1,1-Dimethylallylcoumarins potently suppress both lipopolysaccharide- and interferon-gamma-induced nitric oxide generation in mouse macrophage RAW 264.7 cells.
We investigated the suppressive effects of 16 coumarin-related compounds on both lipopolysaccharide (LPS)- and interferon (IFN)-gamma-induced nitric oxide (NO) generation in a mouse macrophage cell line, RAW 264.7. Notably, coumarins possessing prenyl unit(s) were found to be highly active, a tendency consistent with our previous study. Among the coumarins tested, 1,1-dimethylallylcoumarins showed the highest inhibitory activity. Western blotting analysis revealed that they inhibited NO generation by suppressing inducible NO synthase (iNOS) protein expression. Our ongoing studies suggest that coumarins are prominent natural compounds that attenuate excessive and prolonged NO generation at inflammatory sites.
Murakami
A
A
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama, Japan.
Gao
G
G
Omura
M
M
Yano
M
M
Ito
C
C
Furukawa
H
H
Takahashi
D
D
Koshimizu
K
K
Ohigashi
H
H
D000818:Animals; D002460:Cell Line; D003374:Coumarins / Q000494:pharmacology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D009387:Neoprene / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship
D003374:Coumarins; D008070:Lipopolysaccharides; C016077:prenyl; D009569:Nitric Oxide; D007371:Interferon-gamma; D009387:Neoprene; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse