Inhibition of nitric oxide (NO.) production in murine macrophages by flavones.
The effect of flavone (2-phenylbenzopyran-4-one) and three amino-substituted flavones on the production of nitrite by murine activated peritoneal macrophages was studied in vitro. Activated peritoneal macrophages obtained from mice pre-treated with concanavalin A (Con A) (in vivo), after exposure in vitro to lipopolysaccharide (LPS) at a concentration of 100 ng/ml, produced nitrite (20.3 +/- 2.5 nmol/10(6) cells), as measured after 24 hr by the Griess reaction. Stimulation of production of nitrite was inhibited by NG-monomethyl-L-arginine, suggesting that nitrite was formed via nitric oxide (NO.) as a product of metabolism of arginine. Stimulation was inhibited by flavone and the aminoflavones (20-100 microM). 3'-amino-4'-hydroxyflavone was the most potent inhibitor of nitrite production. Genistein (5,7-dihydroxy- 3-(4-hydroxy-phenyl)-4H-1-benzopyran-4-one) also inhibited production of nitrite, by a mechanism that appears not to involve protein tyrosine kinases. These results suggest that the flavones can modulate the immune responses and the inflammatory reactions by controlling production of nitric oxide.
Król
W
W
Department of Microbiology and Immunology, Silesian School of Medicine, Zabrze-Rokitnica, Poland.
Czuba
Z P
ZP
Threadgill
M D
MD
Cunningham
B D
BD
Pietsz
G
G
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival; D003208:Concanavalin A / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000032:analysis; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007529:Isoflavones; D008070:Lipopolysaccharides; D009573:Nitrites; D003208:Concanavalin A; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C004742:daidzein; D001120:Arginine; D019833:Genistein; D019001:Nitric Oxide Synthase