4-dimethylamino-3',4'-dimethoxychalcone downregulates iNOS expression and exerts anti-inflammatory effects.
Reactive oxygen and nitrogen species contribute to the pathophysiology of inflammatory conditions. We have studied the effects of a novel superoxide scavenger, 4-dimethylamino-3', 4'-dimethoxychalcone (CH11) in macrophages and in vivo. CH11 has been shown to inhibit the chemiluminescence induced by zymosan in mouse peritoneal macrophages and the cytotoxic effects of superoxide. In the same cells, the modulation by superoxide of nitric oxide (NO) production in response to zymosan was investigated. CH11 was more effective than the membrane-permeable scavenger Tiron for inhibition of inducible nitric oxide synthase (iNOS) protein expression and nitrite production. We have shown that CH11 inhibited chemiluminescence in vivo, as well as cell migration, and eicosanoid and tumor necrosis factor-alpha (TNF-alpha) levels in the mouse air pouch injected with zymosan. This chalcone derivative also exerted anti-inflammatory effects in the carrageenan paw oedema.
Herencia
F
F
Department of Pharmacology, University of Valencia, Burjasot, Spain.
Ferrándiz
M L
ML
Ubeda
A
A
Guillén
I
I
Dominguez
J N
JN
Charris
J E
JE
Lobo
G M
GM
Alcaraz
M J
MJ
D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002351:Carrageenan; D002599:Chalcone / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D047188:Chalcones; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007249:Inflammation / Q000188:drug therapy*; D008163:Luminescent Measurements; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
C418965:4-dimethylamino-3',4'-dimethoxychalcone; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D013481:Superoxides; D009569:Nitric Oxide; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D002599:Chalcone; D002351:Carrageenan; D015054:Zymosan; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse