Tryptanthrin inhibits nitric oxide and prostaglandin E(2) synthesis by murine macrophages.
Nitric oxide (NO) and prostaglandins have been implicated in the pathogenesis of several inflammatory diseases. In this study, we investigated the effect of tryptanthrin (6,12-dihydro-6, 12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinctorium, on NO and prostaglandin E(2) production by interferon-gamma and lipopolysaccharide-stimulated murine macrophage-like RAW 264.7 cells. Tryptanthrin markedly inhibited both NO and prostaglandin E(2) production in a dose-dependent manner. Tryptanthrin at 20 microM fully inhibited expression of inducible NO synthase, suggesting that the inhibitory effect on NO synthesis was mediated by inhibited expression of the enzyme. On the other hand, tryptanthrin had no effect on the levels of cyclooxygenase-2 protein, but inhibited cyclooxygenase enzyme activity with a ICM(50) value of 1.5 microM. Thus, tryptanthrin has the dual functions of inhibiting both NO and prostaglandin E(2) production by activated macrophages, suggesting that tryptanthrin exhibits anti-inflammatory properties.
Ishihara
T
T
Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, 702-8006, Okayama, Japan. fujisaki@hayashibara.co.jp
Kohno
K
K
Ushio
S
S
Iwaki
K
K
Ikeda
M
M
Kurimoto
M
M
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism*; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D007527:Isoenzymes; D011799:Quinazolines; C046243:tryptanthrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone