Multiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG_35–55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1β, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS.

多发性硬化症 (MS) 被称为一种慢性神经炎症性疾病，其典型特征是免疫介导的脱髓鞘过程，随之而来的轴突损伤和丢失。青藤碱是一种天然生物碱，具有不同的治疗功效，包括抗炎和免疫抑制活性。在这项研究中，确定了青藤碱在 MOG 诱导的 MS 模型中可能的有益作用。青藤碱给了 MOG _35-55- 在 MS 临床症状出现后至免疫后第 30 天以 25 或 100 mg/kg/天的剂量免疫 C57BL/6 小鼠。分析数据表明，青藤碱减轻临床症状的严重程度，并在一定程度上降低组织中促炎细胞因子 IL-1β、IL-6、IL-18、TNFα、IL-17A 的水平，并增加抗炎 IL- 10. 此外，青藤碱除了降低腰脊髓标本中神经炎症、脱髓鞘和轴突损伤和丢失的强度之外，还成功地降低了炎性体 NLRP3、ASC 和半胱天冬酶 1 的组织水平。此外，MOG 免疫后，MBP 的免疫反应性降低和增加 GFAP 和 Iba1，这在施用青藤碱后部分逆转。总体而言，青藤碱降低 EAE 的严重程度，这归因于其减轻小胶质细胞和星形细胞的动员、脱髓鞘和轴突损伤以及抑制神经炎症，其有益作用还与其对炎症小体和细胞焦亡通路的抑制作用有关；这可能对 MS 的原发性进行性表型有潜在益处。