Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, 28040-Madrid, Spain.
Life Sci. 2011 Dec 19;89(25-26):939-45. doi: 10.1016/j.lfs.2011.09.023. Epub 2011 Oct 8.
Quercetin and rutin have been reported to exert numerous pharmacological activities, such as free-radical scavenging, effects on immune and inflammatory cell functions, and could have benefits in Alzheimer's disease (AD) by mitigating cellular damage induced by reactive oxygen species (ROS). A key event in AD is the conversion of the β-amyloid (Aβ) peptide into amyloid plaques in the brain. Preventing Aβ aggregation is pursued as a therapeutic strategy for treating AD. In this study, antiamyloidogenic and antioxidant properties of quercetin and rutin were investigated.
We investigated whether quercetin and rutin affect Aβ25-35 fibrillogenesis, BACE activity and the cellular redox status.
Quercetin and rutin inhibited the formation of Aβ fibrils and disaggregated Aβ fibrils. β-secretase enzyme (BACE) activity was significantly inhibited by rutin. To resemble the in vivo Aβ-induced neurotoxicity we used a cell system overexpressing APP Swedish mutation (APPswe), which is associated with early-onset familial AD, and may promote oxidative stress due to the enhanced Aβ production. Quercetin and rutin decreased almost completely ROS generation in H(2)O(2)-treated APPswe cells. Both flavonoids increased intracellular GSH content and the redox status, and for rutin this effect was concentration dependent. Besides, quercetin and rutin diminished the index of lipid peroxidation in comparison with control APPswe cells at all concentrations tested.
Our findings may provide an explanation of the neuroprotective effect of quercetin and rutin, suggesting that they could be dietary phytochemicals able to revert the β-amyloid toxicity in vivo.
槲皮素和芦丁已被报道具有多种药理活性，如清除自由基、影响免疫和炎症细胞功能，通过减轻活性氧（ROS）引起的细胞损伤，可能对阿尔茨海默病（AD）有益。AD 的一个关键事件是β-淀粉样肽（Aβ）在大脑中转化为淀粉样斑块。防止 Aβ聚集被视为治疗 AD 的一种治疗策略。在这项研究中，研究了槲皮素和芦丁的抗淀粉样变性和抗氧化特性。
我们研究了槲皮素和芦丁是否影响 Aβ25-35 纤维形成、BACE 活性和细胞氧化还原状态。
槲皮素和芦丁抑制 Aβ纤维的形成和聚集。芦丁显著抑制β-分泌酶（BACE）活性。为了模拟体内 Aβ诱导的神经毒性，我们使用了一种过表达 APP 瑞典突变（APPswe）的细胞系统，该突变与早发性家族性 AD 相关，由于 Aβ产生增加，可能会促进氧化应激。槲皮素和芦丁几乎完全降低了 H2O2 处理的 APPswe 细胞中 ROS 的产生。两种黄酮类化合物均增加了细胞内 GSH 含量和氧化还原状态，而芦丁的这种作用呈浓度依赖性。此外，与对照 APPswe 细胞相比，槲皮素和芦丁在所有测试浓度下均降低了脂质过氧化指数。
我们的发现可能解释了槲皮素和芦丁的神经保护作用，表明它们可能是能够在体内逆转β-淀粉样毒性的膳食植物化学物质。
