Inhibition of lipopolysaccharide-inducible nitric oxide synthase expression by acteoside through blocking of AP-1 activation

Acteoside is a phenylpropanoid glycoside with antioxidant and anti-inflammatory activities. We isolated acteoside from Buddlejae Flos, which has been used as a traditional medicine to treat conjunctive congestion and sepsis. The effect of acteoside on the expression of the inducible nitric oxide synthase (iNOS) gene was examined in the Raw264.7 macrophage cell line. An acteoside pretreatment significantly inhibited the release of NO in the cells treated with lipopolysaccharide, (LPS). Western blot and RT-PCR analyses revealed that acteoside inhibited the LPS-induced levels of the iNOS protein and mRNA. Activation of the nuclear factor-kappa B (NF-kappa B) and the activator protein-1 (AP-1) is the key step in the signaling pathways mediating iNOS induction. In this study, acteoside selectively suppressed AP-1 activation, which may be essential for iNOS induction in the LPS-treated macrophages. The inhibitory effect of AP-1 activation by acteoside may be associated with the anti-inflammatory effects of Buddlejae Flos. (c) 2005 Elsevier Ireland Ltd. All rights reserved.