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

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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 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.

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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

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Authors and Affiliations

  1. IRCCS Centro Neurolesi “Bonino-Pulejo”, Messina, Italy

    Emanuela Esposito, Placido Bramanti & Salvatore Cuzzocrea

  2. I.R.B. srl, Altavilla Vicentina, Italy

    Roberto Dal Toso & Giovanna Pressi

  3. Department of Experimental Pharmacology, University of Naples Federico II, Naples, Italy

    Rosaria Meli

  4. Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Messina, Italy

    Salvatore Cuzzocrea

  5. Institute of Pharmacology, School of Medicine, University of Messina, via C. Valeria, Torre Biologica, Policlinico Universitario, 98123, Messina, Italy

    Salvatore Cuzzocrea

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  1. Emanuela Esposito
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  2. Roberto Dal Toso
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  3. Giovanna Pressi
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  4. Placido Bramanti
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  6. Salvatore Cuzzocrea
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Correspondence to Salvatore Cuzzocrea.

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Esposito, E., Dal Toso, R., Pressi, G. et al. Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms. Naunyn-Schmied Arch Pharmacol 381, 93–105 (2010). https://doi.org/10.1007/s00210-009-0466-0

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