黄酮醇在阿尔茨海默病中的治疗潜力:抑制淀粉样蛋白-β、氧化应激和神经炎症

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2025-09-03 DOI:10.1002/biof.70047
Mohammad Yasin Zamanian, Lusine G. Khachatryan, Mahzad Heidari, Razieh Darabi, Maryam Golmohammadi, Raed Fanoukh Aboqader Al-Aouadi, Esra Küpeli Akkol
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种以淀粉样蛋白-β (a β)聚集、氧化应激和神经炎症为特征的进行性神经退行性疾病,仍然是一个重大的全球健康挑战。本研究探讨了黄酮醇——槲皮素、山奈酚、杨梅素和非司汀——通过不同的分子机制靶向Aβ聚集并减轻AD病理的治疗潜力。我们的研究结果表明,黄酮醇可以有效抑制Aβ寡聚和纤维的形成,通过Nrf2/HO-1通路激活减少氧化应激,并通过调节小胶质细胞极化抑制神经炎症。此外,这些化合物增强线粒体功能,促进自噬介导的Aβ聚集体清除,并调节β-分泌酶(BACE1)和α-分泌酶(ADAM10/17)等关键酶,有利于非淀粉样蛋白生成途径。槲皮素通过激活TrkB信号,减少tau磷酸化和增强突触可塑性来显示神经保护作用。山奈酚通过ER/ERK/MAPK途径阻止a β诱导的细胞凋亡,抑制乙酰胆碱酯酶活性,改善认知结果。杨梅素通过GSK3β/ERK2信号调节改善线粒体功能障碍和氧化损伤,并通过纳米结构脂质载体传递时显示出更高的脑生物利用度。非西汀通过上调神经蛋白酶表达,抑制神经炎症,并通过恢复突触蛋白水平改善突触功能,从而减轻Aβ负担。总的来说,黄酮醇通过解决其复杂的发病机制,显示出针对AD的多靶点治疗潜力。它们跨越血脑屏障的能力和低毒性特征使它们成为进一步临床开发的有希望的候选者。这项研究强调了黄酮醇作为阿尔茨海默病治疗的天然药物的潜力,并强调了它们在推进多机制治疗策略中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Therapeutic Potential of Flavonols in Alzheimer's Disease: Inhibiting Amyloid-β, Oxidative Stress, and Neuroinflammation

The Therapeutic Potential of Flavonols in Alzheimer's Disease: Inhibiting Amyloid-β, Oxidative Stress, and Neuroinflammation

The Therapeutic Potential of Flavonols in Alzheimer's Disease: Inhibiting Amyloid-β, Oxidative Stress, and Neuroinflammation

Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) aggregation, oxidative stress, and neuroinflammation, remains a significant global health challenge. This study investigates the therapeutic potential of flavonols—quercetin, kaempferol, myricetin, and fisetin—in targeting Aβ aggregation and mitigating AD pathology through diverse molecular mechanisms. Our findings reveal that flavonols effectively inhibit Aβ oligomerization and fibril formation, reduce oxidative stress via Nrf2/HO-1 pathway activation, and suppress neuroinflammation by modulating microglial polarization. Additionally, these compounds enhance mitochondrial function, promote autophagy-mediated clearance of Aβ aggregates, and regulate key enzymes such as β-secretase (BACE1) and α-secretases (ADAM10/17), favoring non-amyloidogenic pathways. Quercetin demonstrated neuroprotective effects by activating TrkB signaling, reducing tau phosphorylation, and enhancing synaptic plasticity. Kaempferol prevented Aβ-induced apoptosis via the ER/ERK/MAPK pathway and inhibited acetylcholinesterase activity, improving cognitive outcomes. Myricetin ameliorated mitochondrial dysfunction and oxidative damage through GSK3β/ERK2 signaling modulation and showed enhanced brain bioavailability when delivered via nanostructured lipid carriers. Fisetin reduced Aβ burden by upregulating neprilysin expression, suppressed neuroinflammation, and improved synaptic function by restoring synaptic protein levels. Overall, flavonols exhibit multi-targeted therapeutic potential against AD by addressing its complex pathogenesis. Their ability to cross the blood–brain barrier and low toxicity profiles position them as promising candidates for further clinical development. This study underscores the potential of flavonols as natural agents for AD treatment and highlights their role in advancing multi-mechanistic therapeutic strategies.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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