BACKGROUND: Leing and memory processes are accompanied by complex neuropathological and biochemical changes. Free radicals play an important role in leing and memory damage. OBJECTIVE: To observe the effects of polygonatum sibiricum polysaccharide (PSP) in comparison with vitamin E on inhibiting free radical damage, as well as improving the degree of cerebral ischemia and leing and memory in a scopolamine-induced mouse model of dementia.DESIGN: Randomized controlled animal study.SETTINGS: Department of Pharmacology, Taishan Medical College; Shandong Jewim Pharmaceutical Co., Ltd.MATERIALS: A total of 105 healthy Kunming mice, comprising 90 males and 15 females that were clean grade, were provided by the Animal Center of Taishan Medical College. PSP (extracted and purified by Huangjing, Taishan) was provided by the Department of Traditional Chinese Medicine, Taishan Medical College (purity of 79.6% by using a phenol-concentrated sulphate acid method), and hydrogen bromine acid scopolamine injection solution (SCO) by Shanghai Hefeng Pharmaceutical Co., Ltd.METHODS: This study was performed at the Pharmacological Laboratory of Taishan Medical College from March to June 2007. ① A total of 75 healthy Kunming male mice of clean grade were randomly divided into a normal control group, positive control group, and low-dosage and high-dosage PSP groups, with 15 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively. Mice in the positive control group were intragastrically administered 0.5 g/kg vitamin E. In addition, mice in both the normal control group and model group were intragastrically administered the same volume of saline, respectively, once a day for 7 consecutive days. One hour after the final administration on day 6, mice in the positive control group, model group, low-dosage and high-dosage PSP groups were subcutaneously injected with 3.0 mg/kg SCO, while mice in the normal control group were subcutaneously injected with the same volume of distilled water. Ten minutes later, the step test was employed to measure memory. The training was performed 5 times, with 30-minute intervals between 2 sets. If the mice remained on the platform (latent period) for 30 minutes, they were determined to have leed the task. An eligible percentage was then recorded. Twenty-four hours later, the number of error responses from each mouse was recorded in a 5-minute period, based on the above-mentioned parameters. Mice were sacrificed under anesthesia. The activities of glutathione hyperoxide enzyme (GSH-Px), superoxide dismutase (SOD), and the content of malondialdehyde (MDA) were assayed using an UV spectrophotometer. ② The remaining 30 healthy Kunming mice of both genders were randomly divided into 3 groups, including control group, low-dosage PSP group, and high-dosage PSP group, with 10 mice in each group. Mice in both the low-dosage and high-dosage PSP groups were intragastrically administered 0.5 g/kg and 2.0 g/kg PSP, respectively, while the mice in the control group were perfused with the same volume of saline. Forty minutes later, the mice under superficial anesthesia were decapitated, and the number and duration of mouth-opening breaths of the isolated mouse head were immediately recorded.MAIN OUTCOME MEASURE: ① Numbers of error responses within 5 minutes on the platform. ② GSH-Px and SOD activity, as well as MDA content in mouse brain tissue. ③ Numbers and duration of mouth-opening breaths of the isolated mouse head.RESULTS: Of the 105 Kunming experimental mice, two mice died due to electric shock during the step-down test, therefore, a total of 103 mice were involved in the final analysis. ① Effects of PSP on leing in mice: The eligible percentage in the high-dosage PSP group was higher than the control group at the 3rd and 5th training sessions (P < 0.05). ② Effects of PSP on memory in mice: The number of errors in the step-down test in the model group was higher than in the normal control group (P < 0.01). Compared to the model group, the number of errors in the step-down test was lower in both the low-dosage and high-dosage PSP groups (P < 0.01). ③ Effects of PSP on amount of GSH-Px, SOD, and MDA in mouse brain tissue: SOD and GSH-Px activity was higher in both the low-dosage and high-dosage PSP groups than in the model group. MDA content was lower in the high-dosage PSP group, compared to the model group. GSH-Px activity in the brain tissue of the high-dosage PSP group was similar to the positive control group (P > 0.05). ④ Effects of PSP on acute cerebral ischemia in mice: The low-dosage PSP, and in particular the high-dosage PSP, prolonged the number and duration of mouth-opening breaths of the isolated mouse head (P < 0.05, 0.01).CONCLUSION: PSP can improve leing and memory in a scopolamine-induced mouse model of dementia by reducing the damaging effects of cerebral ischemia and anti-oxidation. In addition, the effects are dose-dependent and are similar to those provided by vitamin E.