Abstract：
Multiple sclerosis (MS) is an autoimmune disorder characterized by the degeneration of myelin and inflammation in the central nervous system. Trans sodium crocetinate (TSC), a novel synthetic carotenoid compound, possesses antioxidant, anti-inflammatory and neuroprotective effects. This study aimed to evaluate the protective effects of TSC against the development of experimental autoimmune encephalomyelitis (EAE), a well-established model for MS. Female BALB/C57 mice were divided into different groups, including control, EAE, vehicle, TSC-treated (25, 50, and 100 mg/kg, administered via gavage) + EAE, methyl prednisone acetate + EAE, and TSC-treated (100 mg/kg, administered via gavage for 28 days) groups. EAE was induced using MOG35-55, complete Freund\'s adjuvant, and pertussis toxin. In the mice spinal cord tissues, the oxidative markers (GSH and MDA) were measured using spectrophotometry and histological evaluation was performed. Mitophagic pathway proteins (PINK1and PARKIN) and inflammatory factors (IL-1β and TNF-α) were evaluated by western blot. Following 21 days post-induction, EAE mice exhibited weight loss, and the paralysis scores increased on day 13 but recovered after TSC (100 mg/kg) administration on day 16. Furthermore, TSC (50 and 100 mg/kg) reversed the altered levels of MDA and GSH in the spinal cord tissue of EAE mice. TSC (100 mg/kg) also decreased microgliosis, demyelination, and the levels of inflammatory markers IL-1β and TNF-α. Notably, TSC (100 mg/kg) modulated the mitophagy pathway by reducing PINK1 and Parkin protein levels. These findings demonstrate that TSC protects spinal cord tissue against EAE-induced MS through anti-inflammatory, antioxidant, and anti-mitophagy mechanisms.
摘要：
多发性硬化症（MS）是一种自身免疫性疾病，其特征是中枢神经系统的髓磷脂变性和炎症。反式花青酸钠(TSC)，一种新的合成类胡萝卜素化合物，具有抗氧化剂，抗炎和神经保护作用。本研究旨在评估TSC对实验性自身免疫性脑脊髓炎（EAE）发展的保护作用，MS的既定模型将雌性BALB/C57小鼠分为不同的组，包括控制，EAE,车辆,TSC治疗（25、50和100mg/kg，通过管饲法给药）+EAE，醋酸甲基强的松+EAE，和TSC治疗（100mg/kg，通过管饲法给药28天)组。EAE使用MOG35-55，完全弗氏佐剂，和百日咳毒素.在小鼠脊髓组织中，采用分光光度法测定氧化标志物(GSH和MDA),并进行组织学评价.免疫印迹法检测细胞凋亡途径蛋白(PINK1和PARKIN)和炎症因子(IL-1β和TNF-α)。诱导后21天，EAE小鼠表现出体重减轻，并且瘫痪评分在第13天增加，但在第16天TSC（100mg/kg）给药后恢复。此外，TSC（50和100mg/kg）逆转了EAE小鼠脊髓组织中MDA和GSH水平的改变。TSC（100mg/kg）也减少了小胶质细胞增生，脱髓鞘,炎症标志物IL-1β和TNF-α的水平。值得注意的是,TSC（100mg/kg）通过降低PINK1和Parkin蛋白水平来调节线粒体自噬途径。这些发现表明，TSC通过抗炎保护脊髓组织免受EAE诱导的MS，抗氧化剂，和抗线粒体自噬机制。
