| 1 | Effect of Panax notoginseng saponins on the expression of beta-amyloid protein in the cortex of the parietal lobe and hippocampus, and spatial learning and memory in a mouse model of senile dementia显示文摘BACKGROUND: The pharmacological actions of Panax notoginseng saponins (PNS) lie in removing free radicals, anti-inflammation and anti-oxygenation. It can also improve memory and behavior in rat models of Alzheimer’s disease. OBJECTIVE: Using the Morris water maze, immunohistochemistry, real-time PCR and RT-PCR, this study aimed to measure improvement in spatial learning, memory, expression of amyloid precursor protein (App) and β-amyloid (Aβ), to investigate the mechanism of action of PNS in the treatment of AD in the senescence accelerated mouse-prone 8 (SAMP8) and compare the effects with huperzine A. DESIGN, TIME AND SETTING: A completely randomized grouping design, controlled animal experiment was performed in the Center for Research & Development of New Drugs, Guangxi Traditional Chinese Medical University from July 2005 to April 2007. MATERIALS: Sixty male SAMP8 mice, aged 3 months, purchased from Tianjin Chinese Traditional Medical University of China, were divided into four groups: PNS high-dosage group, PNS low-dosage group, huperzine A group and control group. PNS was provided by Weihe Pharmaceutical Co., Ltd. (batch No.: Z53021485, Yuxi, Yunan Province, China). Huperzine A was provided by Zhenyuan Pharmaceutical Co., Ltd. (batch No.: 20040801, Zhejiang, China). METHODS: The high-dosage group and low-dosage group were treated with 93.50 and 23.38 mg/kg PNS respectively per day and the huperzine A group was treated with 0.038 6 mg/kg huperzine A per day, all by intragastric administration, for 8 consecutive weeks. The same volume of double distilled water was given to the control group. MAIN OUTCOME MEASURES: After drug administration, learning and memory abilities were assessed by place navigation and spatial probe tests. The recording indices consisted of escape latency (time-to-platform), and the percentage of swimming time spent in each quadrant. The number of Aβ1-40, Aβ1-42 and App immunopositive neurons in the brains of SAMP8 mice was analyzed by immunohistochemistry. The mRNA content of App, tau, acetylcholinesterase, and synaptophysin (Syp) was tested by real time PCR and RT-PCR. RESULTS: The PCR results show that PNS can downregulate the expression of the App gene and upregulate the expression of the Syp gene in the parietal cortex and hippocampus of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than those of the PNS low-dosage group and the huperzine A group (P < 0.05). The results of the Morris water maze and immunohistochemistry indicated that PNS can improve the capacity for spatial learning and memory in SAMP8 mice, and reduce the content of Aβ1-40, Aβ1-42 and expression of App in the brains of SAMP8 mice. The therapeutic effects of the PNS high-dosage group were greater than that of the PNS low-dosage group and the huperzine A group (P < 0.05). CONCLUSION: These results support the hypothesis that PNS plays a therapeutic and protective role on the pathological lesions and learning dysfunction of Alzheimer’s disease. The therapeutic effects of PNS for Alzheimer’s disease are possibly achieved through downregulating the expression of the App gene and upregulating the expression of the Syp gene. The therapeutic effects of PNS are dose-dependent and are greater than the effect of huperzine A. | Zhenguo Zhong Dengpan Wu Liang Lu Jinsheng Wang Wenyan Zhang Zeqiang Qu | 2008 | Neural Regeneration Research2008，3，12： | 9 |
| 2 | Effects of Panax notoginseng saponins in a rat model of Alzheimer's disease显示文摘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. | Zhenguo Zhong Zeqiang Qu Yunping Bao Naiping Wang Fengfen Zhang Wenyan Zhang | 2008 | Neural Regeneration Research2008，3，1： | 5 |
您所在的机构暂未开通此部分的功能，请联系管理员