Poria cocos could ameliorate cognitive dysfunction in APP/PS1 mice by restoring imbalance of Aβ production and clearance and gut microbiota dysbiosis.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Amyloid beta-protein (Aβ) plaques, which are the hallmark of AD, are formed from the imbalance of Aβ production and clearance accompanied by neuroinflammation, gut dysbiosis, and metabolite dysfunction. All of these processes give rise to neurochemical deficiencies and synaptic dysfunction, which ultimately contribute to recognition dysfunction. Poria cocos (PC), which contains multiple active ingredients, plays a significant role in the treatment of multiple-pathogenesis senile diseases such as AD. Nevertheless, there are only very few investigations on the intricate action mechanism of PC for the treatment of AD. In this study, we evaluate the multi-target cure effect of PC on APP/PS1 mice by behavioral, immunohistochemical (IHC), targeted metabolomics, and 16S rRNA sequencing experiments. Mice treated with PC showed significant improvements in cognitive function as evaluated by the behavioral experiment. IHC revealed that PC treatment relieved Aβ deposition by reducing the formation of Aβ and increasing its clearance. Moreover, PC treatment improved gut dysbiosis, which reversed the metabolite dysfunction of bile acid. These findings reveal that PC is a promising therapeutic agent, which might ameliorate the cognitive function of AD by restoring the imbalance of Aβ production and clearance and gut microbiota dysbiosis.