Objective: To explore the effect and mechanism of Dihuang Yinzi on β-amyloid protein (Aβ) accumulation via protein kinase r-like endoplasmic reticulum kinase (PERK)

eukaryotic initiation factor 2α (eIF2α) pathway in energy inhibited APP/PS1 transgenic Alzheimer's disease (AD) mice. Method: APP/PS1 transgenic mice at 4-month-old were randomly divided into normal control group

model group

positive drug group (Aricept)

Dihuang Yinzi low-

medium-and high-dose groups. Mice were intraperitoneally injected with 100 mg·kg-1 3-nitropropionic acid (3-NP) except those in normal control group (intraperitoneally injected with normal saline) to establish models. Drug administration was given immediately modeling

and after 1 week of intragastric administration

the learning and memory ability of mice was tested by Morris water maze test; the contents of adenosine triphosphate (ATP)

adenosine diphosphate (ADP)

and adenosine monophosphate (AMP) in the brain of mice were detected by high performance liquid chromatography (HPLC); and the energy charge (EC) was calculated.Western blot was performed to detect the levels of PERK

eIF2α phosphorylation and β-amyloid precursor protein hydrolase 1 (BACE1) expression in the brain of mice. The transcriptional level of BACE1 gene was detected by Real-time fluorescence quantitative polymerase chain reaction(PCR). The content of cerebral Aβ was detected by enzyme-linked immunosorbent assay (ELISA). Result: Morris water maze test showed that as compared with the normal group

Dihuang Yinzi can significantly shorten the escape latency of model mice in navigation test (P<0.05

P<0.01). In spatial probe test

Dihuang Yinzi can increase the number passing the target area (P<0.05

P<0.01) and the residence time in target quadrant (P<0.01)

reduce the residence time in opposite quadrant (P<0.05

P<0.01). Dihuang Yinzi can significantly decrease AMP level

increase ATP and ADP levels

and significantly improve the cerebral EC level (P<0.05

P<0.01)

inhibit the phosphorylation of PERK and eIF2α (P<0.01)

decrease the protein level of BACE1 (P<0.01)

but had no significant effect on BACE1 gene transcription. Besides

Dihuang Yinzi can reduce the cerebral Aβ content in model mice (P<0.01). Conclusion: Dihuang Yinzi could prevent energy metabolism disturbance-induced endoplasmic reticulum stress via inhibiting PERK/eIF2α activation

reduce cerebral Aβ accumulation

and improve cognition in 3-NP induced energy inhibited APP/PS1 mice.