TY - JOUR
T1 - Protective effect of verbascoside in activated C6 glioma cells
T2 - Possible molecular mechanisms
AU - Esposito, Emanuela
AU - Dal Toso, Roberto
AU - Pressi, Giovanna
AU - Bramanti, Placido
AU - Meli, Rosaria
AU - Cuzzocrea, Salvatore
PY - 2010/1
Y1 - 2010/1
N2 - 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)-γ, 1 μg/ml and 100 U/ml, respectively). Our results show that the treatment with LPS/IFN-γ 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 μg/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-γ 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.
AB - 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)-γ, 1 μg/ml and 100 U/ml, respectively). Our results show that the treatment with LPS/IFN-γ 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 μg/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-γ 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.
KW - COX-2
KW - Glioma cell line
KW - INOS
KW - NF-κB pathway
KW - Verbascoside
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U2 - 10.1007/s00210-009-0466-0
DO - 10.1007/s00210-009-0466-0
M3 - Article
C2 - 19904526
AN - SCOPUS:74349105180
VL - 381
SP - 93
EP - 105
JO - Naunyn-Schmiedeberg's Archives of Pharmacology
JF - Naunyn-Schmiedeberg's Archives of Pharmacology
SN - 0028-1298
IS - 1
ER -