Eicosapentaenoic acid monoglyceride resolves inflammation in an ex vivo model of human peripheral blood mononuclear cell
Abstract
Phosphorylation and activation of p38 MAPK and NFκB pathways, along with the resulting overproduction of interleukin IL-1β, IL-6, and tumor necrosis factor a (TNFα) is a hallmark of inflammatory disorders. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementations are known to exert anti-inflammatory properties by reduction of keys cytokines and enzymes involved in inflammation. Here, we investigated the anti-inflammatory pathways and mediators modulated by eicosapentaenoic acid monoglyceride (MAG-EPA) on human peripheral blood mononuclear cells (PBMCs) from healthy donors and stimulated, ex vivo, with lipopolysaccharide (LPS). LPS stimulation increased p38 MAPK and NFκB phosphorylation, which was abolished by MAG-EPA treatments. Concomitantly, MAG-EPA also abolished LPS-induced inflammation in PBMCs by reducing IL-1β, IL-6, and TNFα cytokines at protein and transcript levels. Moreover, MAG-EPA decreased the levels of HIF1α in LPS-induced human PBMCs. Results also revealed a decreased of pro-inflammatory enzymes such as Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) in LPS-induced PBMCs. Altogether, the present data suggest that MAG-EPA, represents a new potential therapeutic strategy for resolving inflammation in inflammatory disorders including autoimmune diseases, allergies, asthma, arthritis and cancer.
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Omega-3 PUFAs DHA and EPA have anti-inflammatory properties, and marine-derived omega-3 PUFAs can influence the exercise and nutritional response of skeletal muscle.
“The omega-3 PUFAs (DHA and EPA) are known for their anti-inflammatory properties [32], and marine-derived omega-3 PUFAs can influence the exercise and nutritional response of skeletal muscle [33].”
From Novel Insights on Intake of Fish and Prevention of Sarcopenia: All Reasons for an Adequate Consumption (2020) · cites this paper as [32]
n-3 PUFAs possess anti-inflammatory properties.
“Omega-3 polyunsaturated fatty acids (n-3 PUFAs), which are commonly found in fish oil supplements, are known to possess anti-inflammatory properties”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [41]
Cites
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738 · see citing works
Resolution of inflammation: the beginning programs the end
Serhan, C. N., & Savill, J. (2005) · Nature Immunology · doi:10.1038/ni1276 · Cited by 2,552 · see citing works
Direct transesterification of all classes of lipids in a one-step reaction.
Lepage, G., & ROY, C. C. (1986) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38861-1 · Cited by 2,385 · see citing works
Omega-3 Fatty Acids in Inflammation and Autoimmune Diseases
Simopoulos, A. P. (2002) · Journal of the American College of Nutrition · doi:10.1080/07315724.2002.10719248 · Cited by 2,014 · see citing works
Cytokine Signaling Modules in Inflammatory Responses
O’Shea, J. J., & Murray, P. J. (2008) · Immunity · doi:10.1016/j.immuni.2008.03.002 · Cited by 819 · see citing works
Regulation of hypoxia-inducible factor-1α by NF-κB
van Uden, P., Kenneth, N. S., & Rocha, S. (2008) · Biochemical Journal · doi:10.1042/bj20080476 · Cited by 729 · see citing works
Ziello, J. E., Jovin, I. S., & Huang, Y. (2007) · PubMed Central · Cited by 660 · see citing works
Pharmacology and therapeutics of omega-3 polyunsaturated fatty acids in chronic inflammatory disease
Yates, C. M., Calder, P. C., & Rainger, G. E. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.10.010 · Cited by 396 · see citing works
Bouwens, M., van de Rest, O., Dellschaft, N. S., Bromhaar, M. G., de Groot, C. P. G. M., Geleijnse, J. M., Müller, M. M., & Afman, L. A. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2009.27680 · Cited by 335 · see citing works
Schildberger, A., Roßmanith, E., Eichhorn, T., Straßl, K., & Weber, V. (2013) · Mediators of Inflammation · doi:10.1155/2013/697972 · Cited by 263 · see citing works
de Mello, V. D., Kolehmanien, M., Schwab, U., Pulkkinen, L., & Uusitupa, M. I. J. (2012) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201100685 · Cited by 182 · see citing works
Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration
Tachtsis, B., Camera, D., & Lacham-Kaplan, O. (2018) · Nutrients · doi:10.3390/nu10030309 · Cited by 104 · see citing works
Vedin, I., Cederholm, T., Freund‐Levi, Y., Basun, H., Garlind, A., Irving, G. F., Eriksdotter, M., Wahlund, L., Dahlman, I. A., & Palmblad, J. E. W. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035425 · Cited by 92 · see citing works
Hill, R. J., Dabbagh, K., Phippard, D., Li, C. L., Suttmann, R. T., Welch, M., Papp, E., Song, K. W., Chang, K.-C., Leaffer, D., et al. (2008) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.108.139006 · Cited by 78 · see citing works
Morin, C., Blier, P. U., & Fortin, S. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0653-y · Cited by 67 · see citing works
Docosahexaenoic Acid Derivative Prevents Inflammation and Hyperreactivity in Lung
Morin, C., Fortin, S., Cantin, A. M., & Rousseau, É. (2010) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2010-0156oc · Cited by 50 · see citing works
Inflammation, but not hypoxia, mediated HIF-1α activation depends on COX-2
Stasinopoulos, I. A., O’Brien, D. R., & Bhujwalla, Z. M. (2009) · Cancer Biology & Therapy · doi:10.4161/cbt.8.1.7079 · Cited by 49 · see citing works
Tsunoda, F., Lamon‐Fava, S., Asztalos, B. F., Iyer, L. K., Richardson, K., & Schaefer, E. J. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.05.015 · Cited by 40 · see citing works
Omega-3 Index of Canadian adults.
Langlois, K. A., & Ratnayake, W. M. N. (2015) · PubMed · Cited by 38 · see citing works
IκBβ is a positive and negative regulator of NF-κB activity during inflammation
Kamata, H., Tsuchiya, Y., & Asano, T. (2010) · Cell Research · doi:10.1038/cr.2010.147 · Cited by 35 · see citing works
MAG ‐ EPA resolves lung inflammation in an allergic model of asthma
Morin, C., Fortin, S., Cantin, A. M., & Rousseau, É. (2013) · Clinical & Experimental Allergy · doi:10.1111/cea.12162 · Cited by 34 · see citing works
MAG-EPA reduces severity of DSS-induced colitis in rats
Morin, C., Blier, P. U., & Fortin, S. (2016) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00136.2015 · Cited by 28 · see citing works
Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines
Mozurkewich, E., Berman, D. R., Vahratian, A. M., Clinton, C. M., Romero, V., Chilimigras, J. L., Vázquez, D. M., Qualls, C., & Djurić, Z. (2018) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-018-1899-6 · Cited by 26 · see citing works
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Cited by
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Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death
Sun, Q., Zhou, H., & Mao, X. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/2749173 · Cited by 157 · see citing works
Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration
Tachtsis, B., Camera, D., & Lacham-Kaplan, O. (2018) · Nutrients · doi:10.3390/nu10030309 · Cited by 104 · see citing works
Yaghmur, A., Al-Hosayni, S., Amenitsch, H. W., & Salentinig, S. (2017) · Langmuir · doi:10.1021/acs.langmuir.7b03078 · Cited by 65 · see citing works
Rondanelli, M., Rigon, C., Perna, S., Gasparri, C., Iannello, G., Akber, R., Alalwan, T. A., & Freije, A. M. (2020) · Nutrients · doi:10.3390/nu12020307 · Cited by 44 · see citing works
Gao, K., Chu, W., Sun, J., & Mao, X. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.127225 · Cited by 44 · see citing works
Cauble, R. N., Greene, E. S., Orlowski, S., Walk, C. L., Bedford, M. R., APPLE, J. K., Kidd, M. T., & Dridi, S. (2020) · Poultry Science · doi:10.1016/j.psj.2020.05.005 · Cited by 28 · see citing works
Effect of prenatal EPA and DHA on maternal and umbilical cord blood cytokines
Mozurkewich, E., Berman, D. R., Vahratian, A. M., Clinton, C. M., Romero, V., Chilimigras, J. L., Vázquez, D. M., Qualls, C., & Djurić, Z. (2018) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-018-1899-6 · Cited by 26 · see citing works
Lower Serum n-3 Fatty Acid Level in Older Adults with Sarcopenia
Jang, I., Jung, H., Park, J. H., Kim, J. H., Lee, S., Lee, E., Lee, J. Y., Park, S. J., Kim, D. A., Kim, S. J., et al. (2020) · Nutrients · doi:10.3390/nu12102959 · Cited by 25 · see citing works
Omega-3 fatty acid nanocarriers: Characterization and potential applications
Yaghmur, A., Ghayas, S., Jan, H., Kalaycıoğlu, G. D., & Moghimi, S. M. (2023) · Current Opinion in Colloid & Interface Science · doi:10.1016/j.cocis.2023.101728 · Cited by 22 · see citing works
Nanoencapsulation of food ingredients by cubosomes and hexosomes
Yaghmur, A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815673-5.00012-x · Cited by 14 · see citing works
Gao, K., Huang, W., Dong, H., Sun, J., Jiang, H., & Mao, X. (2024) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.4c00368 · Cited by 11 · see citing works
Hajri, T., Ewing, D. R., Talishinskiy, T., Amianda, E. A., Eid, S. R., & Schmidt, H. J. (2021) · Journal of Nutrition · doi:10.1093/jn/nxab167 · Cited by 4 · see citing works
Efek Suplementasi Omega 3 dan Latihan Fisik Terhadap Respon Inflamasi
Ayubi, N., Purwanto, B., & Rejeki, P. S. (2020) · JOSSAE (Journal of Sport Science and Education) · doi:10.26740/jossae.v5n2.p116-123 · Cited by 3 · see citing works
Kowara, M., Kasarełło, K., Czarzasta, K., Opolski, G., & Cudnoch‐Jędrzejewska, A. (2018) · Medical Hypotheses · doi:10.1016/j.mehy.2018.10.026 · Cited by 3 · see citing works
Gao, K., Yao, X. H., Liu, J., Hu, Y., Jiang, H., Sun, J., Dong, H., & Mao, X. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.5c10334 · Cited by 2 · see citing works
Calorie‐Reduced Lipids and Health
Shahidi, F., & Nguyen, L. V. (2020) · Wiley eBooks · doi:10.1002/047167849x.bio111 · Cited by 1 · see citing works
- Authors
- Morin, C., Charbonneau, L., Ouellet, N., Ouellet, H., Blier, P. U., Dufresne, F., & Fortin, S.
- Affiliations
- Université du Québec à Rimouski (CA)
- Corresponding author
- Fortin, Samuel
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2017-07
- Volume
- 807
- Pages
- 205-211
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W2613043864
- Cited by
- 16
- References
- 26
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 1
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Physical Sciences › Chemistry › Organic Chemistry › Edible Oils Quality and Analysis
- Keywords
- omega-3 polyunsaturated fatty acids, anti-inflammatory activity, peripheral blood mononuclear cells, lipopolysaccharide-induced inflammation, p38 MAPK, NF-κB signaling, inflammatory cytokines, IL-1β, interleukin-6, TNF-α, HIF-1α, cyclooxygenase-2, 5-lipoxygenase
- MeSH terms
- Adult, Arachidonate 15-Lipoxygenase, Arachidonate 5-Lipoxygenase, Enzyme Activation, Humans, Inflammation, Leukocytes, Mononuclear, Mitogens, RNA, Messenger, Biomarkers, Gene Expression Regulation, Enzymologic, Cytokines, MAP Kinase Signaling System, Cell Proliferation, Monoglycerides, Hypoxia-Inducible Factor 1, alpha Subunit, Young Adult
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