N‐Octadecanoyl‐5‐Hydroxytryptamide Suppresses Lipopolysaccharide‐Induced Inflammatory Responses in Macrophages
Authors: Fernandes Patricia Dias , Giorno Thais Biondino Sardella , da Silva Moreira Iris Gonçalvez , Rezende Claudia Moraes 
Published: June 2021

The C18 5‐HT, a new Nβ‐alkanoyl‐5‐hydroxytryptamide is naturally found in the surface wax of coffee beans (Speer et al., 2006) and has antinociceptive effect (Giorno et al., 2018). Some amides of the serotonin class demonstrated an anti‐inflammatory effect by inhibiting the expression of caspases participants in inflammatory process (Meijerink et al., 2013)The C18 5‐HT, a new Nβ‐alkanoyl‐5‐hydroxytryptamide is naturally found in the surface wax of coffee beans (Speer et al., 2006) and has antinociceptive effect (Giorno et al., 2018). Some amides of the serotonin class demonstrated an anti‐inflammatory effect by inhibiting the expression of caspases participants in inflammatory process (Meijerink et al., 2013). In this study, we have investigated the in vitro anti‐inflammatory activity of C18 5‐HT, a new fatty acid amide of serotonin. RAW 264.7 murine macrophage cells stimulated with 1 μg/mL of E. coli lipopolysaccharide (LPS) were treated with different concentrations of C18 5‐HT (0.01, 0.03, 0.1, 0.3, 1 and 3 μM) for 24 h or 48h to evaluated cell viability by MTT (3‐(4,5‐dimethylthiazol‐2‐yl) ‐2,5‐difenltetrazolium). These LPS‐stimulated cells were also treated with 5‐HT C18 (0.1, 0.3, or 1 μM) to assess nitric oxide (NO) levels and cytokines (TNF‐α, IL‐1β, IL‐6 and IL‐10). The results showed that the cell viability of cells was significantly reduced only after 24h incubation with 3 μM of C18 5‐HT. LPS caused fold increase in NO production (49.7 ± 1.3 μM). Pretreatment of LPS‐activated cells with C18 5‐HT significantly suppressed NO production at 0.3 and 1 μM concentrations (39.9 ± 2.6* μM and 32.5 ± 3.1* μM, respectively versus vehicle‐treated group=49.7 ± 1.3 μM). C18 5‐HT also decreased the levels of TNF‐α (0.3 μM= 1,448.1± 376.6*; 1 μM= 1,083.1 ± 298.4* versus vehicle‐treated group = 2,231.9 ± 256.5 pg/mL and IL‐1 β (0.1 μM= 2,699 ± 597.3; 0.3 μM= 1,265.4 ± 438.8; 1 μM= 647.4 ± 187.5 versus vehicle‐treated group=5632.4 ± 1324.2 pg/mL) in a dose‐dependent manner. The compound also decreased significantly IL‐6 levels in the 1 μM concentration, promoting a reduction of 58.3 % when compared to vehicle‐treated group (1 μM=197.6 ± 46.7* versus vehicle‐treated group=474.4 ± 128.3 pg/mL) and increased the level of IL‐10 at 1 μM concentration (1 μM=4,393.5 ± 723.7* versus vehicle‐treated group= 2,514.2 ± 373.1 pg/mL). We can conclude that the treatment with C18 5‐HT did not reduce the viability of cells and that C18 5‐HT effectively inhibits pro‐inflammatory markers such as NO and cytokines (TNF‐α, IL‐1β and IL‐6). Data suggest that this substance could be used as new prototype for the development of new anti‐inflammatory drugs.

Support or Funding Information

Financial support: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brasil (CAPES)/Finance Code 001, CNPq and FAPERJ.

Technical Support: Alan Minho

Animal donation: Institute Vital Brazil

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.