Orientin Improves Cognition by Enhancing Autophagosome Clearance in an Alzheimer's Mouse Model

Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the presence of β-amyloid (Aβ) plaques and defective autophagy in the brain, which is believed to cause neuronal dysfunction. By using APP/PS1 transgenic AD mice, we investigated the influence of orientin (Ori) on cognitive function and its underlying mechanisms in AD models. Our data indicated that Ori improved spatial learning and memory in APP/PS1 mice, possibly through decreasing brain Aβ deposition and attenuating autophagy impairment. Ori decreased the LC3-II/I ratio, p62 and cathepsin D (Ctsd) protein levels and the number of autolysosomes, whereas the protein levels of Ulk1 and Beclin-1 were no different between the control and treatment groups, indicating increased autolysosome clearance and thus a decreased Aβ burden in the brain. Our results showed that Ori could enhance autolysosome clearance, decrease brain Aβ deposition and improve learning and memory in AD mice.