Ghalami Jamileh, Baluchnejad Mojarad Tourandokht, Mansouri Monireh, Khamse Safoura, Roghani Mehrdad
Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Neurophysiology Research Center, Shahed University, Tehran, Iran.
Basic Clin Neurosci. 2021 Jan-Feb;12(1):43-56. doi: 10.32598/bcn.12.6.88.7. Epub 2021 Jan 1.
Parkinson's Disease (PD) presentations comprise frequent movement disorders in the elderly with various symptoms consisting of motor and non-motor complications. Paeonol is a phenolic chemical agent that has shown antioxidant and anti-inflammatory effects in different disorders and promising effects on metabotropic glutamate receptors (mGluR)- and GABAA-mediated neurotransmission. In this research, we tried to show the neuroprotective potential of paeonol in rat PD model induced by intrastriatal 6-hydroxydopamine (6-OHDA).
Rats with intrastriatal 6-OHDA lesioning received with paeonol at a dosage of 100 mg/kg/d for one week. In the end, some biomarkers of oxidative stress, apoptosis, and astrogliosis in nigral and striatal tissues were evaluated in addition to behavioral and Tyrosine Hydroxylase (TH) immunohistochemical analysis.
The obtained data showed that paeonol alleviates apomorphine-induced rotations and reduces the delay time to initiate and the total time in the narrow beam test. However, its beneficial behavioral effect vanished after intracerebroventricular administration of mGluR III or GABAA receptor antagonists. Moreover, paeonol significantly restored striatal malondialdehyde, tissue levels of reactive oxygen species, the activity of the protective and vital enzymes consisting of superoxide dismutase and catalase, Glial Fibrillary Acidic Protein (GFAP), DNA fragmentation, phosphor apoptosis signal-regulating kinase 1, and nigral aquaporin 4 with no significant and proper change of nitrite, interleukin-1β, inducible nitric oxide synthase, and angiotensin II. Additionally, paeonol prevented injury and reduced tyrosine hydroxylase-containing neurons in the midbrain nigral tissue.
These obtained findings evidently designate neuroprotective property of paeonol in 6-OHDA murine model of PD that is exerted via easing of oxidative stress, apoptosis, astrogliosis, and its advantageous effect is to some extent mediated via mGluR III/GABAA pathway.
帕金森病（PD）表现为老年人常见的运动障碍，伴有各种症状，包括运动和非运动并发症。丹皮酚是一种酚类化学物质，在不同疾病中显示出抗氧化和抗炎作用，对代谢型谷氨酸受体（mGluR）和GABAA介导的神经传递有显著影响。在本研究中，我们试图证明丹皮酚在纹状体内注射6-羟基多巴胺（6-OHDA）诱导的大鼠PD模型中的神经保护潜力。
纹状体内注射6-OHDA损伤的大鼠接受剂量为100mg/kg/d的丹皮酚治疗，持续一周。最后，除了行为学和酪氨酸羟化酶（TH）免疫组化分析外，还评估了黑质和纹状体组织中氧化应激、细胞凋亡和星形胶质细胞增生的一些生物标志物。
获得的数据表明，丹皮酚可减轻阿扑吗啡诱导的旋转，并减少在窄光束试验中开始的延迟时间和总时间。然而，在脑室内注射mGluR III或GABAA受体拮抗剂后，其有益的行为效应消失。此外，丹皮酚显著恢复了纹状体丙二醛、活性氧物质的组织水平、由超氧化物歧化酶和过氧化氢酶组成的保护和重要酶的活性、胶质纤维酸性蛋白（GFAP）、DNA片段化、磷酸化凋亡信号调节激酶1以及黑质水通道蛋白4，而亚硝酸盐、白细胞介素-1β、诱导型一氧化氮合酶和血管紧张素II没有显著和适当的变化。此外，丹皮酚可预防中脑黑质组织的损伤并减少含酪氨酸羟化酶的神经元。
这些获得的发现明显表明丹皮酚在6-OHDA小鼠PD模型中具有神经保护特性，其通过减轻氧化应激、细胞凋亡、星形胶质细胞增生来发挥作用，并且其有益作用在一定程度上是通过mGluR III/GABAA途径介导的。
