Abstract：
Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1β, IL-18, CD16, and TNF-α). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.
摘要：
石杉碱甲(HupA)是一种天然的乙酰胆碱酯酶抑制剂(AChEI),选择性以及可逆性,并且可以对某些神经退行性疾病表现出显著的治疗效果。它也有利于减少实验性自身免疫性脑脊髓炎（EAE）的神经损伤和神经炎症，多发性硬化症（MS）的经典模型。然而,HupA是否可以直接调节少突胶质细胞的分化和成熟，促进髓鞘再生，以前还没有研究。在这项研究中,我们分析了HupA对铜松（CPZ）诱导的MS脱粉模型的潜在保护作用。发现HupA显着减弱了焦虑样行为，以及增强CPZ小鼠的运动和认知功能。它还减少了CPZ小鼠的脱髓鞘和轴突损伤。此外，在CPZ小鼠中，HupA增加了各种抗炎细胞因子（Arg1，CD206）的mRNA水平，同时降低了不同促炎细胞因子（iNOS，IL-1β,IL-18、CD16和TNF-α)。美加明,一种烟碱乙酰胆碱受体拮抗剂，可以有效逆转HupA的影响。因此,我们的结论是HupA主要通过减轻脱髓鞘和神经炎症来发挥对多发性硬化的治疗作用。
