The effects of liposomes containing astaxanthin ethers on cytokine secretion by human peripheral blood mononuclear cells


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Relevance. According to the literature, astaxanthin (AST) esters have a pronounced neuroprotective and anti-inflammatory effect in experimental animals with neurodegeneration. Due to the low water solubility, the use of AST esters in the form of phospholipid nanoemulsions is promising. The principal mechanisms of the neuroprotective effect of AST esters include anti-inflammatory action, so it is relevant to study the anti-inflammatory and immunomodulatory effect of nanoemulsions containing AST esters. The aim of this work was to study the effect of phospholipid-based nanoemulsions of AST esters on the secretion of major cytokines and inflammatory mediators (GM-CSF (granulocyte-macrophage colony-stimulating factor), IL-ip, IL-6, IFNy) by human peripheral blood mononuclear cells (PBMC). Material and Methods. Lipid nanoemulsions were prepared from Lipoid S75 by hot emulsification method. AST esters from Haematococcus pluvalis were used for incorporation into nanoemulsions. PBMCs from 6 healthy volunteers (men, age 21-31 years) were isolated from blood in a one-step ficoll urographin density gradient. Cultivation was performed under the following conditions: 1) without addition of nanoemulsions and phytohemagglutinin A (PGA); 2) with PGA, without nanoemulsions; 3) with PGA and nanoemulsions of AST esters; 4) with PGA and nanoemulsions containing no AST esters; 5) with nanoemulsions of AST esters; 6) with nanoemulsions containing no AST esters. Multiplex analysis was used to determine cytokines in the cell supernatants. Results. Nanoemulsions with AST esters suppressed the FGA-stimulated secretion of innate and adaptive immunity cytokines (GM-CSF, IL-1P, IL-6, IFNy) by PBMCs. Addition of nanoemulsions without AST to the PBMCs partially suppressed cell activation by inhibiting the secretion of adaptive immunity cytokine IFNy, but did not affect the levels of proinflammatory cytokines. Conclusion. The results indicate an anti-inflammatory and immunomodulatory effect of AST esters in the form of nanoemulsions, which shows the prospects for further studies of their effects mediating neuroprotection in models of neurodegenerative diseases.

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作者简介

I. Malashenkova

Kurchatov Institute; Federal State Budget Institution of Science State Research Center of The Russian Federation Institute of Medical and Biological Problems Russian Academy of Sciences

Email: malashenkova.irina@bk.ru
Ph.D. (Med.)

S. Krynskiy

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Ph.D. (Med.)

D. Ogurtsov

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Ph.D. (Med.)

A. Ratushnyy

Federal State Budget Institution of Science State Research Center of the Russian Federation Institute of Medical and Biological Problems Russian Academy of Sciences

Email: malashenkova.irina@bk.ru

Ph.D. (Biol.)

N. Lotosh

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Ph.D. (Chem.)

E. Kulikov

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Junior Research Scientist

A. Akulova

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Research Technician

S. Moskvina

Kurchatov Institute

Email: malashenkova.irina@bk.ru

Ph.D. (Biol.)

A. Selishcheva

Kurchatov Institute; Lomonosov Moscow State University

Email: malashenkova.irina@bk.ru

Dr.Sc. (Chem.)

N. Didkovsky

Federal State Budget Institution of Science State Research Center of The Russian Federation Institute of Medical and Biological Problems Russian Academy of Sciences

编辑信件的主要联系方式.
Email: malashenkova.irina@bk.ru

Dr.Sc. (Med.)

参考

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  7. Wang C.C., Shi H.H., Xu J., et al. Docosahexaenoic acid-acylated astaxanthin ester exhibits superior performance over non-esterified astaxanthin in preventing behavioral deficits coupled with apoptosis in MPTP-induced mice with Parkinson’s disease. Food Funct. 2020; 11: 8038-8050.
  8. Kulikova I.S., Lotosh N.Yu., Turanova V.A., et al. Stabilized nanoemulsions of astaxanthin esters of known fatty-acid composition. Pharmaceutical Chemistry Journal. 2020; 54(8): 811-815.
  9. Lotosh N.Yu., Kryuchkova A. V., Kulikov E.A., et al. Effect of Nanoemulsions Containing Astaxanthin or Its Esters on the Spatial Behavior of 5XFAD Mice. Nanobiotechnology Reports. 2022; 17: 227-234.
  10. Chen S.S., Keenan R.M. Effect of phosphatidylcholine liposomes on the mitogen-stimulated lymphocyte activation. Biochem. Biophys. Res. Commun. 1977; 79(3): 852-858.

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2. Secretion of cytokines GM-CSF (a), IL-1β (b), IL-6 (c), IFNγ (d) MNCs under incubation conditions after 24 h. From left to right: spontaneous secretion, secretion upon addition of PHA, secretion upon addition of PHA and S75 nanoemulsions with AST esters, secretion with the addition of PHA and S75 nanoemulsions; * - significant (p < 0.05) differences with the base level of secretion

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