Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.
Eur J Pharmacol. 2010 Mar 10;629(1-3):40-6. doi: 10.1016/j.ejphar.2009.12.008. Epub 2009 Dec 16.
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.
蛇床子素是一种天然香豆素，具有多种药理学和生物化学用途，被认为具有潜在的治疗应用价值。在这里，我们研究了蛇床子素对实验性自身免疫性脑脊髓炎（EAE），即多发性硬化症模型的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 C57BL/6 小鼠，分别在免疫后第 7 天（亚临床期，早期蛇床子素治疗）和第 13 天（临床期，晚期蛇床子素治疗）开始用蛇床子素治疗，两种治疗均贯穿整个研究过程。检测了体内小鼠血清和脑组织中神经生长因子（NGF）和干扰素γ（IFN-γ）的含量以及体外脾细胞培养上清液中的含量。结果表明，亚临床期开始治疗时，蛇床子素可延缓疾病进程；亚临床期和临床期开始治疗时，均可减轻 EAE 小鼠的临床严重程度；可改善炎症和脱髓鞘，并改善磁共振成像结果。此外，蛇床子素可阻断 EAE 小鼠中 NGF 的减少，并抑制 IFN-γ的增加。这些结果表明，蛇床子素可能是治疗多发性硬化症的一种新的药理学方法。
