In this study, we aim to assess the phytomedicinal potential of perillyl alcohol (PA), a dietary monoterpenoid, in a unilateral 6-hydroxydopamine (6-OHDA) lesion rat model of Parkinson’s disease (PD). We observed that PA supplementation alleviated behavioural abnormalities such as loss of coordination, reduced rearing and motor asymmetry in lesioned animals. We also observed that PA-treated animals exhibited reduced oxidative stress, DNA fragmentation and caspase 3 activity indicating alleviation of apoptotic cell death. We found reduced mRNA levels of pro-apoptotic regulator BAX and pro-inflammatory mediators IL18 and TNFα in PA-treated animals. Further, PA treatment successfully increased mRNA and protein levels of Bcl2, mitochondrial biogenesis regulator PGC1α and tyrosine hydroxylase (TH) in lesioned animals. We observed that PA treatment blocked BAX and Drp1 translocation to mitochondria, an event often associated with the inception of apoptosis. Further, 6-OHDA exposure reduced expression of electron transport chain complexes I and IV, thereby disturbing energy metabolism. Conversely, expression levels of both complexes were upregulated with PA treatment in lesioned rats. Finally, we found that protein levels of Nrf2, the transcription factor responsible for antioxidant gene expression, were markedly reduced in cytosolic and nuclear fraction on 6-OHDA exposure, and PA increased expression of Nrf2 in both fractions. We believe that our data hints towards PA having the ability to provide cytoprotection in a hemiparkinsonian rat model through alleviation of motor deficits, oxidative stress, mitochondrial dysfunction and apoptosis.

中文翻译：

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紫苏醇通过减轻氧化应激缓解帕金森病单侧6-OHDA病变模型中的行为变化并限制细胞死亡和线粒体变化。

在这项研究中，我们旨在评估帕金森氏病（PD）的单侧6-羟基多巴胺（6-OHDA）病变大鼠模型中的膳食单萜类化合物紫苏醇（PA）的植物药潜力。我们观察到，补充PA可以减轻患病动物的行为异常，例如失去协调能力，减少饲养和运动不对称。我们还观察到，用PA治疗的动物表现出降低的氧化应激，DNA片段化和caspase 3活性，表明减轻了凋亡细胞的死亡。我们发现在PA治疗的动物中，促凋亡调节剂BAX和促炎介质IL18和TNFα的mRNA水平降低。此外，PA处理成功地增加了患病动物的Bcl2，线粒体生物发生调节因子PGC1α和酪氨酸羟化酶（TH）的mRNA和蛋白水平。我们观察到，PA处理可阻止BAX和Drp1易位至线粒体，这通常与细胞凋亡的发生有关。另外，6-OHDA暴露降低了电子传输链复合物I和IV的表达，从而干扰了能量代谢。相反，用PA处理在病变大鼠中两种复合物的表达水平均上调。最后，我们发现6-OHDA暴露时，胞质和核组分中Nrf2（负责抗氧化剂基因表达的转录因子）的蛋白水平显着降低，而PA均增加了Nrf2在这两个组分中的表达。我们认为，我们的数据提示PA具有通过减轻运动功能缺陷，氧化应激，线粒体功能障碍和细胞凋亡在半帕金森病大鼠模型中提供细胞保护的能力。