Ullah Faheem, Liang Huazheng, Niedermayer Garry, Münch Gerald, Gyengesi Erika
Department of Pharmacology, School of Medicine, Western Sydney University, Campbelltown, NSW, Australia.
Department of Neurology, Translational Research Institute of Brain and Brain-like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, China.
Front Neurosci. 2020 Mar 12;14:170. doi: 10.3389/fnins.2020.00170. eCollection 2020.
Chronic glial activation is characterized by an increased number of activated microglia and astroglia; these secrete free radicals and cytotoxic cytokines, subsequently causing neuronal damage. This study investigated the hypothesis that a soy-lecithin based phytosomal curcumin formulation can decrease glial activation in the brains of GFAP-IL6 mice, a model of chronic glial activation, which exhibits gliosis in various regions of the brain. Three doses of Meriva curcumin (MC) (874, 436, and 218 PPM) were fed to 3-month-old GFAP-IL6 and wild-type (WT) mice for 4 weeks. As markers of glial activation, the total numbers of Iba-1 and TSPO microglia and macrophages, and GFAP astrocytes, were determined in the cerebellum and hippocampus by immunohistochemistry and unbiased stereology. Furthermore, the morphology of the glial cells was assessed by confocal microscopy and Sholl analysis. Administration of phytosomal curcumin led to a dose-dependent reduction in neuroinflammatory markers. Phytosomal curcumin (874 PPM) decreased the number of microglia by 26.2% in the hippocampus and by 48% in the cerebellum of the GFAP-IL6 mice compared with the GFAP-IL6 mice on normal food. Additionally, GFAP astrocyte numbers in the hippocampus of the GFAP-IL6 mice were decreased by 42%. The GFAP-IL6 mice exhibited a different microglial morphology to the WT mice, showing an increased soma size and perimeter. This difference was significantly reduced by the 874 PPM phytosomal curcumin dose. Our findings demonstrate that phytosomal curcumin is able to attenuate the inflammatory pathology, and potentially reverse the detrimental effects of chronic glial activation.
慢性胶质细胞激活的特征是活化的小胶质细胞和星形胶质细胞数量增加;这些细胞会分泌自由基和细胞毒性细胞因子,进而导致神经元损伤。本研究探讨了一种基于大豆卵磷脂的姜黄素纳米粒制剂能否减少GFAP-IL6小鼠大脑中的胶质细胞激活这一假说,GFAP-IL6小鼠是慢性胶质细胞激活的模型,其大脑各区域均出现了胶质增生。将三剂Meriva姜黄素(MC)(874、436和218 ppm)喂给3个月大的GFAP-IL6小鼠和野生型(WT)小鼠,持续4周。通过免疫组织化学和无偏立体学方法,测定了小脑和海马中Iba-1和TSPO小胶质细胞及巨噬细胞以及GFAP星形胶质细胞的总数,作为胶质细胞激活的标志物。此外,通过共聚焦显微镜和Sholl分析评估了胶质细胞的形态。给予姜黄素纳米粒导致神经炎症标志物呈剂量依赖性减少。与食用正常食物的GFAP-IL6小鼠相比,姜黄素纳米粒(874 ppm)使GFAP-IL6小鼠海马中的小胶质细胞数量减少了26.2%,小脑中减少了48%。此外,GFAP-IL6小鼠海马中的GFAP星形胶质细胞数量减少了42%。GFAP-IL6小鼠的小胶质细胞形态与WT小鼠不同,其细胞体大小和周长增加。874 ppm的姜黄素纳米粒剂量显著减小了这种差异。我们的研究结果表明,姜黄素纳米粒能够减轻炎症病理,并可能逆转慢性胶质细胞激活的有害影响。