Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tuebingen, Tuebingen, Germany.
J Cell Mol Med. 2013 Dec;17(12):1566-76. doi: 10.1111/jcmm.12124. Epub 2013 Sep 5.
Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti-inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short-term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated β-amyloid deposition, plaque-associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin-nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases.
阿尔茨海默病（AD）是最常见的神经退行性疾病，也是痴呆的主要原因。这种多因素疾病在临床上表现为进行性行为和认知障碍，并在神经病理学上表现为β-淀粉样蛋白聚集、过度磷酸化的 tau 和神经炎症。冬凌草甲素是从中国草药冬凌草中分离出来的二萜类化合物，具有多种生物学特性，特别是抗炎和神经调节活性。在 APP/PS1 转基因 AD 动物模型中研究了冬凌草甲素的潜在治疗作用。冬凌草甲素悬浮在羧甲基纤维素中或负载在纳米结构乳液中，通过口服或注射给药。在实验治疗之前、期间和之后，对这些转基因小鼠及其未处理的同窝小鼠进行行为测试。在相对短期的 10 天治疗后，取出小鼠的脑组织进行免疫组织化学检测。结果表明，口服和注射冬凌草甲素均可显著减轻转基因小鼠大脑中的β-淀粉样蛋白沉积、斑块相关 APP 表达和小胶质细胞激活。此外，注射冬凌草甲素纳米乳液可改善筑巢（一种重要的社交行为）和社交互动缺陷。此外的体外研究表明，冬凌草甲素可有效减轻巨噬细胞和小胶质细胞系的炎症反应。我们的研究结果表明，冬凌草甲素可能被认为是人类 AD 或其他神经退行性疾病的一种有前途的治疗选择。
