2,2′,4′‐Trihydroxychalcone from Glycyrrhiza glabra as a new specific BACE1 inhibitor efficiently ameliorates memory impairment in mice

摘要: Alzheimer's disease (AD) characterizes a progressive neurodegenerative disorder of the brain, while AD patients are afflicted with irreversible loss neurons and further intellectual abilities including memory reasoning. One typical hallmarks is deposition senile plaque that contributed mainly by amyloid-beta (Abeta), whose production initiated beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1). Inhibition BACE1 thereby regarded as an attractive strategy for anti-AD drug discovery. Here, we reported natural product 2,2',4'-trihydroxychalcone (TDC) from Glycyrrhiza glabra functioned specific non-competitive inhibitor against enzyme, potently repressed beta-cleavage APP Abeta in human embryo kidney cells-APPswe cells. Moreover, amelioration ability this compound vivo impairment was evaluated APP-PS1 double transgenic mice model. It discovered treatment 9 mg/kg/day TDC could obviously decrease formation, efficiently improve based on Morris water maze test. Our findings thus demonstrated new ameliorate mice, expected to be potentially used lead reagent development.