Abstract: Objective To investigate the effect and mechanism of Gynostemma pentaphyllum Makino(GPM)on learning and memory ability in dementia mice.Methods We reproduced the model of mice with senile dementia of the Alzheimer type(SDAT)using D-galactose combined with sodium nitrite and aluminum muriate and then divided the model mice randomly into 6 groups:a control group,a model group,three groups of GPM at dosages of 50,150,and 250 mg/kg,and a donepezil group (positive control).After continuous treatments for 3 months,the learning and memory ability of the mice was assessed with water maze test and the contents of antioxidants and β-amyloid precursor protein(APP)in brain of the mice were detected with reagent kit method.Results Compared with those of the control group,the latency (18.76±2.32 s) of and the time (15.27±1.42 s) crossing the platform for the first time of the model mice prolonged,while the time of activity in original platform (6.08±1.17 s) shortened.Compared with those of the model group,the latency (7.58±1.93 s) of and the time (8.17±0.68 s) crossing the platform for the first time of the mice treated with 250 mg/kg GPM decreased obviously but the time of activity in original platform (12.55±2.07 s) lengthened.Compared with those of the control group,the activity of superoxide dismutase (SOD)(200.91±28.28 U/mg) and glutathione peroxidase (GSH-Px)(3.89±0.71 U/mg) in brain tissues of the model mice decreased significantly,and the level of malondialdehyde (MDA)(6.51±0.63 nmol/mg) increased.Compared with those of the model group,the activity of SOD (305.97±98.65 U/mg) and GSH-Px (11.62±2.52 U/mg) in brain tissues of the mice treated with 250 mg/kg GPM increased significantly,and the level of MDA (2.29±0.95 nmol/mg) decreased,with significant differences (P<0.01 for all).Compared with those of the control group,the expression of α secretase form of soluble amyloid precursor protein (sAPPα)(1.869±0.12 ng/g) in brain tissues of the model mice decreased and the expression of amyloid-beta-42 (Aβ₄₂)(6.668±0.647μg/g) increased.Compared with that of the model group,the sAPPα (2.097±0.11 ng/g) increased but Aβ₄₂ (5.812±0.632μg/g) decreased in brain tissues of the mice treated with GPM,with significant differences (both P<0.01).Conclusion Gynosaponin can improve cognitive ability in dementia mice and its mechanism may be related to the reduced antioxidant damage and Aβ expression in brain tissues.