Arctigenin attenuated spatial memory impairment in pR5 mice by regulating mitochondrial energy metabolism

Arctigenin (ATG) is a natural product with a variety of biological activity, which can improve the pathological changes of Alzheimer's disease (AD) model mice through multiple mechanisms. This study aims to further elucidate the potential mechanism by which ATG improves memory impairment in AD mice.Here, we used pR5 mice as an experimental model, and ATG was administered continuously for 90 days. Novel object recognition, Y-maze, and Morris water maze were used to evaluate the therapeutic effect of ATG on memory impairment in AD mice. Immunohistochemical and immunofluorescence analyses were used to evaluate the effects of ATG on tau hyperphosphorylation and neuroinflammation, respectively. Finally, proteomics techniques were used to explore the possible mechanism of ATG.ATG significantly improved memory impairment in pR5 mice and inhibited tau phosphorylation in the hippocampus and neuroinflammation in the cortex. According to the proteomic analysis, the altered cognitive function of ATG was associated with the proteins of the tricarboxylic acid cycle and the electron transport chain.These results suggest that ATG is a potential therapeutic agent for diseases related to aberrant energy metabolism that can treat AD by improving mitochondrial function.