Objective: To study the mechanism of Dihuang Yinzi on the activation of energy metabolism disorder-induced endoplasmic reticulum stress (ERS) activating transcription factor4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway in APP/PS1 transgenic mice

and investigate its mechanism on neuronal apoptosis. Method: The 120 APP/PS1 transgenic mice at 4-month-old were randomly divided into normal control group

model group

positive drug (Aricept

1 mg·kg-1) group

and low-dose

middle-dose

and high-dose groups of Dihuang Yinzi (1.25

2.5

5 g·kg-1). Except for the normal control group

the other groups were intraperitoneally injected with 3-nitropropionic acid (3-NP) at a dose of 100 mg·kg-1 to establish models. The mice in normal control group were injected intraperitoneally with an equal volume of normal saline. Dihuang Yinzi and Aricept were given by oral administration for 1 week. Then Real-time PCR was used to detect ATF4

CHOP mRNA levels in mouse brain. The protein expression levels of glucose-regulated protein 78(GRP78)

ATF4

CHOP

B-cell lymphoma-2 (Bcl-2)

and Bcl-2-associated X protein (Bax) in brain tissue of mice were detected by Western blot. Terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) staining was used to evaluate the neuronal apoptosis in mouse brain and the apoptosis rate. Result: As compared with the normal group

3-NP-induced energy metabolism disorder significantly increased the expression of ERS marker protein GRP78 (P<0.01)

increased ATF4 and CHOP mRNA levels (P<0.01) and protein expression (P<0.01)

down-regulated anti-apoptosis protein Bcl-2 (P<0.01) and up-regulated of pro-apoptotic protein Bax (P<0.01)

and promoted the rate of neuronal apoptosis in the brain of model mice. As compared with the model group

Dihuang Yinzi could significantly reduce the mRNA and protein expression of GRP78 (P<0.05

P<0.01)

ATF4 and CHOP (P<0.05

P<0.01)

up-regulate anti-apoptotic protein Bcl-2 (P<0.05

P<0.01)

down-regulate pro-apoptotic protein Bax (P<0.05

P<0.01)

and reduce neuronal apoptosis in brain tissue. TUNEL results showed that Dihuang Yinzi can significantly reduce the neuronal apoptosis rate in mouse brain.