Tryptanthrin inhibits nitric oxide and prostaglandin E-2 synthesis by murine macrophages

Nitric oxide (NO) and prostaglandins have been implicated in the pathogenes is of several inflammatory diseases. In this study, we investigated the eff ect of tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline), an antimicrobial and antitumoral plant compound isolated from Porigonum tinct orium, on NO and prostaglandin E-2 production by interferon-gamma and lipop olysaccharide-stimulated murine macrophage-like RAW 264.7 cells. Tryptanthr in markedly inhibited both NO and prostaglandin E-2 production in a dose-de pendent manner. Tryptanthrin at 20 muM fully inhibited expression of induci ble NO synthase, suggesting that the inhibitory effect on NO synthesis was mediated by inhibited expression of the enzyme. On the other hand, tryptant hrin had no effect on the levels of cyclooxygenase-2 protein, but inhibited cyclooxygenase enzyme activity with a ICM50 value of 1.5 muM. Thus, trypta nthrin has the dual functions of inhibiting both NO and prostaglandin E-2 p roduction by activated macrophages, suggesting that tryptanthrin exhibits a nti-inflammatory properties. (C) 2000 Elsevier Science B.V. All rights rese rved.