Wang Wei-Wei, Lu Lin, Bao Tian-Hao, Zhang Hong-Miao, Yuan Jing, Miao Wei, Wang Shu-Fen, Xiao Zhi-Cheng
Key Laboratory of Stem Cells and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, Yunnan, People's Republic of China.
Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People's Republic of China.
J Mol Neurosci. 2016 Feb;58(2):210-20. doi: 10.1007/s12031-015-0660-0. Epub 2015 Oct 29.
Scutellarin, a flavonoid extracted from an herbal medication (Erigeron breviscapus Hand-Mazz), has been shown to protect neurons against damage and to promote neurogenesis, and thus has therapeutic potential in the treatment of a variety of neurodegenerative diseases. Since neural stem cells (NSCs) could differentiate into myelin-producing oligodendrocytes, we speculate that scutellarin could also be used to treat multiple sclerosis (MS). In the current study, we examined potential effects of scutellarin using a mouse model of MS. Briefly, adult C57BL/6 mice exposed to cuprizone (8 mg/day through diet, for 6 consecutive weeks) randomly received scutellarin (50 mg/kg/day) or vehicle for 10 consecutive days. In the scutellarin-treated group, rotarod testing at the end of the treatment showed significant improvement of motor function (increased time to fall); myelin basic protein (MBP) staining of the corpus callosum revealed decreased demyelination; TUNEL staining followed by Nestin or Sox2 staining revealed increased number of NSCs and decreased rate of NSC apoptosis in the subventricular zone (SVZ) of the lateral ventricles (LV). In a series of experiments using cultured NSCs subjected to cuprizone injury, we confirmed the protective effects of scutellarin. At 30 μM, scutellarin increased the commitment of NSCs to the oligodendrocyte and neuronal lineages, as evidenced by NG2 chondroitin sulfate proteoglycan (NG2) and doublecortin (DCX) staining. Differentiation into astrocytes (as revealed by glial fibrillary acidic protein (GFAP) staining) was decreased. Maturation of the NSCs committed to the oligodendrocyte lineage, as evidenced by oligodendrocyte marker O4 antibody (O4) staining and MBP staining, was also promoted by scutellarin. Further analysis revealed that scutellarin might suppress the phosphorylation of p38 in cuprizone-induced NSCs. In summary, scutellarin could alleviate motor deficits in a mouse model for MS, possibly by inhibiting NSC apoptosis and promoting differentiation of NSCs to myelin-producing oligodendrocytes.
灯盏花素是从一种草药（短葶飞蓬，Hand-Mazz）中提取的黄酮类化合物，已被证明可保护神经元免受损伤并促进神经发生，因此在治疗多种神经退行性疾病方面具有治疗潜力。由于神经干细胞（NSCs）可分化为产生髓磷脂的少突胶质细胞，我们推测灯盏花素也可用于治疗多发性硬化症（MS）。在本研究中，我们使用MS小鼠模型研究了灯盏花素的潜在作用。简要地说，成年C57BL/6小鼠暴露于双环己酮草酰二腙（通过饮食给予8mg/天，连续6周），随机连续10天接受灯盏花素（50mg/kg/天）或赋形剂。在灯盏花素治疗组中，治疗结束时的转棒试验显示运动功能有显著改善（跌落时间增加）；胼胝体的髓鞘碱性蛋白（MBP）染色显示脱髓鞘减少；TUNEL染色后进行巢蛋白或Sox2染色显示侧脑室（LV）室下区（SVZ）的神经干细胞数量增加，神经干细胞凋亡率降低。在一系列使用遭受双环己酮草酰二腙损伤的培养神经干细胞的实验中，我们证实了灯盏花素的保护作用。在30μM时，灯盏花素增加了神经干细胞向少突胶质细胞和神经元谱系的分化，硫酸软骨素蛋白聚糖（NG2）和双皮质素（DCX）染色证明了这一点。向星形胶质细胞的分化（通过胶质纤维酸性蛋白（GFAP）染色显示）减少。灯盏花素还促进了向少突胶质细胞谱系分化的神经干细胞的成熟，少突胶质细胞标志物O4抗体（O4）染色和MBP染色证明了这一点。进一步分析表明，灯盏花素可能抑制双环己酮草酰二腙诱导的神经干细胞中p38的磷酸化。总之，灯盏花素可减轻MS小鼠模型中的运动缺陷，可能是通过抑制神经干细胞凋亡并促进神经干细胞向产生髓磷脂的少突胶质细胞分化来实现的。
