Interdisciplinary Brain Research Centre, Faculty of Medicine, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
Drug Dev Res. 2018 Aug;79(5):218-224. doi: 10.1002/ddr.21436.
Preclinical Research & Development Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects approximately 10 million people worldwide. The risk of developing PD and similar neurodegenerative disorders increases with age and an estimated 4% people are diagnosed with the disease before reaching the age of 50. Oxidative stress, cytotoxicity, and mitochondrial dysfunction are common features exhibited in the development of PD. The 6-hyroxydopamine (6-OHDA) model of PD is one of the most well characterized and studied models of the disease. 6-OHDA, a neurotoxin, can induce most characteristic features of the disease, including mitochondrial dysfunction in-vivo and in-vitro. SH-SY5Y is a neuroblastoma cell line of human origin that has been used for dose response studies on PD in the past. Based on previous data, we have used SH-SY5Y cells as an in-vitro model of PD to analyse the phytomedicinal potential of perillyl alcohol (PA), a monoterpenoid obtained from essential oils of various plants such as sage, peppermint and lavender. We have found that pretreatment with PA (10 μM and 20 μM) mitigated 6-OHDA (150 μM) induced cytotoxicity in a dose-dependent manner. We observed marked restoration of cell viability and mitochondrial membrane potential (MMP) as well as reduced reactive oxygen species generation, Cytochrome c immunofluorescence and DNA fragmentation after treatment with PA. On the basis of on our data, we have come to the conclusion that PA demonstrates sufficient neuroprotective activity to provide new avenues in therapy of PD and its apparent target being restoration of MMP can lead to better understanding of the disease.
临床前研究与开发帕金森病（PD）是第二常见的神经退行性疾病，影响着全球约 1000 万人。PD 及类似神经退行性疾病的发病风险随着年龄的增长而增加，估计有 4%的人在 50 岁之前被诊断出患有该疾病。氧化应激、细胞毒性和线粒体功能障碍是 PD 发展过程中的常见特征。6-羟多巴胺（6-OHDA）PD 模型是该疾病最具特征和研究最充分的模型之一。6-OHDA，一种神经毒素，可诱导疾病的大多数特征，包括体内和体外的线粒体功能障碍。SH-SY5Y 是人源神经母细胞瘤细胞系，过去曾用于 PD 的剂量反应研究。基于先前的数据，我们使用 SH-SY5Y 细胞作为 PD 的体外模型，分析了来自各种植物（如鼠尾草、薄荷和薰衣草）精油的单萜化合物——紫苏醇（PA）的植物药潜力。我们发现，PA（10 μM 和 20 μM）预处理以剂量依赖的方式减轻了 6-OHDA（150 μM）诱导的细胞毒性。在用 PA 处理后，我们观察到细胞活力和线粒体膜电位（MMP）明显恢复，活性氧生成、细胞色素 c 免疫荧光和 DNA 片段减少。基于我们的数据，我们得出结论，PA 表现出足够的神经保护活性，为 PD 的治疗提供了新的途径，其明显的靶点是恢复 MMP，这可以使我们更好地了解该疾病。
