Effect of Aryl-Cyclohexanones and their Derivatives on Macrophage Polarization In Vitro.

Autor: Lubschinski TL; Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Pollo LAE; Department of Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Mohr ETB; Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., da Rosa JS; Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Nardino LA; Department of Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Sandjo LP; Department of Chemistry, CFM, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Biavatti MW; Department of Pharmaceutical Sciences, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil., Dalmarco EM; Department of Clinical Analysis, Center of Health Sciences, Federal University of Santa Catarina, Florianópolis, Santa Catarina, 88040-970, Brazil. eduardo.dalmarco@ufsc.br.
Jazyk: angličtina
Zdroj: Inflammation [Inflammation] 2022 Aug; Vol. 45 (4), pp. 1612-1630. Date of Electronic Publication: 2022 Mar 05.
DOI: 10.1007/s10753-022-01646-9
Abstrakt: Macrophages are critical in both tissue homeostasis and inflammation, and shifts in their polarization have been indicated as pivotal for the resolution of inflammatory processes. Inflammation is a complex and necessary component of the immune response to stimuli that are harmful to host homeostasis and is regulated by cellular and molecular events that remain a source of ongoing investigation. Among the compounds studied that have potential against autoimmune and inflammatory diseases, cannabinoids are currently highlighted. In this work, nineteen aryl-cyclohexanones diesters and their derivatives were synthesized based on the aryl-cyclohexane skeleton of phytocannabinoids, such as cannabidiol (CBD), and were evaluated for their anti-inflammatory and macrophage polarization potential. The results showed that Compound 4 inhibited the production of nitric oxide in RAW 264.7 macrophages. Furthermore, it reduced the levels of pro-inflammatory cytokines IL-12p70, TNF-α, IFN-γ, MCP-1, and IL-6 while, at the same time, was able to increase the production of anti-inflammatory cytokines IL-4, IL-10, and IL-13. Compound 4 also reduced macrophage apoptosis, increased the expression of the CD206 (mannose receptor) and at the same time, decreased the expression of CD284 (TLR-4 receptor) on the surface of these cells. Finally, it increased the phagocytic capacity and inhibited the phosphorylation of the p65 of NF-kβ. In conclusion, Compound 4, identified as diethyl-4-hydroxy-2-(4-methoxyphenyl)-4-methyl-6-oxocyclohexane-1-3-dicarboxylate, showed significant anti-inflammatory effect, while demonstrating the ability to transform phenotypically macrophages from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory). This led us to hypothesize that the main mechanism of anti-inflammatory effect of this molecule is linked to its immune modulation capacity.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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