International Journal of Molecular Sciences · 4 authors, 1 centre
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This preclinical study investigated the effects of dietary rutin and quercetin on brain oxidative stress and Alzheimer's disease (AD) markers in transgenic APPswe mice. Both flavonoids improved brain redox homeostasis (GSH/GSSG ratio) and reduced BACE1 activity and APP expression, but the study's limitation is its direct applicability to humans is uncertain as it used an animal model.
This preclinical study aimed to evaluate the neuroprotective effects of dietary quercetin and rutin, flavonoids with antioxidant properties, in a mouse model of Alzheimer's disease (AD). The study used transgenic mice expressing the human Swedish mutation APP (TgAPP), which develop early AD-like pathological features, such as elevated amyloid-β precursor protein (APP). Male and female TgAPP mice were fed a diet supplemented with quercetin or rutin for 4 weeks starting at 45 weeks of age. The primary outcome was the assessment of intracellular redox homeostasis in the brain, measured via the reduced glutathione (GSH) to oxidized glutathione (GSSG) ratio. The study also examined biomarkers of oxidative stress, APP processing, inflammation, and apoptosis. Key results showed that the TgAPP mice had a significantly depleted GSH/GSSG ratio and elevated malondialdehyde (MDA) levels compared to wild-type controls. Both quercetin and rutin diets significantly restored the GSH/GSSG ratio in the hippocampus and cortex, with effects more pronounced in males. Rutin also increased the activity of antioxidant enzymes catalase and glutathione reductase. Furthermore, both treatments significantly reduced BACE1 enzyme activity and APP gene expression. Rutin showed a trend toward increasing the non-amyloidogenic enzyme ADAM10. Treatments also reduced hippocampal caspase-3 expression and cortical IL-1β expression. The authors conclude that a diet containing rutin or quercetin, particularly rutin, may help restore redox balance and normalize APP processing in this early-stage AD mouse model. The main limitation is that this is an animal study, and the direct translational relevance to human AD progression and therapy remains to be established.
