Key Laboratory of Bioactive Materials, Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
Department of Anatomy, School of Medicine, Nankai University, Tianjin 300071, China.
Behav Brain Res. 2020 Apr 6;383:112539. doi: 10.1016/j.bbr.2020.112539. Epub 2020 Feb 4.
Parthenolide (PTL) is a natural compound with anti-inflammatory and antioxidant properties and is an active ingredient extracted from the medicinal plant Tanacetum parthenium. ACT001 is derived from parthenolide and is a fumarate form of dimethylaminomylide (DMAMCL). Its effect is equivalent to that of PTL, but it is more stable in plasma and has lower acquisition costs. Related reports indicate that NLRP3-mediated neuroinflammation is involved in the progression of Parkinson's disease (PD). In our research, we explored whether ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results revealed that ACT001 reduces movement impairment and cognitive deficit in PD mice. In addition, it alleviates dopaminergic neurodegeneration in the nigrostriatal pathway and inhibits oxidative stress, the inflammatory response and activation of the NLRP3 inflammasome in the midbrain of MPTP-induced PD mice. Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by MPTP.
小白菊内酯（PTL）是一种具有抗炎和抗氧化特性的天然化合物，是从药用植物菊蒿中提取的一种活性成分。ACT001 源自小白菊内酯，是二甲氨基丙酰氯（DMAMCL）的富马酸盐形式。其作用与 PTL 相当，但在血浆中更稳定，且购置成本更低。相关报告表明，NLRP3 介导的神经炎症参与了帕金森病（PD）的进展。在我们的研究中，我们探讨了 ACT001 是否能减轻 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠中 NLRP3 介导的神经炎症。我们的结果表明，ACT001 减轻了 PD 小鼠的运动障碍和认知缺陷。此外，它减轻了黑质纹状体通路中的多巴胺能神经退行性变，并抑制了 MPTP 诱导的 PD 小鼠中氧化应激、炎症反应和 NLRP3 炎性小体的激活。此外，它还减轻了黑质纹状体通路中的小胶质细胞激活。总的来说，我们的研究表明，ACT001 减轻了 MPTP 诱导的 PD 小鼠中 NLRP3 介导的神经炎症。
