Ahmad Muzamil, Yousuf Seema, Khan M Badruzzaman, Hoda Md Nasrul, Ahmad Abdullah Shafique, Ansari Mubeen Ahmad, Ishrat Tauheed, Agrawal Ashok Kumar, Islam Fakhrul
Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Pharmacol Biochem Behav. 2006 Jan;83(1):150-60. doi: 10.1016/j.pbb.2006.01.005. Epub 2006 Feb 28.
Parkinson's disease (PD) is one of the commonest neurodegenerative diseases, and oxidative stress has been evidenced to play a vital role in its causation. In the present study, we evaluated whether ethanolic extract of Nardostachys jatamansi roots (ENj), an antioxidant and enhancer of biogenic amines, can slow the neuronal injury in a 6-OHDA-rat model of Parkinson's. Rats were treated with 200, 400, and 600 mg/kg body weight of ENj for 3 weeks. On day 21, 2 microl of 6-OHDA (12 microg in 0.01% in ascorbic acid-saline) was infused into the right striatum, while the sham-operated group received 2 microl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioural activity and were sacrificed after 6 weeks for the estimation of lipid peroxidation, reduced glutathione content, the activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase, quantification of catecholamines, dopaminergic D2 receptor binding and tyrosine hydroxylase expression. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by ENj. Lesioning was followed by an increased lipid peroxidation and significant depletion of reduced glutathione content in the substantia nigra, which was prevented with ENj pretreatment. The activities of glutathione-dependent enzymes, catalase and superoxide dismutase in striatum, which were reduced significantly by lesioning, were dose-dependently restored by ENj. A significant decrease in the level of dopamine and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, and both were significantly recovered following ENj treatment. All of these results were exhibited by an increased density of tyrosine hydroxylase immunoreactive (TH-IR) fibers in the ipsilateral striatum of the lesioned rats following treatment with ENj; 6-OHDA injection had induced almost a complete loss of TH-IR fibers. This study indicates that the extract of Jatamansi might be helpful in attenuating Parkinsonism.
帕金森病（PD）是最常见的神经退行性疾病之一，氧化应激已被证明在其病因中起着至关重要的作用。在本研究中，我们评估了匙叶甘松根乙醇提取物（ENj），一种生物胺的抗氧化剂和增强剂，是否能减缓帕金森病6-OHDA大鼠模型中的神经元损伤。大鼠分别用200、400和600mg/kg体重的ENj处理3周。在第21天，将2微升6-OHDA（12微克溶于0.01%抗坏血酸-盐溶液中）注入右侧纹状体，而假手术组接受2微升赋形剂。6-OHDA注射3周后，对大鼠进行神经行为活动测试，并在6周后处死以评估脂质过氧化、还原型谷胱甘肽含量、谷胱甘肽-S-转移酶、谷胱甘肽还原酶、谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶的活性、儿茶酚胺的定量、多巴胺能D2受体结合和酪氨酸羟化酶表达。ENj显著且剂量依赖性地恢复了6-OHDA注射所致的药物诱导旋转增加以及运动活动和肌肉协调性缺陷。损伤后黑质脂质过氧化增加，还原型谷胱甘肽含量显著降低，而ENj预处理可预防这种情况。纹状体中谷胱甘肽依赖性酶、过氧化氢酶和超氧化物歧化酶的活性因损伤而显著降低，ENj剂量依赖性地恢复了这些活性。6-OHDA注射后纹状体中多巴胺及其代谢产物水平显著降低，多巴胺能D2受体数量增加，而ENj治疗后两者均显著恢复。所有这些结果都表现为ENj处理后损伤大鼠同侧纹状体中酪氨酸羟化酶免疫反应性（TH-IR）纤维密度增加；6-OHDA注射几乎导致TH-IR纤维完全丧失。本研究表明，甘松提取物可能有助于减轻帕金森症状。
