Neuroinflammation, glial activation, and oxidative injury are the main pathological mechanisms of demyelination in multiple sclerosis (MS). Arbutin, a natural polyphenol compound, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has not been studied in the experimental animal models of MS. In the present study, the efficiency of arbutin on lysolecthin (LPC)-induced local demyelination model was investigated. Demyelination was induced by micro-injection of 2 μl LPC (1%) into the rat optic chiasm and the treated group received daily injection of arbutin (50 mg/kg, i.p) during 2 weeks. Visual-evoked potential (VEP) recordings were used to functionally assess the visual pathway. Gene expression analysis was done to evaluate the arbutin effect on the inflammatory, stress oxidative-related mediators, and myelin markers. The myelin-specific staining was performed to assess demyelination and GFAP staining as an astrocyte marker. We found that arbutin significantly reduced P1-latency of VEPs waves and demyelination at 7 and 14 days post-demyelination. Arbutin decreased inflammatory cytokines (IL-1B, IL-17, TNF-α) and iNOS mRNA expression level. In addition, the expression level of anti-inflammatory cytokine (IL-10) and antioxidant mediators (Nrf-2 and HO-1) was enhanced by arbutin treatment. Arbutin increased MBP and Olig2 expression levels in demyelination context. Finally, arbutin attenuated GFAP as an astrocyte marker. Finally, this study demonstrates that arbutin improves functional recovery and myelin repair in the demyelinated optic chiasm through attenuation of inflammation, astrocyte activation, and oxidative stress. These findings might open new promising avenues for treating demyelinating disorders such as multiple sclerosis.

Graphical abstract

神经炎症，神经胶质细胞活化和氧化损伤是多发性硬化症（MS）脱髓鞘的主要病理机制。熊果苷是一种天然的多酚化合物，具有抗氧化，抗炎和神经保护的特性，其治疗潜力尚未在MS实验动物模型中进行研究。在本研究中，研究了熊果素对溶血菌素（LPC）诱导的局部脱髓鞘模型的效率。通过将2μlLPC（1％）微注射到大鼠视交叉中来诱导脱髓鞘，并且治疗组在2周内每天注射熊果苷（50 mg / kg，ip）。视觉诱发电位（VEP）记录用于功能性评估视觉通路。进行了基因表达分析以评估熊果苷对炎症，应激氧化相关介体的作用，和髓磷脂标记。进行髓磷脂特异性染色以评估脱髓鞘作用和作为星形胶质细胞标记的GFAP染色。我们发现，熊果苷可在脱髓鞘后7天和14天显着降低VEPs波和脱髓鞘的P1潜伏期。熊果苷可降低炎性细胞因子（IL-1B，IL-17，TNF-α）和iNOS mRNA表达水平。此外，熊果苷处理可提高抗炎细胞因子（IL-10）和抗氧化剂介质（Nrf-2和HO-1）的表达水平。熊果苷在脱髓鞘的情况下增加了MBP和Olig2表达水平。最后，熊果苷减弱了作为星形胶质细胞标记物的GFAP。最后，这项研究表明，熊果苷通过减轻炎症，星形胶质细胞活化和氧化应激，改善脱髓鞘性视神经干的功能恢复和髓鞘修复。

图形概要