Objective To investigate the effect of chronic stress on rat behavior changes,and specific protein neurogranin (Ng) level changes to explore the control efficiency ofginsenoside Rgl in cognitive impairment.Methods Thirty-six adult male SD rats were randomly divided into control group,model group (chronic unpredictable stress animal models,CUS),and CUS-G treatment group.The chronic stress models in the later two groups were established by CUS;rats in the CUS-G treatment group were given 11 00 mg/kg ginsenoside Rgl;Behavior changes of rats were detected by sugar consumption test and body weight measuring.Morris water maze test was used to study the learning and memory abilities.The Ng content in the cortex and hippocampus was detected by Western blotting.The Ng expression in the cortex and hippocampus was measured by immumohistochemical staining.Morphological changes in the target areas of animal models were detected by HE staining.Results As compared with the control group and CUS-G treatment group,the CUS model group had significantly decreased sugar consumption and weight (P＜0.05).The water maze test showed that learning and memory abilities in rats decreased significantly after chronic stress,and the escape latency in the CUS-G treatment group was reduced,which showed significant difference as compared with that in the control group and CUS model group (P＜0.05).As compared with the control group,the CUS model group had significantly decreased Ng content in the cerebral cortex and hippocampus and average absorbance values of Ng (P＜0.05),while the CUS-G treatment group had significantly increased Ng content in the cerebral cortex and hippocampus and average absorbance values of Ng as compared with the CUS model group (P＜0.05).Conclusions Ginsensode Rg1 (100 mg/kg) can increase the level of Ng in the cerebral cortex and hippocampus to restore the damage of cognitive ability.