title: Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl)serotonin and its derivatives.
abstract: We have reported that N-(p-coumaroyl)serotonin(CS) isolated from safflower oil cake (Carthamus tinctorius L.) inhibits the production of proinflammatory cytokines by endotoxin (LPS)- stimulated human monocytes. In this study, the effects of CS and its three derivatives, N-(trans-cinnamoyl)serotonin (Cin.S), N-(trans-cinnamoyl)tryptamine (Cin.T), and N-(p-coumaroyl)tryptamine (CT) on the production of proinflammatory cytokines were compared. Cin.S possessed radical scavenging activity at a comparable level to CS, while CT and Cin.T exhibited lower activity, suggesting that hydroxyl group in serotonin is essential for the antioxidative activity. CS and CT strongly inhibited the production of proinflammatory cytokines (IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha) from LPS-stimulated human monocytes. However, Cin.S inhibited the production of only IL-1alpha and IL-1beta, and Cin.T inhibited none of these cytokines production. CS and CT markedly inhibited the protein synthesis in monocytes, the inhibitory effect of Cin.S was moderate, and that of Cin.T was quite weak. These results indicate that CS and its derivatives inhibit the production of proinflammatory cytokines through multiple mechanisms.
authors.affiliation: Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya 467-8623, Japan.
authors.forename: Takemasa
authors.initials: T
authors.lastname: Takii
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kawashima
authors.forename: Taku
authors.initials: T
authors.lastname: Chiba
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Masaru
authors.initials: M
authors.lastname: Hayashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hiroma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Inukai
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Shibata
authors.forename: Akito
authors.initials: A
authors.lastname: Nagatsu
authors.forename: Jinnsaku
authors.initials: J
authors.lastname: Sakakibara
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Oomoto
authors.forename: Kunitaka
authors.initials: K
authors.lastname: Hirose
authors.forename: Kikuo
authors.initials: K
authors.lastname: Onozaki
mesh_terms: D000975:Antioxidants / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D014176:Protein Biosynthesis; D012701:Serotonin / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin