Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF-α, IL-1α, IL-1β, and IL-6 by endotoxin-stimulated human blood monocytes

We have reported that N-(p-coumaroyl) serotinin (CS) and its derivatives with antioxidative activity are present in safflower seeds. As reactive oxygen species (ROS) are implicated in the signaling of lipololysaccharide (LPS), we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocytes in vitro. CS at 50-200 mu M reduced tumor necrosis factor (TNF), interleukin-l (IL-1), and IL-6 activities in the culture supernatants from LPS-stimuiated human blood monocytes without cytotoxicity, ELISA assay revealed that the production of TNF-alpha IL-1 alpha, IL-1 beta, and IL-6 was inhibited by CS. Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS. NF-kappa B activation was also inhibited by CS. These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes, and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappa B activation.