Chrysoeriol potently inhibits the induction of nitric oxide synthase by blocking AP-1 activation.
Chrysoeriol is a flavonoid with antioxidant and anti-inflammatory activities. Despite the large number of studies performed on its biological activities, no clear picture of its mode of action has emerged. In the present study, we isolated chrysoeriol from the leaves of Digitalis purpurea (foxglove), and studied its effect on the induction of the inducible nitric oxide synthase (iNOS) gene, and the mechanism of this induction in Raw264.7 macrophages. Chrysoeriol pretreatment potently inhibited the release of NO in the cells treated with lipopolysaccharide (LPS), and Western blot and RT-PCR analyses revealed that chrysoeriol inhibited the LPS-induced inductions of iNOS gene. Moreover, it is known that the activations of nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) are crucial steps in the transcriptional activation of the iNOS gene. Here, we found that chrysoeriol selectively suppressed AP-1 activation, and that activation of AP-1 is likely to be essential for iNOS induction in LPS-treated macrophages. This presumed inhibitory effect on AP-1 activation by chrysoeriol may be associated with its potent NO blocking and anti-inflammatory effects.
Choi
Doo-Youn
DY
Research Center for Proteineous Materials, Chosun University, Gwangju, 501-759, South Korea.
Lee
Jeong Yong
JY
Kim
Mi-Ran
MR
Woo
Eun-Rhan
ER
Kim
Yoon Gyoon
YG
Kang
Keon Wook
KW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D004070:Digitalis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047309:Flavones; D005419:Flavonoids / Q000378:metabolism / Q000502:physiology*; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009841:Oligonucleotides / Q000737:chemistry; D018515:Plant Leaves / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009841:Oligonucleotides; D013778:Tetrazolium Salts; D013844:Thiazoles; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C022616:thiazolyl blue; C007054:chrysoeriol