Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease

Zhenguo Zhong; Zeqiang Qu; Yunping Bao; Naiping Wang; Fengfen Zhang; Wenyan Zhang

摘要：BACKGROUND: Modern pharmacological studies have demonstrated that Panax notoginseng saponins (PNS) can ameliorate and protect from neuropathological impairment. Whether PNS can improve the abnormality in memory and behavior of rats with Alzheimer’s disease (AD) remains unclear.OBJECTIVE: Based on a Morris water maze test, this study aimed to measure improvements of spatial learning and memory by PNS in a rat model of AD, and to compare effects with huperzine A.DESIGN: A completely randomized grouping design, controlled animal experiment. SETTING: Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University.MATERIALS: Ninety healthy Wistar rats of both genders, 15-month-old (n =75) and 3-month-old rats as young controls (n =15), were used for this study. The study was performed in accordance with animal ethics guidelines for the use and care of animals. PNS was provided by Weihe Pharmaceutical Co., Ltd (permission No. Z53021485, Yuxi, Yunan Province, China). Morris water maze equipment was provided by the Institute of Physiology, Chinese Academy of Science.METHODS: This study was performed at the Center of Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from June 2003 to April 2005. Of the included rats, 15 healthy aged rats were randomly chosen as aged controls, and the remaining 60 aged rats were randomly divided into 4 groups with 15 rats in each: model group, PNS high- and low-dose groups, and an huperzine A group. Rats in the model group and the 3 treated groups were treated with intraperitoneal infusion of 9.6 g/L D-galactose (5 mL/kg) every day for 6 weeks successively to induce a subacute aging model. During week 7, animals received 1 μL ibotenic acid (5 g/L) bilaterally into the nucleus basalis of Meynert to create a rat model of AD. The young and old rat controls received, in parallel, a corresponding volume of saline. Two weeks later, rats in the PNS high- and low-dose groups were gavaged with 200 and 100 mg/kg PNS suspension, respectively. Huperzine A suspension (0.3 mg/kg) was used in the huperzine A group. Rats in the other 3 groups were gavaged with a corresponding volume of normal saline. In each group, administration was carried out once per day for 4 consecutive weeks. MAIN OUTCOME MEASURES: After administration, learning and memory abilities were measured by place navigation and spatial probe tests. Recording indices consisted of escape latency (time-to-platform), number of times to find the platform within 2 minutes, number of times the animal crosses the original platform location, and the percent of swimming time in each quadrant. RESULTS: Several rats died due to inflammatory reactions following brain lesion or intragastric administration; therefore, 61 rats were included in the final analysis. Results of spatial navigation test: Escape latency of rats in the model group was significantly prolonged, and number of times to find the platform within 2 minutes were significantly reduced compared with other groups (both P < 0.05). No significant differences in these two indices were measured among the administration groups (all P > 0.05). Results of spatial probe test: Times for crossing the original platform location and percent of time spent in the quadrant of original platform location were significantly less in the model group than in the other groups (P < 0.05). There were no significant differences in these two indices among the administration groups (P > 0.05). CONCLUSION: PNS can remarkably improve spatial learning and memory abilities of rats with AD. The therapeutic effect of PNS is not dose-dependent and is equivalent to the effect of huperzine A.