Effects of ginsenoside of stem and leaf combined with choline on learning and memory ability of rat models with Alzheimer diseases

Xiaomin Zhao; Xianglin Xie; Zuoli Xia; Yunsheng Gao; Yuyun Zhu; Hongxia Gu

摘要：BACKGROUND: Central adrenergic nerve and 5-serotonergic nerve can influence central cholinergic nerve on learning and memory and make easy for study; however, ginsenoside of stem and leaf (GSL) can improve functions of central adrenergic nerve; moreover, 5-serotonergic nerve and the combination with choline can produce synergistic effect and enhance learning and memory ability so as to improve learning and memory disorder of patients with Alzheimer disease (AD).OBJECTIVE: To observe the effects of GSL combining with choline on learning and memory of AD model rats.DESIGN: Randomized grouping design and controlled animal study.SETTING: Department of Pharmacology, Taishan Medical College.MATERIALS: The experiment was carried out in the Pharmacological Department of Medical College of Jilin University from October 1996 to January 1997. Forty healthy male Wistar rats of clean grade were randomly divided into 5 groups, including sham-injury group, model group, GSL group, choline group and combination group, with 8 rats in each group. Main medications: GSL with the volume more than 92.8% was provided by Department of Chemistry, Norman Bethune Medical College of Jilin University. Panaxatriol, the main component, was detected with thin layer scanning technique and regarded as the index of GSL quality [(55±1)%, CV= 2%, n= 5]. Choline was provided by the Third Shanghai Laboratory Factory.METHODS: 150 nmol quinolinic acid was used to damage bilateral Meynert basal nuclei of adult rats so as to establish AD models. Rats in GSL, choline and combination groups were intragastric administrated with 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days 400 mg/kg GSL, 200 mg/kg choline (20 mL/kg), and both respectively last for 17 days starting from two days before operation. Rats in sham-injury group and model group were perfused with the same volume of distilled jumped up safe platform when they were shocked with 36 V alternating current. If rats jumped down from the platform and the feet touched railings, the response was wrong. Numbers of wrong response were recorded within 3 minutes, and then the test was redone after 24 hours. ② Morris water-maze spatial localization task:Swimming from jumping-off to platform directly was regarded as right response. Additionally, 4 successively right responses were regarded as the standard. Each rat was trained 10 times a day with 120 s per time for 3successive days. The interval was 30 s. Three days later, numbers of right response were recorded. The traincortex: Rats were sacrificed at 17 days after operation to obtain cerebral cortex to measure activity of choilne acetylase with radiochemistry technique. ④ Synergistic effect: It was expressed as Q value: Q value = factual incorporative effect/anticipant incorporative effect; Q ≥ 1 was regarded as synergistic effect. Anticipant incorporative effect = (EA+EB-EA· EB), EA and EB were single timing effect, respectively in GSL group and choline group. E(step-down test and Morris water maze test) = (x in model group - factual value in medicine groups)/x in model group; E (activity of choiine acetylase) = (factual value in medicine groups -xin model group)/x in model group.MATN OUTCOME MEASURES : ① Passive avoidance step-down test and Morris water-maze spatial localization task in the study of learning and memory; ② activity of choiine acetylase.RESULTS: All 40 rats were involved in the final analysis. ① Passive avoidance response: At learning phase on first day and retesting phase on the next day, numbers of wrong responses within 3 minutes were more in model group than sham operation group, and there was significant difference [(5.88±1.46), (2.25±0.87) times;(2.63±1.06), (0.50±0.53) times; P＜ 0.01]; numbers of wrong responses within 3 minutes were less in combination group than model group, and there was significant difference [learning phase: (1.12±0.83), (5.88±1.46)times; retesting phase: (0.38±0.74), (2.63±1.06) times, P ＜ 0.01]; moreover, effect was stronger than that inGSL group and choline group. The Q value was 1.07 and 1.59, respectively and it showed synergistic effect. ② Spatial localization task: Training times were more in model group than sham operation group, and there was significant difference [(2.9±2.5), (12.6±3.5) times; P ＜ 0.01]. Training times were less in combination group than model group, and there was significant difference [(11.8±2.4), (27.9±2.5) times, P ＜ 0.01]; moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.07 and it showed synergistic effect. ③ Activity of choilne acetylase: Activity was lower in model group than sham operation group, and there was significant difference [(30.56±8.33), (61.11 ±8.33) nkat/g; P ＜ 0.01]. Activity was higher in combination group than model group and there was significant difference [(50.00±8.33), (30.56±8.33) nkat/g, P ＜ 0.01];moreover, effect was stronger than that in GSL group and choline group. The Q value was 1.5 and it showed synergistic effect.CONCLUSION: GSL in combination with choline can synergically improve the disorder of learning and memory of AD model rats. Its mechanism may be involved in enhancing the function of central cholinergic system.