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黄酮衍生物可预防 Aβ 注射大鼠的识别记忆丧失,并调节线粒体动态向融合的趋势:两种具有不同极性的黄酮类化合物的比较。

Prevention of recognition memory loss and moderation of mitochondrial dynamic tendency toward fusion by flavone derivatives in Aβ-injected rats: a comparison between two flavonoids with different polarity.

机构信息

a Institute of Biochemistry and Biophysics (I.B.B.) , University of Tehran , Tehran , Iran.

b Neuroscience Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.

出版信息

Nutr Neurosci. 2019 Apr;22(4):295-301. doi: 10.1080/1028415X.2017.1384173. Epub 2017 Oct 9.

DOI:10.1080/1028415X.2017.1384173
PMID:28990868
Abstract

Growing evidence sheds light on the use of flavonoids as the promising alternatives for the treatment of chronic conditions, including cancer and neurodegenerative disorders. Accordingly, in the present study, we aimed at evaluating the effects of oral intake of two structurally different flavonoids 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1) and 5,7,4'-trihydroxyflavone (flavone 2) on recognition memory, hippocampal protein level of immediate early gene cFos and mitochondrial dynamic markers in Amyloid β (Aβ)-injected rats. Recognition aspect of memory and level of proteins were measured using novel object recognition test and Western blot, respectively. Our data indicated that even though flavone 1 was more effective than flavone 2 to prevent memory impairment, feeding with both flavones alleviated memory in Aβ-injected rats. Furthermore, in flavones-administered rats, mitochondrial dynamic balancing returned to the control level by the decline in Dynamin-related protein-1 protein level, a known marker for mitochondrial fission, and elevation in protein level of mitochondrial fusion factors Mitofusins 1 and 2. In parallel with behavior results, flavone 1 was more effectual on mitochondrial dynamic moderating. The more neuroprotective effects of flavone 1 could be attributed to its methylated structure leading to crossing of the blood-brain barrier with ease and metabolic stability and bioactivity.

摘要

越来越多的证据表明,类黄酮可作为治疗慢性疾病(包括癌症和神经退行性疾病)的有前途的替代品。因此,在本研究中,我们旨在评估口服两种结构不同的类黄酮 5-羟基-6,7,4'-三甲氧基黄酮(黄酮 1)和 5,7,4'-三羟基黄酮(黄酮 2)对β淀粉样蛋白(Aβ)注射大鼠的识别记忆、海马即刻早期基因 cFos 蛋白水平和线粒体动态标志物的影响。使用新物体识别测试和 Western blot 分别测量记忆的识别方面和蛋白质水平。我们的数据表明,尽管黄酮 1比黄酮 2更有效地预防记忆障碍,但两种黄酮的喂养均可减轻 Aβ 注射大鼠的记忆障碍。此外,在给予黄酮的大鼠中,通过下调已知的线粒体分裂标志物 Dynamin-related protein-1 蛋白水平和上调线粒体融合因子 Mitofusins 1 和 2 的蛋白水平,使线粒体动态平衡恢复到对照水平。与行为结果平行的是,黄酮 1 对线粒体动态调节更有效。黄酮 1 的神经保护作用更强,可能归因于其甲基化结构,使其易于穿过血脑屏障,具有代谢稳定性和生物活性。

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