4-dimethylamino-3 ',4 '-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects

Reactive oxygen and nitrogen species contribute to the pathophysiology of i nflammatory conditions. We have studied the effects of a novel superoxide s cavenger, 4-dimethylamino-3',4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by z ymosan in mouse peritoneal macrophages and the cytotoxic effects of superox ide. In the same cells, the modulation by superoxide of nitric oxide (NO) p roduction in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nit ric oxide synthase (iNOS) protein expression and nitrite production. We hav e shown that CH11 inhibited chemiluminescence in vivo, as well as cell migr ation, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also e xerted anti-inflammatory effects in the carrageenan paw oedema. (C) 2000 El sevier Science Inc.