Tian Yuan-Yuan, An Li-Jia, Jiang Lan, Duan Yan-Long, Chen Jun, Jiang Bo
School of Environmental and Biological Science and Technology, Dalian University of Technology, Dalian, Liaoning, 116024, China.
Life Sci. 2006 Dec 23;80(3):193-9. doi: 10.1016/j.lfs.2006.09.010. Epub 2006 Sep 20.
Inflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia, the resident immune cells in the central nervous system, are pivotal in the inflammatory reaction. Activated microglia can induce expression of inducible nitric-oxide synthase (iNOS) and release significant amounts of nitric oxide (NO) and TNF-alpha, which can damage the dopaminergic neurons. Catalpol, an iridoid glycoside, contained richly in the roots of Rehmannia glutinosa, was found to be neuroprotective in gerbils subjected to transient global cerebral ischemia. But the effect of catalpol on inflammation-mediated neurodegeneration has not been examined. In this study, microglia in mesencephalic neuron-glia cultures were activated with lipopolysaccharide (LPS) and the aim of the study was to examine whether catalpol could protect dopaminergic neurons from LPS-induced neurotoxicity. The results showed that catalpol significantly reduced the release of reactive oxygen species (ROS), TNF-alpha and NO after LPS-induced microglial activation. Further, catalpol attenuated LPS-induced the expression of iNOS. As determined by immunocytochemical analysis, pretreatment by catalpol dose-dependently protected dopaminergic neurons against LPS-induced neurotoxicity. These results suggest that catalpol exerts its protective effect on dopaminergic neurons by inhibiting microglial activation and reducing the production of proinflammatory factors. Thus, catalpol may possess therapeutic potential against inflammation-related neurodegenerative diseases.
炎症在帕金森病（PD）的发病机制中起重要作用。小胶质细胞作为中枢神经系统中的常驻免疫细胞，在炎症反应中起关键作用。活化的小胶质细胞可诱导诱导型一氧化氮合酶（iNOS）的表达，并释放大量一氧化氮（NO）和肿瘤坏死因子-α（TNF-α），这些物质会损害多巴胺能神经元。梓醇是一种环烯醚萜苷，在地黄根中含量丰富，已发现在遭受短暂全脑缺血的沙鼠中具有神经保护作用。但梓醇对炎症介导的神经退行性变的影响尚未得到研究。在本研究中，用脂多糖（LPS）激活中脑神经元-胶质细胞培养物中的小胶质细胞，本研究的目的是检测梓醇是否能保护多巴胺能神经元免受LPS诱导的神经毒性。结果表明，梓醇能显著降低LPS诱导的小胶质细胞活化后活性氧（ROS）、TNF-α和NO的释放。此外，梓醇减弱了LPS诱导的iNOS表达。通过免疫细胞化学分析确定，梓醇预处理能剂量依赖性地保护多巴胺能神经元免受LPS诱导的神经毒性。这些结果表明，梓醇通过抑制小胶质细胞活化和减少促炎因子的产生，对多巴胺能神经元发挥保护作用。因此，梓醇可能具有治疗炎症相关神经退行性疾病的潜力。
