A-252, Pharmacology Lab II, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, India.
National Centre for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health, Parel, Mumbai, Maharashtra, 400 012, India.
Brain Res Bull. 2020 Jul;160:150-161. doi: 10.1016/j.brainresbull.2020.03.003. Epub 2020 Mar 5.
Parkinson's disease (PD) is an age associated, progressive and a second most common neurodegenerative disease. It is caused due to degeneration of dopaminergic neurons in substantia nigra (SN). Various studies implicate mitochondrial dysfunction, oxidative stress, altered degradation of misfolded proteins in PD pathogenesis. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is reported to possess a number of biological activities viz. anti-oxidant, anti-inflammatory etc. The focus of our study was to assess the neuroprotective potential of UA against the rotenone induced pathophysiological alterations. In this study rats were subjected to stereotaxic bilateral injection of rotenone (12 μg/μl) in SN. Further, they were treated per-orally with UA (5 and 10 mg/kg) for 30 days. During the study, neurobehavioral tests comprising Rota-rod, Open field and Barnes maze (BMT) were conducted. At the end of 30 days, the antioxidant (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammatory (TNF-α) parameters, mitochondrial complex I, mitochondrial biogenesis (MB) and immunohistochemical analysis (TH positive neurons, Glial Fibrillary Acidic Protein (GFAP)) was performed. The results exhibited significant amelioration in the motor deficits by UA which can be attributed to the protection of TH positive neurons from degeneration. A significant improvement in the cognitive function due to UA was observed in BMT. Biochemically, the oxidative stress and inflammation triggered by rotenone was significantly diminished by UA. It also significantly obviated the complex I inhibition and promoted MB. The preliminary results thus firmly advocate the neuroprotective potential of UA to prevent rotenone induced neurotoxicity in rats.
帕金森病（PD）是一种与年龄相关的进行性疾病，也是第二常见的神经退行性疾病。它是由于黑质（SN）中的多巴胺能神经元退化引起的。各种研究表明，线粒体功能障碍、氧化应激、错误折叠蛋白的降解改变与 PD 的发病机制有关。熊果酸（UA）是一种天然五环三萜羧酸，据报道具有多种生物学活性，如抗氧化、抗炎等。我们研究的重点是评估 UA 对鱼藤酮诱导的病理生理改变的神经保护潜力。在这项研究中，大鼠接受了 SN 双侧立体定向注射鱼藤酮（12μg/μl）。此外，它们还接受了 UA（5 和 10mg/kg）的口服治疗，为期 30 天。在研究过程中，进行了神经行为测试，包括转棒、旷场和巴恩斯迷宫（BMT）。在 30 天结束时，进行了抗氧化（还原型谷胱甘肽、超氧化物歧化酶、过氧化氢酶和脂质过氧化）、炎症（TNF-α）参数、线粒体复合物 I、线粒体生物发生（MB）和免疫组织化学分析（TH 阳性神经元、胶质纤维酸性蛋白（GFAP））。结果表明，UA 显著改善了运动缺陷，这可归因于 UA 对 TH 阳性神经元免受退化的保护。UA 还观察到 BMT 中认知功能的显著改善。生物化学分析表明，UA 显著减轻了鱼藤酮引发的氧化应激和炎症。它还显著缓解了复合物 I 的抑制作用并促进了 MB。初步结果因此有力地主张 UA 具有预防鱼藤酮诱导的大鼠神经毒性的神经保护潜力。
