N-Eicosapentaenoyl Dopamine, A Conjugate of Dopamine and Eicosapentaenoic Acid (EPA), Exerts Anti-inflammatory Properties in Mouse and Human Macrophages.

Abstract

A large body of evidence suggests that dietary n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), contribute to a reduced inflammatory tone thereby lowering the risk for several chronic and degenerative diseases. Different mechanisms have been proposed to explain these anti-inflammatory effects, including those involving endocannabinoids and endocannabinoid-like molecules. In this context, fatty acid amides (FAAs), conjugates of fatty acids with amines or amino acids, are an emerging class of compounds. Dopamine conjugates of DHA (N-docosahexaenoyl dopamine, DHDA) and EPA (N-eicosapentaenoyl dopamine, EPDA) have previously been shown to induce autophagy, apoptosis, and cell death in different tumor lines. Additionally, DHDA has displayed anti-inflammatory properties in vitro. Here, we tested the immune-modulatory properties of EPDA in mouse RAW 264.7 and human THP-1 macrophages stimulated with lipopolysaccharide (LPS). EPDA suppressed the production of monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6) in both cell lines, and nitric oxide (NO), and macrophage-inflammatory protein-3α (MIP3A) in RAW 264.7 macrophages. At a transcriptional level, EPDA attenuated cyclooxygenase-2 (COX-2) expression in both cell lines and that of MCP-1, IL-6, and interleukin-1β (IL-1β) in THP-1 macrophages. Although further research is needed to reveal whether EPDA is an endogenous metabolite, our data suggest that this EPA-derived conjugate possesses interesting immune-modulating properties.

• Authors: Giuseppina Augimeri, Pierluigi Plastina, Giulia Gionfriddo, Daniela Rovito, Cinzia Giordano, Alessia Fazio, Ines Barone, Stefania Catalano, Sebastiano Andò, Daniela Bonofiglio, Jocelijn Meijerink, Renger Witkamp
• Journal: Nutrients (Nutrients) Vol. 11 Issue 9 (Sep 18 2019) ISSN: 2072-6643 [Electronic] Switzerland
• PMID: 31540502 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Fatty Acids, Unsaturated
• Eicosapentaenoic Acid
• Cyclooxygenase 2
• Dopamine

Topics

• Animals
• Anti-Inflammatory Agents (chemistry, pharmacology)
• Cells, Cultured
• Cyclooxygenase 2 (metabolism)
• Cytokines (metabolism)
• Dopamine (chemistry, pharmacology)
• Eicosapentaenoic Acid (analogs & derivatives, chemistry, pharmacology)
• Fatty Acids, Unsaturated (metabolism)
• Humans
• Macrophages (drug effects, metabolism)
• Mice
• RAW 264.7 Cells