Data Sheet 1_Coixol ameliorates dopaminergic neurodegeneration by inhibiting neuroinflammation and protecting mitochondrial function.pdf

Extensive research has revealed that neuroinflammation plays an important role in Parkinson’s disease (PD). Coixol, extracted from Coix lacryma-jobi L., exhibits anti-inflammatory and antioxidant effects in various diseases. However, the effect of coixol on PD remains unclear. The aim of this study is to investigate the effects of coixol in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. Our results show that coixol improves the motor dysfunction and neuronal damage in PD mice by inhibiting neuroinflammation and maintaining mitochondrial function. Moreover, coixol suppressed the overactivation of the nuclear transcription factor κB (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathways and regulated the NLR family pyrin structural domain 3 (NLRP3)/cysteinyl aspartate-specific proteinase-1 (Caspase1)/interleukin-1β (IL-1β) signaling pathway to inhibit neuroinflammation in PD mice. The results show that coixol mitigated reactive oxygen species (ROS)-induced mitochondrial damage, thereby inhibiting the overactivation of the NLRP3 inflammasome. Taken together, we found that coixol alleviates dopaminergic neurodegeneration in PD mice by inhibiting the activation of NF-κB and MAPK signaling pathways to suppress neuroinflammation and protect mitochondrial function from ROS production to regulate NLRP3 inflammasome activation.

大量研究证实，神经炎症在帕金森病（PD）中发挥着关键作用。从薏苡（Coix lacryma-jobi L.）中提取的薏苡素，在多种疾病中均表现出抗炎与抗氧化活性。然而，薏苡素对帕金森病的作用效果仍尚不明确。本研究旨在探究薏苡素在1-甲基-4-苯基-1,2,3,6-四氢吡啶（1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）诱导的帕金森病小鼠模型中的作用。研究结果显示，薏苡素可通过抑制神经炎症、维持线粒体功能，改善帕金森病小鼠的运动功能障碍与神经元损伤。此外，薏苡素可抑制核转录因子κB（NF-κB）与丝裂原活化蛋白激酶（MAPK）信号通路的过度激活，并调控NLR家族pyrin结构域3（NLRP3）/半胱氨酸天冬氨酸特异性蛋白酶-1（Caspase1）/白细胞介素-1β（IL-1β）信号通路，从而抑制帕金森病小鼠的神经炎症反应。研究结果表明，薏苡素可减轻活性氧（ROS）诱导的线粒体损伤，进而抑制NLRP3炎症小体的过度激活。综上，本研究发现，薏苡素可通过抑制NF-κB与MAPK信号通路的激活以减轻神经炎症、维持线粒体功能以抵御活性氧生成，进而调控NLRP3炎症小体的激活，最终改善帕金森病小鼠的多巴胺能神经元变性。