Cellular and Molecular Neurobiology Laboratory, Department of Life Science and Bioinformatics, Assam University, Silchar, Assam, 788011, India.
Department of Zoology, Pandit Deendayal Upadhyaya Adarsha Mahavidyalaya (PDUAM), Bishwanath Chariali, Assam, India.
Exp Brain Res. 2022 Jan;240(1):113-122. doi: 10.1007/s00221-021-06237-y. Epub 2021 Oct 11.
Although the etiology of Parkinson's disease (PD) is poorly understood, studies in animal models revealed loss of dopamine and the dopaminergic neurons harbouring the neurotransmitter to be the principal cause behind this neuro-motor disorder. Neuroinflammation with glial cell activation is suggested to play a significant role in dopaminergic neurodegeneration. Several biomolecules have been reported to confer dopaminergic neuroprotection in different animal models of PD, owing to their anti-inflammatory potentials. Garcinol is a tri-isoprenylated benzophenone isolated from Garcinia sp. and accumulating evidences suggest that this molecule could provide neuroprotection by modulating oxidative stress and inflammation. However, direct evidence of dopaminergic neuroprotection by garcinol in the pre-clinical model of PD is not yet reported. The present study aims to investigate whether administration of garcinol in the MPTP mouse model of PD may ameliorate the cardinal motor behavioural deficits and prevent the loss of dopaminergic neurons. As expected, garcinol blocked the parkinsonian motor behavioural deficits which include akinesia, catalepsy, and rearing anomalies in the mice model. Most importantly, the degeneration of dopaminergic cell bodies in the substantia nigra region was significantly prevented by garcinol. Furthermore, garcinol reduced the inflammatory marker, glial fibrillary acidic protein, in the substantia nigra region. Since glial hyperactivation-mediated inflammation is inevitably associated with the loss of dopaminergic neurons, our study suggests the anti-inflammatory role of garcinol in facilitating dopaminergic neuroprotection in PD mice. Hence, in the light of the present study, it is suggested that garcinol is an effective anti-parkinsonian agent to block motor behavioural deficits and dopaminergic neurodegeneration in PD.
虽然帕金森病（PD）的病因尚不清楚，但动物模型研究表明，多巴胺的丧失和携带这种神经递质的多巴胺能神经元的丧失是这种神经运动障碍的主要原因。神经炎症和神经胶质细胞的激活被认为在多巴胺能神经退行性变中起重要作用。已经有几种生物分子被报道在不同的 PD 动物模型中具有多巴胺能神经保护作用，这是由于它们的抗炎潜力。藤黄酚是从藤黄属植物中分离出来的三异戊烯基二苯甲酮，越来越多的证据表明，这种分子可以通过调节氧化应激和炎症来提供神经保护。然而，藤黄酚在 PD 的临床前模型中是否具有多巴胺能神经保护作用的直接证据尚未报道。本研究旨在探讨藤黄酚在 MPTP 诱导的 PD 小鼠模型中是否能改善主要运动行为缺陷并防止多巴胺能神经元的丢失。正如预期的那样，藤黄酚阻断了帕金森病小鼠模型中的帕金森运动行为缺陷，包括运动迟缓、僵住和异常站立。最重要的是，藤黄酚显著阻止了多巴胺能细胞体在黑质区域的退化。此外，藤黄酚降低了黑质区域的炎症标志物胶质纤维酸性蛋白。由于神经胶质细胞的过度激活介导的炎症不可避免地与多巴胺能神经元的丢失有关，我们的研究表明藤黄酚的抗炎作用有助于 PD 小鼠的多巴胺能神经保护。因此，根据本研究，藤黄酚是一种有效的抗帕金森药物，可以阻断 PD 中的运动行为缺陷和多巴胺能神经退行性变。
