Traditional Chinese medicines such as
hyperoside-rich Acanthopanax senticosus and Crataegus pinnatifida have been confirmed to exhibit anti-oxidative stress properties.
Hyperoside, the main ingredient of numerous
antioxidant herbs, may have the ability to postpone the onset of
neurodegenerative diseases. This study investigates the possible therapeutic mechanism of
hyperoside as a natural
antioxidant against
Alzheimer's disease (AD) in Caenorhabditis elegans and PC12 cells. Specifically,
hyperoside reduced
reactive oxygen species (ROS) level and Aβ42-induced neurotoxicity in C. elegans worms. Meanwhile,
hyperoside reduced ROS production and increased mitochondrial membrane potentialin Aβ42-induced PC12 cells, which possibly due to the increase of
antioxidant enzymes activity and the diminution of
malondialdehyde levels. Hoechst 33,342 staining and flow cytometry analysis results suggested that
hyperoside reverses cell apoptosis. Network pharmacology predicts potentially relevant
hyperoside targets and pathways in AD
therapy. As anticipated,
hyperoside reversed Aβ42-stimulated downregulation of the PI3K/Akt/Nrf2/HO-1. The PI3K inhibitor
LY294002 partially abolished the protective capability of
hyperoside. The results of molecular docking further indicated that the PI3K/Akt pathways may be involved in the protection of Aβ42-induced PC12 cells by
hyperoside treatment. The study provides theoretical information for research and development of
hyperoside as an
antioxidant dietary supplement.