甜菜素对味精诱导的小鼠ADHD的改善作用及Nrf2与TLR4/NFκB/p53相互作用的调节

IF 3 Q2 PHARMACOLOGY & PHARMACY
Hatem I. Mokhtar, Noha M. Abd El-Fadeal, Mohamed A. Zayed, Eman Wahsh, Heba Kamel Badawy, Ahmed N. A. Nasr, Ahmed Al-Emam, Nermine Nosseir, Shaimaa A. Shehata, Sawsan A. Zaitone
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引用次数: 0

摘要

注意缺陷多动障碍(ADHD)是一种注意力不集中和多动的状态。神经炎症和氧化应激在ADHD的病理中是复杂的。甜菜素是一种有效的水溶性含氮抗氧化剂和抗炎分子,以前从未在多动症模型中测试过。目前的研究旨在测试甜菜素在认知和运动功能障碍方面减轻多动症小鼠的能力,以及大脑组织病理学、神经递质水平和炎症蛋白水平;分子研究得到了生物信息学调查的支持。将雄性白化小鼠分为3个实验组:(i)正常组,(ii) ADHD组,(iii) ADHD + β素50 mg/kg。我们通过在饮食中加入谷氨酸钠(SGLU)诱导ADHD 8周。采用开放场测试(OF-T)评估运动改变,大理石掩埋测试(MB-T)评估注意力和强迫行为,以及绳索爬行测试评估认知和运动功能障碍。结果ADHD对照组(SGLU喂养)的OF-T活动增加,MB-T强迫行为高。此外,ADHD对照组的脑谷氨酸水平高,多巴胺水平低,丙二醛水平高,炎症参数如toll样受体(TLRs)、肿瘤坏死因子-α (TNF-α)、核转录因子-κB (NFκB)、白细胞介素-1β (IL-1β)和il - 6水平高。相反,ADHD组的大脑Nrf2和总抗氧化剂减少。显微镜检查显示大脑有病理改变。Western blot分析和免疫染色显示ADHD组的p-53水平高于正常组。结论给药甜菜素改善了ADHD模型小鼠的大部分神经行为、生化和组织病理学结果。因此,甜菜素可以作为一种减轻儿童多动症症状的有用食物成分进行进一步的研究。图形抽象
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ameliorative effect of betanin on monosodium glutamate-induced mouse ADHD and modulation of Nrf2 and TLR4/NFκB/p53 interplay

Background

Attention-deficit hyperactivity disorder (ADHD) is a state of poor attention and hyperactivity. Neuroinflammation and oxidative stress are complicated in the pathology of ADHD. Betanin is a potent water-soluble nitrogen-containing antioxidant and anti-inflammatory molecule not tested before in ADHD models. The current study aimed to test the ability of betanin to mitigate ADHD in mice in terms of cognitive and motor dysfunction, in addition to brain histopathology, neurotransmitter levels and inflammatory protein levels; the molecular study was supported by a bioinformatic investigation. Male albino mice were allotted to three experimental groups: (i): normal, (ii): ADHD group, (iii) ADHD + betanin 50 mg/kg. We induced ADHD by including monosodium glutamate (SGLU) in the diet for 8 weeks. Cognitive and motor dysfunction were evaluated using the open field test (OF-T) for locomotor alterations, the marble burying test (MB-T) for attention and compulsive behavior, and the rope crawling test.

Results

The ADHD control group (fed with SGLU) showed increased activities in the OF-T and high compulsive behavior in the MB-T. Further, high brain glutamate and low dopamine levels were observed in the ADHD control group along with high levels of malondialdehyde and inflammatory parameters such as toll-like receptors (TLRs), tumor necrosis factor-α (TNF-α), nuclear transcription factor-κB (NFκB), interleukin-1β (IL-1β), and IL6. Conversely, brain Nrf2 and total antioxidants were reduced in the ADHD group. Microscopic investigation showed pathological alterations in the brain. Western blot analysis and immunostaining showed greater levels of p-53 in the ADHD group versus the normal group.

Conclusions

Orally administered betanin improved most neurobehavioral, biochemical, and histopathological findings in the ADHD model in mice. Hence, betanin can be considered for further investigation as a useful food component in children for mitigating ADHD symptoms.

Graphical abstract

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来源期刊
自引率
0.00%
发文量
44
审稿时长
23 weeks
期刊介绍: Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
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