Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl)serotonin and its derivatives.
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.
Takii
Takemasa
T
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya 467-8623, Japan.
Kawashima
Sachiko
S
Chiba
Taku
T
Hayashi
Hidetoshi
H
Hayashi
Masaru
M
Hiroma
Hiroyuki
H
Kimura
Hiroaki
H
Inukai
Yoshitaka
Y
Shibata
Yayoi
Y
Nagatsu
Akito
A
Sakakibara
Jinnsaku
J
Oomoto
Yasukazu
Y
Hirose
Kunitaka
K
Onozaki
Kikuo
K
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*
D000975:Antioxidants; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012701:Serotonin; C114774:N-(p-coumaroyl)serotonin