Guo Xiaoyuan, Chen Lukui, Li Jianxia
Department of Neurosurgery, Nanjing Medical University, Nanjing, Jiangsu 210000, China.
Department of Neurosurgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210000, China.
ACS Chem Neurosci. 2023 Mar 15;14(6):1119-1125. doi: 10.1021/acschemneuro.2c00668. Epub 2023 Mar 1.
Parkinson's disease (PD) is a common neurodegenerative disorder caused by dopaminergic neuron progressive degeneration. Inhibition of microglial activation may contribute to the treatment and prevention of PD. Plantamajoside (PMS) is a natural compound extracted from plantain seeds. It has a wide range of biological activities, including anti-inflammatory, antioxidative, as well as antitumor effects. However, its possible effects on PD are still unclear. In this study, lipopolysaccharide (LPS) was first injected into the right midbrain substantia nigra (SN) of male C57BL/6 mice to establish the PD mouse model. We found that PMS improved LPS-induced behavioral dysfunction in PD mice. PMS attenuated LPS-induced SN injury in PD mice. PMS could suppress LPS-induced microglial overactivation in PD mice. In addition, MS inhibited LPS-induced activation of the HDAC2/MAPK pathway in PD mice and BV-2 cells. It further revealed that PMS alleviated microglia polarization by inhibiting HDAC2. The limitation of this study was the lack of experiments for investigating the further molecular mechanism and in vivo animal validation, which needs to be further confirmed in the future. Collectively, our data suggested that PMS could serve as a promising drug for PD.
帕金森病（PD）是一种由多巴胺能神经元进行性变性引起的常见神经退行性疾病。抑制小胶质细胞激活可能有助于PD的治疗和预防。车前子苷（PMS）是从车前子种子中提取的一种天然化合物。它具有广泛的生物学活性，包括抗炎、抗氧化以及抗肿瘤作用。然而，其对PD的可能影响仍不清楚。在本研究中，首先将脂多糖（LPS）注射到雄性C57BL/6小鼠的右中脑黑质（SN）中以建立PD小鼠模型。我们发现PMS改善了LPS诱导的PD小鼠行为功能障碍。PMS减轻了LPS诱导的PD小鼠SN损伤。PMS可以抑制LPS诱导的PD小鼠小胶质细胞过度激活。此外，PMS抑制了LPS诱导的PD小鼠和BV-2细胞中HDAC2/MAPK通路的激活。进一步研究表明，PMS通过抑制HDAC2减轻了小胶质细胞极化。本研究的局限性在于缺乏进一步研究分子机制的实验和体内动物验证，未来需要进一步证实。总体而言，我们的数据表明PMS可能是一种有前景的PD治疗药物。
