Hyperphosphorylation of the microtubule-associated protein,tau,is critical to the progression of Alzheimers disease (AD).Fuzheng Quxie decoction (FQD),a Chinese herbal complex,is an effective clinical formula used to treat AD.In the current study,we employed high-performance liquid chromatography and liquid chromatography tandem mass spectrometry to identify the components of FQD.Three major components (ginsenoside Rg1,ginsenoside Re,and coptisine) were detected in the brain of FQD-fed mice,indicating their ability to cross the blood-brain barrier.To investigate the potential efficacy of FQD for treating AD,40 senescence-accelerated mice prone-8 (SAMP8) were randomly divided into model,memantine,FQD low-dose and FQD high-dose groups (3.5 and 16.5 g/kg/d,respectively).Senescence-resistant-1 mice with the same genetic background were used as controls.Drugs or distilled water were administered intragastrically once daily for 12 weeks.FQD ameliorated learning and memory deficits in SAMP8 mice on the Morris water maze,decreasing escape latency (p < 0.01) and increasing swim time within the original platform-containing quadrant (p < 0.05).Further,FQD increased the number of neurons and intraneuronal Nissl bodies in the hippocampal CA1 region.FQD also decreased the expression of phosphorylated tau protein,and increased the expression of protein phosphatase 2A (PP2A) and the N-methyl-D-aspartate receptor subunit,NR2A (p < 0.01).Our results indicate that early intervention with FQD in SAMP8 mice can improve learning and memory.Moreover,our findings suggest that the protective effect of FQD is likely mediated through an inhibition of hippocampal tau hyperphosphorylation via NMDAR/PP2A-associated proteins.