Neuroinflammation induced by overactivated glia cells is believed to be a major hallmark of Alzheimer's disease (AD) and a hopeful target against AD. A rhamnoside PL201 was previously reported to promote neurogenesis and ameliorate AD, and in this study, we revealed that PL201 also significantly reduced accumulation of the activated microglia and proinflammatory cytokines in APP/PS1 mice. In vitro, PL201 consistently suppressed the microglia induction of proinflammatory cytokines after stimulation with lipopolysaccharides and Aβ42. Further mechanistic studies demonstrated that PL201 considerably enhanced the expression level and the nuclear translocation of Nrf2, a key regulator of neuroinflammation. Moreover, PL201 effectively stimulated Nrf2 signaling cascade, including upregulation of HO-1 and downregulation of NF-κB pathway. Thus, our findings indicated the anti-neuroinflammatory effect by PL201 in vivo and suggested that PL201 or the like, with multiple functions such as neurogenesis, mitochondria maintenance, and anti-neuroinflammation, could be a promising candidate in AD treatment.

由过度活化的神经胶质细胞诱导的神经炎症被认为是阿尔茨海默氏病（AD）的主要标志，也是对抗AD的有希望的靶标。鼠李糖苷PL201以前被报道可以促进神经发生并改善AD，在这项研究中，我们发现PL201还可以显着减少APP / PS1小鼠中激活的小胶质细胞和促炎细胞因子的积累。体外在用脂多糖和Aβ42刺激后，PL201持续抑制小胶质细胞对促炎细胞因子的诱导。进一步的机理研究表明，PL201大大提高了Nrf2的表达水平和核转运，Nrf2是神经炎症的关键调节剂。此外，PL201有效刺激Nrf2信号级联反应，包括HO-1的上调和NF-κB通路的下调。因此，我们的发现表明PL201具有抗神经炎作用体内 并且提出具有诸如神经发生，线粒体维持和抗神经炎症等多种功能的PL201等可能是AD治疗中的有希望的候选者。