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用于预防阿尔茨海默病的膳食补充剂:以及分子对接研究

Dietary supplements for prevention of Alzheimer's disease: and molecular docking studies.

作者信息

Mohamed Doha Abdou, Mohamed Rasha Salah, Fouda Karem, Mabrok Hoda Bakr

机构信息

Nutrition and Food Science Department, Food Industries and Nutrition Institute, National Research Centre, Dokki 12622, Cairo, Egypt.

出版信息

Iran J Basic Med Sci. 2025;28(2):170-180. doi: 10.22038/ijbms.2024.79960.17320.

Abstract

OBJECTIVES

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in people over 65. The present research aimed to investigate the potential of different dietary supplements (DS) in preventing AD in an experimental animal model and study.

MATERIALS AND METHODS

Three DS containing a mixture of wheat-germ oil and black pepper extract/or turmeric extract were prepared. Total phenolic content, HPLC-phenolic profile, phytosterols content, fatty-acids profile, and anti-oxidant activity were evaluated in all DS. The protective effect of the prepared DS was assessed through their impact on cholinergic neurotransmission and the gene expression of GSK3β, APP, and Akt. Oxidative stress and inflammatory markers were evaluated. The inhibition activities against acetylcholinesterase (AChE) and reduction of amyloid-β aggregation of the major phytochemicals present in the studied DS were evaluated using molecular docking study.

RESULTS

Molecular docking revealed that rosmarinic acid and β-Sitosterol exhibited the strongest binding affinities for AChE and Amyloid-β, respectively. The results showed that all DS reduced cholinergic neurotransmission, decreased TNF-α as an inflammatory marker, and improved oxidative stress status. All DS down-regulated the expression of GSK3β and APP while significantly up-regulating the expression of the Akt gene.

CONCLUSION

The present study concluded that all DS enhanced cholinergic neurotransmission, reduced inflammation, and improved oxidative stress status by impacting the expression of GSK3β, Akt, and APP genes. Rosmarinic acid and β-sitosterol showed promising effects for treating AD, according to an molecular docking study. The studied dietary supplements were considered promising candidates for the prevention of AD.

摘要

目的

阿尔茨海默病(AD)是65岁以上人群中最常见的神经退行性疾病之一。本研究旨在探讨不同膳食补充剂(DS)在实验动物模型中预防AD的潜力并进行研究。

材料与方法

制备了三种含有小麦胚芽油与黑胡椒提取物/姜黄提取物混合物的DS。对所有DS评估了总酚含量、高效液相色谱-酚类图谱、植物甾醇含量、脂肪酸图谱和抗氧化活性。通过所制备的DS对胆碱能神经传递以及糖原合成酶激酶3β(GSK3β)、淀粉样前体蛋白(APP)和蛋白激酶B(Akt)基因表达的影响来评估其保护作用。评估了氧化应激和炎症标志物。使用分子对接研究评估了所研究的DS中主要植物化学物质对乙酰胆碱酯酶(AChE)的抑制活性以及对淀粉样β蛋白聚集的减少作用。

结果

分子对接显示迷迭香酸和β-谷甾醇分别对AChE和淀粉样β蛋白表现出最强的结合亲和力。结果表明,所有DS均降低了胆碱能神经传递,降低了作为炎症标志物的肿瘤坏死因子-α(TNF-α),并改善了氧化应激状态。所有DS均下调了GSK3β和APP的表达,同时显著上调了Akt基因的表达。

结论

本研究得出结论,所有DS通过影响GSK3β、Akt和APP基因的表达来增强胆碱能神经传递、减轻炎症并改善氧化应激状态。根据分子对接研究,迷迭香酸和β-谷甾醇对治疗AD显示出有前景的效果。所研究的膳食补充剂被认为是预防AD的有前景的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df0/11756737/d82dece4217a/ijbms-28-170-g001.jpg

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