Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms
Protective effect of verbascoside in activated C6 glioma cells: possible molecular mechanisms
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DOI：
10.1007/s00210-009-0466-0
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Cuzzocrea, Salvatore
中科院分区：
文献类型：
--
作者：
Esposito, Emanuela;Dal Toso, Roberto;Cuzzocrea, Salvatore
糖基化苯丙素类毛蕊花糖苷（VB），从药用植物丁香（木犀科）的培养细胞中分离，以前已被表征为生物活性自由基的有效清除剂和脂质过氧化的抑制剂。本研究的目的是在大鼠胶质瘤细胞系（C6）中评估由S.寻常植物细胞培养在炎症反应的调节。我们使用由细菌内毒素/细胞因子（脂多糖（LPS）/干扰素（IFN）-γ，分别为1 μ g/ml和100 U/ml）诱导的中枢神经系统炎症模型。我们的研究结果表明，LPS/IFN-γ处理24小时引起诱导型一氧化氮合酶（iNOS）活性的诱导，确定NO（x）在培养基中的积累。用VB（10-100 μ g/ml）预孵育废除了混合的精氨酸介导的iNOS诱导。该效应呈浓度依赖性。我们的研究还表明，VB对神经元型一氧化氮合酶表达的抑制作用。此外，蛋白质印迹分析表明，这种糖苷特异性地阻止神经胶质瘤细胞中促炎酶环氧合酶（考克斯）-2的活化，而不同时抑制考克斯-1酶。此外，我们发现VB通过抑制核因子κ B和丝裂原活化蛋白激酶信号通路的激活来降低LPS/IFN-γ中促炎酶的表达。VB的体外神经保护特性的机制涉及转录因子的调节和随后改变的基因表达，导致炎症的下调。这些研究结果支持VB可能为治疗氧化应激相关的神经退行性疾病提供一种有前途的方法。
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 mu g/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 mu g/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.