Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 381, Issue 1, pp 93–105

Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms

  • Emanuela Esposito
  • Roberto Dal Toso
  • Giovanna Pressi
  • Placido Bramanti
  • Rosaria Meli
  • Salvatore Cuzzocrea
ORIGINAL ARTICLE

DOI: 10.1007/s00210-009-0466-0

Cite this article as:
Esposito, E., Dal Toso, R., Pressi, G. et al. Naunyn-Schmied Arch Pharmacol (2010) 381: 93. doi:10.1007/s00210-009-0466-0

Abstract

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 NOx 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.

Keywords

VerbascosideNF-κB pathwayGlioma cell lineiNOSCOX-2

Abbreviations

PPGs

Phenylpropanoid glycosides

PPs

Phenylpropanoids

VB

Verbascoside

NO

Nitric oxide

NOS

Nitric oxide synthase

CNS

Central nervous system

NF-κB

Nuclear factor kappa B

MAPKs

Mitogen-activated protein kinases

DMEM

Dulbecco’s modified essential medium

LPS

Lipopolysaccharide

IFN

Interferon

MDA

Malondialdehyde

COX

Cyclooxygenase

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Emanuela Esposito
    • 1
  • Roberto Dal Toso
    • 2
  • Giovanna Pressi
    • 2
  • Placido Bramanti
    • 1
  • Rosaria Meli
    • 3
  • Salvatore Cuzzocrea
    • 1
    • 4
    • 5
  1. 1.IRCCS Centro Neurolesi “Bonino-Pulejo”MessinaItaly
  2. 2.I.R.B. srlAltavilla VicentinaItaly
  3. 3.Department of Experimental PharmacologyUniversity of Naples Federico IINaplesItaly
  4. 4.Department of Clinical and Experimental Medicine and Pharmacology, School of MedicineUniversity of MessinaMessinaItaly
  5. 5.Institute of Pharmacology, School of MedicineUniversity of MessinaMessinaItaly