Use of Active Salmon-Lecithin Nanoliposomes to Increase Polyunsaturated Fatty Acid Bioavailability in Cortical Neurons and Mice.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (-50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.

Neurotrophic Effect of Fish-Lecithin Based Nanoliposomes on Cortical Neurons.

Lipids play multiple roles in preserving neuronal function and synaptic plasticity, and polyunsaturated fatty acids (PUFAs) have been of particular interest in optimizing synaptic membrane organization and function. We developed a green-based methodology to prepare nanoliposomes (NL) from lecithin that was extracted from fish head by-products. These NL range between 100-120 nm in diameter, with an n-3/n-6 fatty acid ratio of 8.88. The high content of n-3 PUFA (46.3% of total fatty acid content) and docosahexanoic acid (26%) in these NL represented a means for enrichment of neuronal membranes that are potentially beneficial for neuronal growth and synaptogenesis. To test this, the primary cultures of rat embryo cortical neurons were incubated with NL on day 3 post-culture for 24 h, followed by immunoblots or immunofluorescence to evaluate the NL effects on synaptogenesis, axonal growth, and dendrite formation. The results revealed that NL-treated cells displayed a level of neurite outgrowth and arborization on day 4 that was similar to those of untreated cells on day 5 and 6, suggesting accelerated synapse formation and neuronal development in the presence of NL. We propose that fish-derived NL, by virtue of their n-3 PUFA profile and neurotrophic effects, represent a new innovative bioactive vector for developing preventive or curative treatments for neurodegenerative diseases.

Enzymatic production of bioactive docosahexaenoic acid phenolic ester.

Docosahexaenoic acid (DHA) is increasingly considered for its health benefits. However, its use as functional food ingredient is still limited by its instability. In this work, we developed an efficient and solvent-free bioprocess for the synthesis of a phenolic ester of DHA. A fed-batch process catalyzed by Candida antarctica lipase B was optimised, leading to the production of 440 g/L vanillyl ester (DHA-VE). Structural characterisation of the purified product indicated acylation of the primary OH group of vanillyl alcohol. DHA-VE exhibited a high radical scavenging activity in acellular systems. In vivo experiments showed increased DHA levels in erythrocytes and brain tissues of mice fed DHA-VE-supplemented diet. Moreover, in vitro neuroprotective properties of DHA-VE were demonstrated in rat primary neurons exposed to amyloid-ß oligomers. In conclusion, DHA-VE synergized the main beneficial effects of two common natural biomolecules and therefore appears a promising functional ingredient for food applications.