| 1.ObjectivePanax notoginseng and Geniposide are the main components of TongLuoJiuNao which is an classic traditional Chinese medicine prescription treating on Ischemic stroke. It is proved to improve the learning and memory abilities on Stroke patients. Based on these facts, our group designed to study the the mechanism of their therapy effective, our studies indicated that the compatibility of Panax notoginseng and Geniposode has the protective abilities to nerves and blood vessel. Besides, the number of neurons in the hippocampus increased and the synaptic vesicle expressed more synaptophysin with the improvement of neural plasticity after being conducted with these two drugs. But the treatment of Panax notoginseng and Geniposide on APP/PS1mice was not clear. The objectives of our trial were conducted on APP/PSl mice with a period of3mouths drug administration to examine the changes of behavior by three topical behavioral tests. As our expected, we would discover the effective of Panax notoginseng and Geniposide on APP/PS1transgenic mice about improving the abilities of learning and memory abilities. And explore the principles of the compatibility of Panax notoginseng and Geniposode on treating Alzheimer’s disease. The study would provide more scientific evidences on the use of traditional Chinese medicine for clinical practice.2. Material and MethodWe chose male APP/PSl double transgenic mice as the trial subjects. The mice were divided into groups of gardenia, Panax group, compatibility group, transgenic model group, transgenic negative group. The administration drugs were high purity of Geniposide (GP) and Panax notoginseng saponins (PNS). The administration time was started from4-month-old to7-month-old via self-eating ways. The weight and physical changes of mice was observed along with the circumstance during the treatment period. In order to estimate the impact of drugs on mice, Morris water maze, eight-arm maze and passive avoidance test were conducted when7-month-old. We would explore the differences of behavioral performance between each group and attempt to figure the mechanism of compatibility effectiveness out. All the studies will support the Pharmacodynamic hypothesis of Panax notoginsing and Geniposide.3. Results3.1The observation of toxicity of effective components of Panax notginsing and Geniposide as well as their compatibility on APP/PS1transgenic miceRecord showed mice adapted well to the new environment and their body weight increase steadi ly. In the firs t week of administration, body weight showed gentle decline but increased after this period. The body weight of wild mice group increased less than transgenic mice group, and showed significant difference in the late period of administration. There was no significant difference among every transgenic mice group.3.2We conducted all for genetic testing in the trial. Result showed that there are350bp genetic fragment of APPswe products in the transgenic mice. And608bp fragment of PSEN1products was tested in the transgenic mice but every wild mice show negative in these two genes. They indicated that the mice could meet the needs of our trial request.3.3The improvement of effective component of Panax notoginsing and Geniposide as well as their compatibility on the behavior of APP/PS1transgenic3.3.1Morris water maze test results:in the acquisition process, take the latency from the point that mice put into water to the target platform underwater as the evaluat ion of learning and memory abilities. Calculate the average latency of the four quadrants as the concrete values to complete the comparisons. Use Two-way ANOVA analysis, LSD method for comparisons of each group. Results indicated that there were no interaction effects between treatment and time. It means at different points in the timeline, the role of the treatments had the same effect; significant group effect, means at the same point of the timeline, there were significant differences between treatment factors; significant time effect, indicates as the training went on, the time of reaching on the target platform underwater reduced. Results indicated that wild group VS transgenic models day1:P<0.05;day2:P<0.001;day3:P<0.01; day4:P<0.001; day5:P<0.001. Gardenia group vs transgenic model group:day4:P<0.05; day5:P<0.01; Panax notoginsing group VS transgenic model group:day2:P<0.05, day4:P<0.01; Compat ibility of Geniposide and Panax notoginsing group vs transgenic model group: day4:P<0.05, day5:P<0.05.3.3.2Passive avoidance test:using the latency and the times of errors of mice entering the dark part of the facility as the basis for measuring the abilities of learning and memory. The entire trial included the pre-test and the post-treatment drug test, One-way ANOVA analysis showed that showed no significant differences both on latency of entering dark part and t imes of errors step through the equipment (P>0.05).3.3.3Eight-arm maze test, in the acquisition process, the working memory errors of every group reduced wi th the proceeding of training. In day2/3/4/5/6/8, administration groups show significant difference to transgenic model group, and show more capable than transgenic model group in learning and memory abilities. Reference memory, there is no much more difference among groups. Total memory errors, the difference between transgenic model groups and other groups is more significant (P<0.05or P<0.01) in day2/3/4/5/6/8. Administrat ion groups showed well performance in training process. Total time completing the task showed that administration groups spent less time than transgenic model group in the whole training process. In the test, time spent in the preceding feeding arms didn’t show any difference among all the groups. But the time spent in the preceding no feeding arms indicated that every administration groups and wild group spent less time than transgenic model mice and had significant difference.4. Conclusion4.1Morris water maze results indicated that7-months-old transgenic mice have already exposed the decline in learning and memory abilities and suggested administration drugs could effectively improve the APP/PS1transgenic mice’s spatial learning and memory capacity.4.2Passive avoidance test experiment, none of significant difference could be detected both in the pretreatment and protreatment, we speculated it might be the defectiveness of our new trial method or the passive avoidance test was not acute to7-months-old APP/PS1transgenic mice.4.3Eight-arm maze test, in the acquisition process, transgenic model group showed less capable than other groups both working memory errors and total memory errors, as well as in the total time completing the task. It indicated that Geniposide and Panax notoginsing saponin as well as compatibility of them could improve the learning and memory abilities in transgenic mice, especially for compatibility. After training, we checked the time spent in the feeding arms and no feeding arms and the results showed that transgenic model group spent similar proportion of time in them. In contrary, every administration groups and wild group showed less time in the preceding no feeding arms with significant differences or trends. It indicated that our drugs could improve learning and memory defects in transgenic mice.4.4Depend on the results of behavior tests, we can come to the following conclusions:7-month-old mice have showed the deficient performance in learning and memory abilities in Morris Water Maze and Eight Arms Maze; the effective component of Ganiposide and Panax notoginsing can improve learning and memory abilities for APP/PS1transgenic mice; Eight arms maze is more acute than other two behavior tests because of its characteristic. |
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