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Multiple mechanisms involved in the inhibition of proinflammatory cytokine production from human monocytes by N-(p-coumaroyl)serotonin and its derivatives

2003; Elsevier BV; Volume: 3; Issue: 2 Linguagem: Inglês

10.1016/s1567-5769(02)00207-2

1878-1705

Takemasa Takii, Sachiko Kawashima, Taku Chiba, Hidetoshi Hayashi, Masaru Hayashi, Hiroyuki Hiroma, Hiroaki Kimura, Yoshitaka Inukai, Yayoi Shibata, Akito Nagatsu, Jinnsaku Sakakibara, Yasukazu Oomoto, Kunitaka Hirose, Kikuo Onozaki,

Cannabis and Cannabinoid Research

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-1α, IL-1β, IL-6, IL-8, and TNF-α) from LPS-stimulated human monocytes. However, Cin.S inhibited the production of only IL-1α and IL-1β, 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.