ttCH, a selective inhibitor of inducible nitric oxide synthase expression with antiarthritic properties.
In a previous work, we investigated the effects of a series of dimethoxy- and trimethoxychalcone derivatives, with various patterns of fluorination, on nitric oxide production in lipopolysaccharide-stimulated murine RAW 264.7 cells. The present study was designed to determine if 2,4,6-trimethoxy-2'-trifluoromethylchalcone (ttCH) could modulate the production of nitric oxide (NO) and/or prostaglandins in vitro and in vivo. On the mouse macrophage cell line RAW 264.7, ttCH inhibited dose-dependently NO and prostaglandin E(2) production, with IC(50) in the micromolar range. This compound had no direct inhibitory effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 activities. NO reduction was the consequence of inhibition of the expression of iNOS. This compound also exhibited in vivo an inhibitory behaviour on nitrite and prostaglandin E(2) levels. We have assessed the effect of ttCH in the treatment of acute and chronic inflammatory processes such as the mouse carrageenan paw oedema and the rat adjuvant-induced arthritis. The present study demonstrated that ttCH exerts acute and chronic anti-inflammatory effects that may be related with the inhibition of iNOS expression.
Rojas
Javier
J
Departamento de Farmacologi;a, Universidad de Valencia, Avda Vicent Andrés Estellés s/n, Burjasot, Valencia 46100, Spain.
Payá
Miguel
M
Domínguez
José N
JN
Ferrándiz
Ma Luisa
ML
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000517:prevention & control; D015153:Blotting, Western; D002351:Carrageenan; D002460:Cell Line; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006614:Hindlimb / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011859:Radiography; D051381:Rats; D011917:Rats, Inbred Lew
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D002351:Carrageenan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone