Attenuation of experimental autoimmune encephalomyelitis in C57 BL/6 mice by osthole, a natural coumarin

Attenuation of experimental autoimmune encephalomyelitis in C57 BL/6 mice by osthole, a natural coumarin
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蛇床子素(一种天然香豆素)可减轻 C57 BL/6 小鼠实验性自身免疫性脑脊髓炎。

DOI:
10.1016/j.ejphar.2009.12.008
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发表时间:
2010-03-10
影响因子:
5
通讯作者:
Hu, Xueqiang
Hu, Xueqiang
中科院分区:
医学2区
文献类型:
--
作者:
Chen, Xiaohong;Pi, Rongbiao;Hu, Xueqiang

文献摘要

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蛇床子素是一种天然香豆素,已知具有多种药理学和生物化学用途,并被认为具有潜在的治疗应用。本研究旨在探讨蛇床子素对多发性硬化模型实验性自身免疫性脑脊髓炎(EAE)中枢神经系统脱髓鞘的影响及其机制。用髓鞘少突胶质细胞糖蛋白35-55氨基酸肽免疫的C57 BL/6小鼠在免疫后第7天用蛇床子素处理(7 p.i.,亚临床期,早期蛇床子素治疗)和p.i.(临床期,晚期蛇床子素治疗),并且两种疗法在整个研究中持续。测定了小鼠体内血清、脑组织及体外脾细胞培养上清中神经生长因子(NGF)和γ-干扰素(IFN-γ)的含量。结果表明,蛇床子素在亚临床期开始治疗时延缓疾病进程,在亚临床期和临床期开始治疗时减轻EAE小鼠的临床严重程度,改善炎症和脱髓鞘,并改善磁共振成像的结果。此外,蛇床子素阻断了EAE小鼠中NGF的减少并抑制了IFN-γ的增加。这些结果提示蛇床子素可能成为治疗多发性硬化的一种新的药理学途径。(C)2009 Elsevier B. V.保留所有权利。
Osthole, a natural coumarin, is known to have a variety of pharmacological and biochemical uses and is considered to have potential therapeutic applications. Here we examined the effects of osthole on the central nervous system demyelination in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis and its mechanism(s). C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with osthole at day 7 post immunization (7 p.i., subclinical periods, early osthole treatment) and day 13 p.i. (clinical periods, late osthole treatment) respectively and both therapies continued throughout the study. The content of nerve growth factor (NGF) and interferon gamma (IFN-gamma) in the sera and brain of mice in vivo as well as the splenocytes Culture supernatants in vitro were detected. The results showed that osthole retarded the disease process when the therapy was initiated at subclinical periods, attenuated the clinical severity of EAE mice when the therapy was initiated at both subclinical and clinical periods, ameliorated inflammation and demyelination and improved the outcomes of magnetic resonance imaging. In addition, osthole blocked the reduction of NGF and suppressed IFN-gamma increase in EAE mice. These results suggested that osthole might be a new pharmacological approach to treat multiple sclerosis. (C) 2009 Elsevier B.V. All rights reserved.