Husain Ibraheem, Akhtar Mohd, Vohora Divya, Abdin Malik Zainul, Islamuddin Mohammad, Akhtar Mohd Jawaid, Najmi Abul Kalam
Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
Department of Biotechnology, Faculty of Science, Jamia Hamdard (Hamdard University), New Delhi, 110062, India.
Neurochem Res. 2017 Aug;42(8):2404-2416. doi: 10.1007/s11064-017-2264-2. Epub 2017 Apr 18.
Recent attention is focused on the impact of diet on health and mental well-being. High-salt and cholesterol diet (HSCD) is known to be associated with neuroinflammation which is the predominant factor for neurodegenerative disease like Alzheimer disease (AD). In the present study, we examined the neuroprotective potential of rosuvastatin, an HMG-CoA reductase inhibitor against HSCD induced neuroinflammation and cognitive impairment. Our results demonstrated that HSCD-induced cognitive impairment as determined by Morris water maze (MWM) task. HSCD also activated nuclear factor kappaB (NF-kB) signaling pathway. The cytokine response was measured using a cytometric bead-based assay quantified by flow cytometry. Treatment with rosuvastatin decreased the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-α) and increased interleukin-10 (IL-10) in a dose-dependent manner. Our results also demonstrated that the rosuvastatin modulates neuronal cell death by inhibiting the overexpression of NF-kB in the CA1 region of hippocampus. In addition, molecular docking study of rosuvastatin indicated high affinity and tighter binding capacity for the active site of the NF-kB. These results suggest that HSCD-triggered inflammatory response and cognitive impairment may be associated with NF-κB signaling pathway. Therefore, treatment with rosuvastatin could be a potential new therapeutic strategy for sporadic dementia of AD.
近期，人们的注意力集中在饮食对健康和心理健康的影响上。高盐和高胆固醇饮食（HSCD）已知与神经炎症有关，而神经炎症是诸如阿尔茨海默病（AD）等神经退行性疾病的主要因素。在本研究中，我们检测了瑞舒伐他汀（一种HMG-CoA还原酶抑制剂）对HSCD诱导的神经炎症和认知障碍的神经保护潜力。我们的结果表明，通过莫里斯水迷宫（MWM）任务确定HSCD诱导了认知障碍。HSCD还激活了核因子κB（NF-κB）信号通路。使用基于细胞计数微珠的检测方法并通过流式细胞术进行定量来测量细胞因子反应。瑞舒伐他汀治疗以剂量依赖的方式降低了一氧化氮（NO）、肿瘤坏死因子α（TNF-α）的产生，并增加了白细胞介素-10（IL-10）。我们的结果还表明，瑞舒伐他汀通过抑制海马体CA1区NF-κB的过表达来调节神经元细胞死亡。此外，瑞舒伐他汀的分子对接研究表明其对NF-κB的活性位点具有高亲和力和更强的结合能力。这些结果表明，HSCD引发的炎症反应和认知障碍可能与NF-κB信号通路有关。因此，瑞舒伐他汀治疗可能是散发性AD痴呆的一种潜在新治疗策略。
