Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid β-induced rat model of Alzheimer's disease: underlying mechanisms
Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid β-induced rat model of Alzheimer's disease: underlying mechanisms
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DOI：
10.1007/s11011-019-00481-6
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发表时间：
2019-12-01
影响因子：
3.6
通讯作者：
Roghani, Mehrdad
中科院分区：
文献类型：
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作者：
Baluchnejadmojarad, Tourandokht;Mohamadi-Zarch, Seyed-Mahdi;Roghani, Mehrdad
阿尔茨海默病（Alzheimer's disease，AD）是一种最常见的神经退行性淀粉样蛋白疾病，具有进行性认知和记忆能力退化。尽管做出了许多努力，但对于AD还不存在决定性的治疗。番红花醛是番红花精油的活性成分，具有抗氧化、抗炎和抗细胞凋亡的特性。在这项研究中，在海马内淀粉样蛋白β（A β（1-40））诱导的AD大鼠模型中评估了番红花醛对认知缺陷的可能有益作用。番红花醛每日口服给药。（0.025、0.1和0.2 ml/kg）术后1周，最后除了评估氧化应激、炎症和细胞凋亡的参与外，还评估了学习和记忆。研究结果显示，对β-淀粉样蛋白微量注射的大鼠进行番红花醛处理，剂量依赖性地改善了Y-迷宫、新物体辨别、被动回避和8臂放射臂迷宫任务中的认知。此外，番红花醛还能降低海马组织中丙二醛（MDA）、活性氧（ROS）、蛋白羰基、白细胞介素1 β（IL 1 β）的含量（IL-1 β）、白细胞介素6（IL-6）、肿瘤坏死因子α（TNF α）、核因子-κ B（NF-kB）、凋亡生物标志物（包括胱天蛋白酶3和DNA片段化）、胶质细胞酸性蛋白（GFAP）、髓过氧化物酶（MPO）、和乙酰胆碱酯酶（AChE）活性，提高超氧化物歧化酶（SOD）活性和线粒体膜电位（MMP），而对亚硝酸盐，过氧化氢酶活性和谷胱甘肽（GSH）无显著影响。此外，番红花醛防止由于淀粉样蛋白β（1-40）引起的CA 1神经元损失。总之，番红花醛治疗海马内β淀粉样蛋白（1-40）-微量注射大鼠可以通过神经元保护和在分子水平上通过改善细胞凋亡，氧化应激，炎症，胆碱酯酶活性，中性粒细胞浸润，以及通过保护线粒体完整性来预防学习和记忆衰退。
Alzheimer's disease (AD) is the most prevalent neurodegenerative amyloid disorder with progressive deterioration of cognitive and memory skills. Despite many efforts, no decisive therapy yet exists for AD. Safranal is the active constituent of saffron essential oil with antioxidant, anti-inflammatory, and anti-apoptotic properties. In this study, the possible beneficial effect of safranal on cognitive deficits was evaluated in a rat model of AD induced by intrahippocampal amyloid beta (A beta (1-40)). Safranal was daily given p.o. (0.025, 0.1, and 0.2 ml/kg) post-surgery for 1 week and finally learning and memory were evaluated in addition to assessment of the involvement of oxidative stress, inflammation, and apoptosis. Findings showed that safranal treatment of amyloid beta -microinjected rats dose-dependently improved cognition in Y-maze, novel-object discrimination, passive avoidance, and 8-arm radial arm maze tasks. Besides, safranal attenuated hippocampal level of malondialdehyde (MDA), reactive oxygen species (ROS), protein carbonyl, interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF alpha), nuclear factor-kappa B (NF-kB), apoptotic biomarkers including caspase 3 and DNA fragmentation, glial fibrillary acidic protein (GFAP), myeloperoxidase (MPO), and acetylcholinesterase (AChE) activity and improved superoxide dismutase (SOD) activity and mitochondrial membrane potential (MMP) with no significant effect on nitrite, catalase activity, and glutathione (GSH). Furthermore, safranal prevented CA1 neuronal loss due to amyloid beta (1-40). In summary, safranal treatment of intrahippocampal amyloid beta(1-40)-microinjected rats could prevent learning and memory decline via neuronal protection and at a molecular level through amelioration of apoptosis, oxidative stress, inflammation, cholinesterase activity, neutrophil infiltration, and also by preservation of mitochondrial integrity.