OBJECTIVE   To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.

  METHODS   Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil (2 mg·kg^-1·d^-1) and Qishen Yizhi formula water extracts in low (1.33 g·kg^-1·d^-1) and high dose group (2.67 g·kg^-1·d^-1). The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests; HE staining was used to examine hippocampal damage in model mice; TUNEL was used to detect apoptosis of mouse hippocampal tissue; ELISA was used to detect the expression levels of oxidative stress factors and inflammatory factors in the mouse hippocampus tissue; Western blot was used to detect the expression of signaling pathway proteins related to apoptosis, oxidative stress and inflammatory stress in the hippocampus of mice.

  RESULTS   The water extract of Qishen Yizhi formula significantly shortened the latency and distance of model mice for reaching the platform in the water maze test (P < 0.01), and significantly increased the number of crossing the platform (P < 0.01); increased the exploration time and number of the Y maze new arm in model mice (P < 0.05); inhibited the TUNEL fluorescence expression in the hippocampus of model mice (P < 0.01); upregulated the activity of the oxidative stress factor superoxide dismutase (SOD) (P < 0.05) and glutathione (GSH) content (P < 0.05), and downregulated malondialdehyde (MDA) content (P < 0.05); reduced interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF-α) expression levels (P < 0.05, P < 0.01); decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3 (P < 0.05), upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1 (P < 0.05), and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB (P < 0.05).

  CONCLUSION   Qishen Yizhi formula can improve the learning and memory ability of subacute aging model mice injected with D-galactose, which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.