de Rus Jacquet Aurélie, Timmers Michael, Ma Sin Ying, Thieme Andrew, McCabe George P, Vest Jay Hansford C, Lila Mary Ann, Rochet Jean-Christophe
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.
Plants for Human Health Institute, Department of Food Bioprocessing and Nutrition Sciences, North Carolina State University, Kannapolis, NC 28081, USA.
J Ethnopharmacol. 2017 Jul 12;206:408-425. doi: 10.1016/j.jep.2017.02.021. Epub 2017 Feb 15.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta and the presence in surviving neurons of Lewy body inclusions enriched with aggregated forms of the presynaptic protein α-synuclein (aSyn). Although current therapies provide temporary symptomatic relief, they do not slow the underlying neurodegeneration in the midbrain. In this study, we analyzed contemporary herbal medicinal practices used by members of the Lumbee tribe to treat PD-related symptoms, in an effort to identify safe and effective herbal medicines to treat PD.
The aims of this study were to (i) document medicinal plants used by Lumbee Indians to treat PD and PD-related symptoms, and (ii) characterize a subset of plant candidates in terms of their ability to alleviate neurotoxicity elicited by PD-related insults and their potential mechanisms of neuroprotection.
Interviews of Lumbee healers and local people were carried out in Pembroke, North Carolina, and in surrounding towns. Plant samples were collected and prepared as water extracts for subsequent analysis. Extracts were characterized in terms of their ability to induce activation of the nuclear factor E2-related factor 2 (Nrf2) antioxidant response in cortical astrocytes. An extract prepared from Sambucus caerulea flowers (elderflower extract) was further examined for the ability to induce Nrf2-mediated transcription in induced pluripotent stem cell (iPSC)-derived astrocytes and primary midbrain cultures, to ameliorate mitochondrial dysfunction, and to alleviate rotenone- or aSyn-mediated neurotoxicity.
The ethnopharmacological interviews resulted in the documentation of 32 medicinal plants used to treat PD-related symptoms and 40 plants used to treat other disorders. A polyphenol-rich extract prepared from elderflower activated the Nrf2-mediated antioxidant response in cortical astrocytes, iPSC-derived astrocytes, and primary midbrain cultures, apparently via the inhibition of Nrf2 degradation mediated by the ubiquitin proteasome system. Furthermore, the elderflower extract rescued mitochondrial functional deficits in a neuronal cell line and alleviated neurotoxicity elicited by rotenone and aSyn in primary midbrain cultures.
These results highlight potential therapeutic benefits of botanical extracts used in traditional Lumbee medicine, and they provide insight into mechanisms by which an elderflower extract could suppress neurotoxicity elicited by environmental and genetic PD-related insults.
帕金森病（PD）是一种神经退行性疾病，其特征是黑质致密部多巴胺能神经元丧失，以及存活神经元中存在富含突触前蛋白α-突触核蛋白（aSyn）聚集形式的路易小体包涵体。尽管目前的疗法能提供暂时的症状缓解，但并不能减缓中脑潜在的神经退行性变。在本研究中，我们分析了卢比部落成员用于治疗PD相关症状的当代草药疗法，以努力识别治疗PD的安全有效的草药。
本研究的目的是（i）记录卢比印第安人用于治疗PD及PD相关症状的药用植物，以及（ii）根据植物候选物减轻PD相关损伤引发的神经毒性的能力及其潜在的神经保护机制，对其中一部分植物进行特性描述。
在北卡罗来纳州彭布罗克及周边城镇对卢比部落的治疗师和当地人进行了访谈。采集植物样本并制备成水提取物用于后续分析。提取物根据其在皮质星形胶质细胞中诱导核因子E2相关因子2（Nrf2）抗氧化反应激活的能力进行特性描述。对从接骨木花制备的提取物（接骨木花提取物）进一步研究其在诱导多能干细胞（iPSC）衍生的星形胶质细胞和原代中脑培养物中诱导Nrf2介导的转录、改善线粒体功能障碍以及减轻鱼藤酮或aSyn介导的神经毒性的能力。
民族药理学访谈记录了32种用于治疗PD相关症状的药用植物和40种用于治疗其他疾病的植物。从接骨木花制备的富含多酚的提取物在皮质星形胶质细胞、iPSC衍生的星形胶质细胞和原代中脑培养物中激活了Nrf2介导的抗氧化反应，显然是通过抑制泛素蛋白酶体系统介导的Nrf2降解。此外，接骨木花提取物挽救了神经元细胞系中的线粒体功能缺陷，并减轻了原代中脑培养物中鱼藤酮和aSyn引发的神经毒性。
这些结果突出了传统卢比医学中使用的植物提取物的潜在治疗益处，并提供了关于接骨木花提取物抑制环境和遗传PD相关损伤引发的神经毒性的机制的见解。
