Kaempferol-Conjugated Manganese Oxide Nanocomposites Mitigate Aluminium Chloride-Induced Neurobehavioral Impairments in a Rat Model of Alzheimer’s disease

IF 2.4 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Heng Yu, Xiufeng Liu, Juan Liu, Dong Tang
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引用次数: 0

Abstract

The neurodegenerative illness Alzheimer’s disease (AD) causes cognitive decline. The production of oxidative stress in neurons is thought to play a role in the emergence of AD. The antioxidants, including kaempferol, reduce the course of AD; however, their use is limited by poor bioavailability. Kaempferol-conjugated manganese oxide nanocomposites (KMF@PEG-MnO2 NCs) exhibit enhanced protective effects against AD compared to free kaempferol. In this study, the potential of KMF@PEG-MnO2 NCs as an anti-Alzheimer’s disease (AD) agent was explored through in silico and experimental approaches. The effective preparation of KMF@PEG-MnO2 NCs was validated by FT-IR, XRD, DLS, and SEM-EDX characterization techniques. The influence of KMF@PEG-MnO2 NCs on antioxidant capacity using the DPPH assay, reactive oxygen species (ROS) quantification with the SH-SY5Y cell line, and determining the amyloid β disaggregation was determined. Additionally, blood-brain barrier permeability was assessed with brain endothelial cells, and an anticholinesterase study was performed to explore its potential for treating Alzheimer’s disease. Surface characterization revealed a spherical shape of the nanoparticle. DPPH and FR assay showed a substantial rise in antioxidant defence for KMF@PEG-MnO2 NCs compared to KMF. Anti-aggregation studies demonstrated the nanoparticle’s ability to inhibit Aβ fibrils. Additionally, the BBB permeability assay indicated that the nanoparticle can permeate the BBB. Furthermore, in vivo studies demonstrated that KMF@PEG-MnO2 NCs protected against cognitive and synaptic deficits in AlCl3-induced AD rats (AlCl₃-AD). KMF@PEG-MnO2 NCs significantly reduced AChE activity. Furthermore, it markedly reduced the brain’s levels of nitric oxide (NO) while increasing the function of superoxide dismutase (SOD) and catalase (CAT) activities. Overall, the findings suggest that KMF@PEG-MnO2 NCs may serve as a promising therapeutic candidate for AD management.

山奈酚共轭氧化锰纳米复合材料减轻氯化铝诱导的阿尔茨海默病大鼠模型的神经行为损伤。
神经退行性疾病阿尔茨海默病(AD)会导致认知能力下降。神经元氧化应激的产生被认为在阿尔茨海默病的出现中起作用。山奈酚等抗氧化剂可减少AD病程;然而,由于生物利用度差,它们的使用受到限制。与游离山奈酚相比,山奈酚共轭氧化锰纳米复合材料(KMF@PEG-MnO2 NCs)对AD的保护作用增强。在这项研究中,KMF@PEG-MnO2 NCs作为一种抗阿尔茨海默病(AD)药物的潜力通过硅和实验方法进行了探索。通过FT-IR, XRD, DLS和SEM-EDX表征技术验证了KMF@PEG-MnO2纳米碳纳米管的有效制备。采用DPPH法、SH-SY5Y细胞系活性氧(ROS)定量法和β淀粉样蛋白分解法测定KMF@PEG-MnO2 NCs对抗氧化能力的影响。此外,用脑内皮细胞评估血脑屏障通透性,并进行抗胆碱酯酶研究以探索其治疗阿尔茨海默病的潜力。表面表征显示纳米颗粒呈球形。DPPH和FR分析显示,与KMF相比,KMF@PEG-MnO2 NCs的抗氧化防御能力显著提高。抗聚集研究证明了纳米颗粒抑制β原纤维的能力。此外,血脑屏障通透性试验表明,纳米颗粒可以渗透血脑屏障。此外,体内研究表明KMF@PEG-MnO2 NCs可以防止alcl3诱导的AD大鼠(AlCl₃-AD)的认知和突触缺陷。KMF@PEG-MnO2 nc显著降低AChE活性。此外,它显著降低了大脑的一氧化氮(NO)水平,同时增加了超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性。总的来说,研究结果表明KMF@PEG-MnO2 NCs可能作为一种有希望的AD治疗候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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