes, respectively. The maximum yield achieved was 171.98 mg/g at a reaction time of 20 minutes and the minimum yield was 92.43 mg/g at a time of 40 minutes. This method is fast, safe, cost-efficient and economically viable for squalene production. Hence, Gmelina arborea has the potential for squalene production to meet up with the global demand.

Fatty Acid Profile and Squalene Content in Cucumber Seed Oil (Cucumis sativus)

Cucurbitaceae is known as a source of vegetable oil that can be used in the fields of food, medicine, and cosmetics. Several studies showed that vegetable oil from the Cucurbitaceae contains squalene. Squalene is a high-economic value compound that was originally found in shark liver oil. This compound is proven to be very beneficial for health and cosmetics. The objectives of the study are to determine the fatty acid profile and squalene content of cucumber seed oil using the Gas Chromatography-Mass Spectrometry (GC-MS) method. Starting with the preparation of cucumber seeds by drying the clean seed in an oven at 60 0C for 1 hour, then the seeds were extracted using 2 methods namely maceration and a continuous extraction method with a soxhlet extractor. The yield of crude oil obtained by the soxhlet extractor is higher than maceration, which was 19.38 ± 0.94%, yellow colour, and distinct aroma, 2% water oil content; oil density of 0.96 g/mL; free fatty acid levels of 3.51%; an acid value of 4.97 mg NaOH/g oil; and peroxide value of 0.82 meq O2/g oil. The results of the GC-MS analysis showed that cucumber oil was composed of 3 main components namely palmitic acid, linoleic acid, and squalene.
 Keywords: Cucumber seed oil, Cucumis sativus, fatty acids, squalene.

ISOLASI JENIS ASAM LEMAK DARI BERBAGAI BAHAN BAKU : ARTIKEL REVIEW

Fats or triglycerides are compounds derived from glycerin with three fatty acids, which in the intestine are hydrolyzed into their components. Fatty acids can be obtained from various sources, both animal and vegetable. Fatty acids derived from animal fats are unsaturated fatty acids contained in fish oil. Fatty acids derived from several types of vegetable oils, such as palm oil and cocoa butter, contain saturated fatty acids consisting of palmitic acid (C16H31COOH) and stearic acid (C17H35COOH). Obtaining fatty acids can be conducted by the isolation method, so that the type of fatty acids contained in a sample can be determined, the purpose of this study is to determine the types of fatty acids isolated from various sources of raw materials using the literature review study method. The results of various studies show that fatty acids can be obtained from various natural materials such as animal and vegetable products, including oil palm skin, shark liver oil, catfish oil, wet and dry Moringa seeds, nutmeg seed oil, melinjo fruit seeds, marine yeast oleaginous, olive oil, and fusarium verticilloides species. The types of fatty acids obtained were oleic acid, palmitic fatty acid, DHA, omega 3 and omega 6, trimyristin fatty acid, isanic acid, linoleic acid, stearic acid, palmitoleic acid. So that by isolating the sample, it can be known the type of fatty acids contained in it, both from animals and plants.

Pid-Based Bottle Shark Heart Heater Design and Development

Traditional medicines are ingredients or ingredients in the form of plant ingredients, animal ingredients, mineral ingredients, galenic preparations, or mixtures of these materials, which have been used for generations for treatment and can be applied according to the norms in force in society. Bottle shark (Centrophorus atromarginatus) has good prospects as a producer of liver oil; this fish is easy to catch and occurs in relatively large quantities in Indonesian waters. The catch rate until now is only 39% of its sustainable potential. Bottled shark liver oil contains 90% squalene, Vitamin A, and Omega, which are very useful for the human body as a supplement for heart disease and stomach ulcers and increase stamina and brain intelligence. The rapid Development of technology certainly benefits the people who use it. One example of today's use of technology is applying a technology system for the fisheries sector. This tool works automatically to monitor the processing of bottled shark livers. That way, fishermen don't have to worry about cloudy weather or things that will take longer than processing the shark liver bottle. This Bottle Shark Liver Heater uses temperatures at 31˚, 32˚, 33˚, 34˚, and 35˚. With PID (Proportional Integral Derivative) control, the quality of the Bottle Shark liver can be maintained. This tool is supported by a DS18B20 temperature sensor, Arduino uno, Relay, Ceramic Heater element, DC Fan, LCD 16X12, Power Supply, and Switch. It is hoped that the community, with this automatic system device, can make it easier to manage Bottle Shark Liver Oil.

Semi-synthetic terpenoids with differential adjuvant properties as sustainable replacements for shark squalene in vaccine emulsions

Synthetic biology has allowed for the industrial production of supply-limited sesquiterpenoids such as the antimalarial drug artemisinin and β-farnesene. One of the only unmodified animal products used in medicine is squalene, a triterpenoid derived from shark liver oil, which when formulated into an emulsion is used as a vaccine adjuvant to enhance immune responses in licensed vaccines. However, overfishing is depleting deep-sea shark populations, leading to potential supply problems for squalene. We chemically generated over 20 squalene analogues from fermentation-derived β-farnesene and evaluated adjuvant activity of the emulsified compounds compared to shark squalene emulsion. By employing a desirability function approach that incorporated multiple immune readouts, we identified analogues with enhanced, equivalent, or decreased adjuvant activity compared to shark squalene emulsion. Availability of a library of structurally related analogues allowed elucidation of structure-function relationships. Thus, combining industrial synthetic biology with chemistry and immunology enabled generation of sustainable terpenoid-based vaccine adjuvants comparable to current shark squalene-based adjuvants while illuminating structural properties important for adjuvant activity.

Asymmetric synthesis of methoxylated ether lipids: Total synthesis of two monounsaturated C18:1 and a saturated C18:0 methoxylated ether lipid derivatives

The report describes the first asymmetric synthesis of three derivatives of methoxylated ether lipids (MELs) of the 1-O-alkyl-sn-glycerol type present in the liver oil of various species of cartilaginous fish, all three possessing eighteen-carbon hydrocarbon chains in their ether entity. Two of them were already known, the saturated C18:0 and the monounsaturated C18:1 n-14 MELs, whereas the third one is a novel monounsaturated C18:1 n-9 MEL. All three were isolated and detected by LC-MS studies of a MEL sample obtained from dogfish and shark liver oil. The structural identity of the novel one was unequivocally confirmed to be the C18:1 n-9 MEL by its total synthesis after comparison based on their MS/MS spectra. Their synthesis made use of our previously described enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, a double-C3 building block serving as a head group synthon in synthesis of various types of MELs. They were all obtained in high chemical and stereochemical purity and good overall yields.

Mercury Exposure from the Consumption of Dietary Supplements Containing Vegetable, Cod Liver, and Shark Liver Oils.

Vegetable and fish oils constitute a significant part of all dietary supplements. Due to increasing environmental pollution, the raw materials used for their production may be contaminated with toxic substances, including metals. The aim of the present study was to determine the mercury (Hg) content in vegetable oils, shark liver oils, and cod liver oils. The tests conducted were to help determine the level of mercury contamination of the tested preparations and the related potential threat to human health. The amount of Hg in the tested dietary supplements was compared, and the amount of the metal consumed at various times of use was determined. A total of 36 preparations of dietary supplements available on the Polish market were used for the study. The method of atomic absorption spectrometry using the amalgamation technique was used for the determinations (AMA 254, Altec, Czech Republic). Among the sample of all of the tested preparations, the Hg concentration ranged from 0.023 to 0.427 µg/kg, with an average of 0.165 µg/kg. Differences in Hg content in the various tested preparations (shark liver oil, cod liver oil, and vegetable oils) were statistically significant. The average concentration of Hg in the vegetable oils (0.218 µg/kg) was more than twice that of the cod liver oils (0.106 µg/kg) and shark liver oils (0.065 µg/kg). In none of the tested preparations did the amount of Hg exceed the acceptable standard for dietary supplements (0.10 mg/kg). The analysis showed that the Hg content in vegetable oils, shark liver oils, and fish oils from the Polish market is at a low level, guaranteeing the safety of their use, and as such, they do not pose a threat to health.

Shark liver and flaxseed oils as alternatives to soybean oil in the lipid quality of Japanese quail eggs

PurposeThe objective of this study was to assess the incorporation of polyunsaturated omega 3 and omega 6 fatty acids in the eggs of Japanese quails (Coturnix coturnix japonica) fed with soybean, flaxseed and shark liver oils, as well as to assess their effects on the chemical composition and lipid quality of the yolks.Design/methodology/approachThe total of 252 units of quails were distributed in a completely randomized design with seven treatments and six replications, totaling 42 experimental design units. The sources of oils and their inclusions in the experimental diet were 2% of soybean oil (S), 2% of flaxseed oil (L) and 2% shark liver oil (T), obtained from the species Carcharhinus acronotus, and the mixtures of 1% S + 1% L (SL); 1% S + 1% T (ST); 1% L + 1% T (LT) and 0.67% S + 0.67% L + 0.67% T (SLT).FindingsThe proximate composition of the egg yolk was not changed to the supplementation of lipid sources added in quail diet. The total replacement of soybean oil by shark liver oil reduced the cholesterol content in the yolk by 19% (T = 282.97 mg cholesterol/100 g egg) and the addition of flaxseed oil produced eggs with greater amount of polyunsaturated fatty acids (PUFAs) (LS = 18.32%). The treatments with flaxseed oil and its mixtures (soybean oil + flaxseed oil and flaxseed oil + shark liver oil) effectively contributed to reducing the ω-6:ω-3 ratio and enriching the quail eggs with PUFAs, especially linolenic acid (18: 3n3c) and EPA (20: 5n3c).Originality/valueThus, manipulation in the diet of quails enriched the content of essential PUFAs and reduced the cholesterol content in the yolk. The flaxseed oil was the lipid source that influenced to improve the quality of the egg yolk. These results have practical applicability for the quail egg industry.

Challenges in avoiding deep-water shark bycatch in Azorean hook-and-line fisheries

AbstractDeep-water sharks are highly diverse, vulnerable, and understudied as a group, despite the increasing pressures on their populations. Twenty-five species of deep-water sharks have been recorded in the Azores, an oceanic archipelago in the mid-North Atlantic, that are regularly caught as bycatch in hook-and-line fisheries. Avoiding the bycatch of deep-water sharks presents multiple challenges due to their high catchability, difficulties in correctly identifying species, and the general lack of data on these species. This review summarizes the findings of recent studies from the region, providing an up-to-date science-based framework for mitigating bycatch effects of Azorean hook-and-line fisheries. Several depth-based, area-based, and gear-based measures have been studied that demonstrate the potential to either avoid or increase the survival of deep-water shark bycatch. However, these measures may have limited efficacy for some species (e.g. highly mobile species) and thus, limited widespread applicability. Convincing fishers to avoid deep-water shark bycatch is also a challenge given the antagonistic interactions with sharks damaging the catch and fishing gear, while simultaneously a market incentive for shark liver oil remains. It highlights the need to proactively engage fishers and incentivize the mitigation of bycatch of deep-water sharks in Azorean waters.

MICROALGAE - MACROALGAE BASED NUTRACEUTICALS AND THEIR BENEFITS

Algae produce some substances that have a positive effect on human health. Algae are known as sources suitable for use in food and foods with the bioactive components they produce at a high rate. These ingredients are called nutraceuticals. Nutraceuticals are products that have physiological benefits and are protective against chronic diseases and are generally recommended to be used as medicines. Bioactive nutraceuticals from aquaculture; fish oil (ω-3), seal blubber oil, algae oil, shark liver oil, shark cartilage, chitin, chitosan as well as enzymes, peptides and their components, vitamins (vitamin A,D,E, β carotene), macroalgae and its components, protein hydrolysates and other products. It is known that these high-value components in algae regulate immunity, prevent diabetes, oxidation, inflammation, high cholesterol and cardiovascular diseases, and have positive effects against obesity and unbalanced nutrition. In this review, information is given about micro and macroalgae-based nutraceuticals, their application areas and potential health benefits.

Using Compound-Specific Carbon Stable Isotope Analysis of Squalene to Establish Provenance and Ensure Sustainability for the Deep-Water Shark Liver Oil Industry

Deep-water dogfish (sharks) are caught on Australia’s continental shelf as by-products to other deep-water species with revenue derived from fillets for human consumption and from the livers which are sold for their oil content. Deep-water dogfish utilise a large oil-rich liver for buoyancy, which may account for 20–25% of their body weight. An important constituent of certain dogfish liver oil is squalene, a highly unsaturated triterpenoid (C30H50) hydrocarbon which in some species can be up to 90% of the oil, though in the Australian commercial species it is typically around 50%. Squalene (and deep-water dogfish liver oil in general) has a long-standing high value in products, such as cosmetics and nutraceuticals. Manufacturers are increasingly required to demonstrate the sustainability of products, and this is integral to the importance of demonstrating product provenance. Australia’s mid-slope deep-water dogfish fishery is recognised globally as well managed and sustainable; therefore, it is important to be able to distinguish products derived from these regions from other unregulated, unsustainable and cheaper sources in order to protect Australia’s competitive advantages and ensure sustainability. In this study, we have sourced deep-water dogfish liver oil samples originating from Southeast Australia, New Zealand, India, Northeast Africa and the Arabian Sea. The squalene was isolated by commercial or laboratory processing. A compound-specific carbon stable isotope analysis of the derived squalene was then used to determine isotopic resolution and assign the likely origins of a variety of commonly available off-the-shelf nutraceuticals in Australian outlets. Squalene sourced and produced from Southeast Australian and New Zealand dogfish liver oils showed δ13C values in the range of −22.1 to −24.2‰, with all other squalene samples distinguishable at −19.9 to −20.7‰. Many of the off-the-shelf squalene products claiming to be of Australian origin showed δ13C values very distinct from the range of the genuine Southeast Australian- and New Zealand-produced squalene.

Anti-Angiogenic and Cytotoxicity Effects of Selachyl Alcohol Analogues

The active ingredients in the shark liver oil (SLO) mixture were found to be a group of etherlinked glycerol known as alkylglycerols (AKGs). During the last century, initial clinical use of the SLO mixture was for treating leukemias and later preventing radiation sickness from cancer x-ray therapy. Selachyl alcohol is one of the most abundant AKGs in the SLO mixture and it displayed strong activity in reducing lung metastasis number on a model of grafted tumor in mice (Lewis lung carcinoma cells). In this study, selachyl alcohol analogue containing methoxyl (7), gem-difluorinated (8), azide (9) and hydroxyl (10) group at the 12 position in the alkyl chain were synthesized and compared regarding their cytotoxicity and anti-migratory effects on Human Umbilical Vein Endothelial Cell line. AKGs 7-10 were synthesized according to the literature procedure. The cytotoxicity of the studied AKGs was evaluated by the MTT test and Human Umbilical Vein Endothelial Cell line (HUVEC) was used as an in vitro model to evaluate their anti-migratory effects. The four AKGs have substantially the same toxicity threshold (≥ 12 μM), whereas they have an anti-migratory activity significantly different on endothelial cells. AKGs 9 and 10 significantly reduce the chemotactic migration induced by VEGF, but analogue (10) containing the hydroxyl group at the 12 position in the alkyl chain was the most potent anti-VEGF inhibitor. We presented here a series of four synthetic selachyl alcohol analogues, among which AKGs 9 and 10 showed the ability to inhibit endothelial cell migration. The relationship structures and anti-VEGF effects of these analogues were also evaluated and discussed. Unnatural synthesized AKGs could be explored as one new source of anticancer agents.

Development of a High-Performance Thin-Layer Chromatography Method for the Quantification of Alkyl Glycerolipids and Alkenyl Glycerolipids from Shark and Chimera Oils and Tissues

Ether lipids are composed of alkyl lipids with an ether bond at the sn-1 position of a glycerol backbone and alkenyl lipids, which possess a vinyl ether bond at the sn-1 position of the glycerol. These ether glycerolipids are present either as polar glycerophospholipids or neutral glycerolipids. Before studying the biological role of molecular species of ether glycerolipids, there is a need to separate and quantify total alkyl and alkenyl glycerolipids from biological samples in order to determine any variation depending on tissue or physiopathological conditions. Here, we detail the development of the first high-performance thin-layer chromatography method for the quantification of total alkyl and alkenyl glycerolipids thanks to the separation of their corresponding alkyl and alkenyl glycerols. This method starts with a reduction of all lipids after extraction, resulting in the reduction of neutral and polar ether glycerolipids into alkyl and alkenyl glycerols, followed by an appropriate purification and, finally, the linearly ascending development of alkyl and alkenyl glycerols on high-performance thin-layer chromatography plates, staining, carbonization and densitometric analysis. Calibration curves were obtained with commercial alkyl and alkenyl glycerol standards, enabling the quantification of alkyl and alkenyl glycerols in samples and thus directly obtaining the quantity of alkyl and alkenyl lipids present in the samples. Interestingly, we found a differential quantity of these lipids in shark liver oil compared to chimera. We quantified alkyl and alkenyl glycerolipids in periprostatic adipose tissues from human prostate cancer and showed the feasibility of this method in other biological matrices (muscle, tumor).