Chrysoeriol potently inhibits the induction of nitric oxide synthase by blocking AP-1 activation
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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-κB (NF-κB) 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.
Keywords:Anti-inflammatory activity AP-1 Chrysoeriol iNOS Nitric oxide
Dulbecco’s modified Eagle’s medium
Extracellular signal-regulated kinase
fetal calf serum
inducible nitric oxide synthase
c-Jun N-terminal kinase
S16 ribosomal protein
sodium dodecyl sulfate
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This work was supported in part by a grant from the Regional University Research Program (E-00216; Kang K.W.) funded by Korea Research Foundation and the Plant Diversity Research Center 21st Century Frontier Research Program funded by the Korean Ministry of Science and Technology (Grant No. PF0320505-00; Woo E.).
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