The glycosylated phenylpropanoid
verbascoside (VB), isolated from cultured cells of the medicinal plant Syringa vulgaris (Oleaceae), has previously been characterized as an effective scavenger of biologically active
free radicals and an inhibitor of lipid peroxidation. The aim of the present study was to evaluate in a rat
glioma cell line (C6) the effect of VB biotechnologically produced by S. vulgaris plant cell cultures in the regulation of the inflammatory response. We used a model of central nervous system
inflammation induced by bacterial
endotoxin/
cytokine (
lipopolysaccharide (LPS)/
interferon (IFN)-gamma, 1 microg/ml and 100 U/ml, respectively). Our results show that the treatment with LPS/IFN-gamma for 24 h elicited the induction of
inducible nitric oxide synthase (iNOS) activity as determined by NO(x) accumulation in the culture medium. Preincubation with VB (10-100 microg/ml) abrogated the mixed
cytokine-mediated induction of iNOS. The effect was concentration-dependent. Our studies also showed an inhibitory effect of VB on
neuronal nitric oxide synthase expression. Moreover, Western blot analysis showed that this
glycoside prevents specifically the activation of the proinflammatory
enzyme cyclooxygenase (COX)-2 in
glioma cells without simultaneous inhibition of COX-1
enzyme. Moreover, we found that VB reduced the expression of proinflammatory
enzymes in LPS/IFN-gamma through the inhibition of the activation of
nuclear factor kappa B and
mitogen-activated protein kinase signaling pathway. The mechanisms underlying in vitro the neuroprotective properties of VB involve modulation of
transcription factors and consequent altered gene expression, resulting in downregulation of
inflammation. These findings provide support that VB may provide a promising approach for the treatment of oxidative-stress-related
neurodegenerative diseases.