Long-term oral administration of hyperoside ameliorates AD-related neuropathology and improves cognitive impairment in APP/PS1 transgenic mice

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by the pathological hallmarks of beta-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Hyperoside, a flavone glycoside isolated from Rhododendron brachycarpum G. Don (Ericaceae), has neuroprotective effects against A beta both in vitro and in vivo. However, whether hyperoside could delay AD pathogenesis remains unclear. In the present study, we observed if chronic treatment with hyperoside can reverse pathological progressions of AD in the APP/PS1 transgenic mouse model. Meanwhile, we attempted to elucidate the molecular mechanisms involved in regulating its effects. After 9 months of treatment, we found that hyperoside can improve spatial learning and memory in APP/PS1 transgenic mice, reduce amyloid plaque deposition and tau phosphorylation, decrease the number of activated microglia and astrocytes, and attenuate neuroinflammation and oxidative stress in the brain of APP/PS1 mice. These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3 beta levels. Hyperoside confers neuroprotection against the pathology of AD in APP/PS1 mouse model and is emerging as a promising therapeutic candidate drug for AD.

Automated summary

Hyperoside improves spatial learning and memory, reduces amyloid plaque deposition and tau phosphorylation, decreases the number of activated microglia and astrocytes, and attenuates neuroinflammation and oxidative stress in APP/PS1 transgenic mice. These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3 beta levels, suggesting hyperoside as a promising therapeutic candidate drug for Alzheimer's disease.