Quercetin and rutin exhibit antiamyloidogenic and fibril-disaggregating effects in vitro and potent antioxidant activity in APPswe cells

Karim Jiménez-Aliaga, Paloma Bermejo-Bescós, Juana Benedí, Sagrario Martín-Aragón
Life Sciences 2011 December 19, 89 (25-26): 939-45

AIMS: 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.

MAIN METHODS: We investigated whether quercetin and rutin affect Aβ25-35 fibrillogenesis, BACE activity and the cellular redox status.

KEY FINDINGS: 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.

SIGNIFICANCE: 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.

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