Parkinson's disease (PD) is a progressive neurodegenerative disorder, majorly with symptoms of motor dysfunction. Study was performed to explore the effect of nuclear factor κB (NF-κB) inhibitors against neurobehavioral abnormalities and neuroinflammation in PD. Cost effective in silico approaches of docking-based ligand -target complex predictions and optimal physicochemical properties were utilised to identify lead NF-κB inhibitor using database. Our studies revealed the potential hit Indole-3-carbinol (I3C) which was considered for the next phase, pharmacological validations. Intranigral administration of lipopolysaccharide (LPS) in rats is utilized as a neuroinflmmation model of PD. In the present study it caused impairment in motor functions and learning, and memory as demonstrated in rotarod apparatus, beam balance test, open field test and Morris water maze test. Chronic administration of I3C for 21 days in intranigral LPS treated rats led to a significant improvement in motor functions, coordination, and memory which was associated with a decrease in the activity of inflammatory cytokines such as TNF-α and IL-6. Further, it was found to inhibit NF-κB whose levels increased after LPS administration. Moreover, decreased level of lipid peroxidation and increased activity of reduced glutathione, superoxide dismutase and catalase were observed in cortex and striatum after I3C administration in LPS rats. These results suggest a possible neuroprotective effect of I3C via amelioration of LPS-induced behavioural alterations, oxidative damage and neuroinflammation which in turn is attributed to its potent antioxidant, anti-inflammatory and NF-κB inhibiting property. The effect produced by I3C (50 mg/kg) was found to be comparable with levodopa-carbidopa combination (LD:CD) while, I3C (50 mg/kg) in combination with LD:CD exhibited a potentiating effect in improving motor impairments and cognitive deficit. The results thus depict I3C as a promising agent to delay neurodegeneration of the neurons in PD with improvement in motor functions and cognitive function.

中文翻译：

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Indole-3-carbinol，一种 NF-κB 抑制剂在帕金森病实验范式中的保护作用：计算机和体内研究

帕金森病 (PD) 是一种进行性神经退行性疾病，主要表现为运动功能障碍的症状。进行研究以探索核因子 κB (NF-κB) 抑制剂对 PD 中神经行为异常和神经炎症的影响。使用基于对接的配体-靶标复合物预测和最佳物理化学性质的计算机方法具有成本效益，以使用数据库识别先导 NF-κB 抑制剂。我们的研究揭示了潜在的 Indole-3-carbinol (I3C)，它被考虑用于下一阶段的药理学验证。大鼠中脂多糖 (LPS) 的黑质内给药被用作 PD 的神经炎症模型。在本研究中，它会导致运动功能、学习和记忆受损，如旋转棒装置、梁平衡测试、野外试验和莫里斯水迷宫试验。在黑质内 LPS 治疗的大鼠中长期施用 I3C 21 天导致运动功能、协调性和记忆力的显着改善，这与炎性细胞因子（如 TNF-α 和 IL-6）的活性降低有关。此外，发现它可以抑制在 LPS 给药后水平升高的 NF-κB。此外，在 LPS 大鼠的 I3C 给药后，在皮质和纹状体中观察到脂质过氧化水平降低和还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶的活性增加。这些结果表明 I3C 通过改善 LPS 诱导的行为改变、氧化损伤和神经炎症可能具有神经保护作用，而这又归因于其有效的抗氧化、抗炎和 NF-κB 抑制特性。发现 I3C (50 mg/kg) 产生的效果与左旋多巴-卡比多巴组合 (LD:CD) 相当，而 I3C (50 mg/kg) 与 LD:CD 组合在改善运动障碍和认知缺陷。因此，结果将 I3C 描述为延迟 PD 神经元神经变性并改善运动功能和认知功能的有前途的药物。