A novel traditional Chinese medicine formula restores sleep and cognitive function in APP/PS1 mice by targeting glycolytic pathways and neuroinflammatory responses

Background Alzheimer's disease (AD) is recognized as a multifactorial neurodegenerative disorder involving numerous cellular and molecular processes, such as sleep disturbance, imbalance in brain glucose metabolism and neuroinflammation; these dysregulations typically precede the onset of symptoms. Hence, the results of mono-target therapy after AD diagnosis are in many cases unsatisfactory. Objective Traditional Chinese medicine (TCM) presents significant potential for treating AD. Sleep disorders are one of the early symptoms of AD; however, there is no effective solution to sleep disorders caused by AD. Some TCMs have been shown to treat sleep disorders by regulating energy metabolism or improving neuroinflammation. This study aims to investigate if XX-F administrated in advance could alleviate AD by improving sleep quality and neuroinflammation. Methods Mice were given Xiexintongfu formula (XX-F) intragastrically for three months. Morris water maze and pentobarbital-induced sleep test were performed to evaluate cognition and sleep. Determine changes in energy metabolism related to glycolysis through western blot and specific assay kits. Using immunofluorescence and western blot to detect neuroinflammation. Results Shortened sleep duration and cognitive impairment were observed in 6-month-old APP/PS1 mice. XX-F significantly prolonged sleep duration and rescued cognition. In addition, XX-F reduced the number of amyloid-β (Aβ) plaques and ameliorated neuroinflammation, and inhibited glycolysis by reducing pyruvate kinase M2 (PKM2) and lactate levels while rescuing adenosine triphosphate (ATP) deficiency. Conclusions We demonstrate that XX-F can improve sleep and cognition of AD mice by regulating energy metabolism and reducing neuroinflammation. This is a potential treatment method for AD and requires further in-depth research.