Wei Zhisheng, Deng Xuemei, Hong Mingfan, Su Quanxi, Liu Aiqun, Huang Yeqing, Yu Qingyun, Peng Zhongxing
Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University No. 19 Nonglinxia Road, Guangzhou 510080, People's Republic of China.
Department of Neurology, The Third Hospital of Wuhan No. 241 Peng Liuyang Road, Wuhan 430060, People's Republic of China.
Int J Clin Exp Med. 2015 Nov 15;8(11):20188-97. eCollection 2015.
High-dose methylprednisolone (MP) is a clinically recommended therapeutic regimen for Multiple Sclerosis (MS), whereas some dreadful complications induced by it remain inevitable. Studies implied that estrogens might play neuroprotective and anti-inflammatory roles in EAE and MS and promote glucocorticoid efficacy. Icariin (ICA), a primary active component of Epimedium extracts, also possesses neuroprotective and estrogen-like effects with less adverse complication than estrogen. However, rare study focuses ICA's effects on MS or EAE.
Our purpose is to determine whether ICA has synergistic effects with MP in treating EAE and explore the possible mechanisms.
C57BL/6 EAE mice were received different dose of ICA combined with MP and single MP treatment. Then, the clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT), Adrenocorticotropic Hormone (ACTH) concentrations were analyzed. Western blot and Flow Cytometry were used to investigate the expression of glucocorticoid receptor (GR) and cell apoptosis.
ICA has cooperative effects with MP in decreasing serum IL-17 and CORT concentrations, up-regulating the expression of GR in cerebral white matter and attenuating the cell apoptosis in spinal cord, especially high-dose ICA combined with MP.
ICA has synergistic effects with MP to ameliorate EAE via modulating hypothalamic-pituitary-adrenal (HPA) function, promoting anti-inflammatory and anti-apoptotic effects. ICA could be considered as a promising therapeutic option for MS.
大剂量甲基泼尼松龙(MP)是临床上推荐用于治疗多发性硬化症(MS)的治疗方案,但其引发的一些严重并发症仍不可避免。研究表明,雌激素可能在实验性自身免疫性脑脊髓炎(EAE)和MS中发挥神经保护和抗炎作用,并增强糖皮质激素的疗效。淫羊藿提取物的主要活性成分淫羊藿苷(ICA)也具有神经保护和类雌激素作用,且不良并发症少于雌激素。然而,很少有研究关注ICA对MS或EAE的影响。
我们的目的是确定ICA在治疗EAE中是否与MP具有协同作用,并探讨其可能的机制。
将C57BL/6 EAE小鼠接受不同剂量的ICA联合MP及单独MP治疗。然后,分析临床评分以及血清白细胞介素-17(IL-17)、皮质酮(CORT)、促肾上腺皮质激素(ACTH)浓度。采用蛋白质免疫印迹法和流式细胞术研究糖皮质激素受体(GR)的表达及细胞凋亡情况。
ICA与MP协同降低血清IL-17和CORT浓度,上调脑白质中GR的表达,并减轻脊髓中的细胞凋亡,尤其是高剂量ICA联合MP时。
ICA与MP协同作用,通过调节下丘脑-垂体-肾上腺(HPA)功能,促进抗炎和抗凋亡作用来改善EAE。ICA可被视为MS的一种有前景的治疗选择。