| Backgroundand Objective:Traditional Chinese medicines formula Shenzhi Ling recorded in Beiji Qianjin Yaofang by the "ginseng,Poria,Polygalaceae,Shichangpu",It was taken from the classic traditional Chinese medicine DingZhiXiaoWan,and its main treatment is similar to the depression in modern medicine theory.In our previous study,we have made clear that Shenzhi Ling could significantly increase the survival rate of SY5Y cells damaged by corticosterone,increase the content of nerve growth factor NGF and neurotrophic factor BDNF in the hippocampus of rats,and regulate the level of monoamine transmitters in the brain of CUMS rats,improve behavioral indicators of CUMS rats,suggest it has clear effect of antidepressant.With special attention,Shenzhi Ling can improve cognitive function with injured by different models,improve cognitive function ability of rats and mice,and its effection is dependent with dose.Shenzhi Ling can also improve the liver glycogen and muscle glycogen of exercise induced fatigue mice,and reduce the concentration of lactic acid in muscle.It shows that Shenzhi Ling has the effect of anti-fatigue.And the preclinical pharmacology and toxicology study of Shenzhi Ling conform to the requirements of clinical trials,and clinical research approval has been obtained.This study will be used to evaluate the effectiveness and safety of antidepression,improving disgnosia and relieving fatigue in the treatment of Shezhi Ling by using a random,double-blind,double-simulation and positive drug control method.In this study,we hope that the serotonin reuptake effect of Shenzhi Ling is studied through animal level and cell level,to study the effects of Shenzhi Ling of the role of 5-HT system in animal brain,to explore the regulation mechanism of Shenzhi Ling on 5-HT system.Methods:?By HAMD,TCM score,SDS and EEG,the effectiveness of Shenzhi Ling in improving mild/moderate depression was evaluated,and through the follow-up and safety checks,evaluation of the safety of Shenzhi Ling.?Evaluation of the efficacy of Shenzhi Ling tablets in improving cognitive dysfunction by N-Back test and EM test;? Through the evaluation of brain function and the test of autonomic nervous system balance,evaluate the ability of Shenzhi Ling tablets to improve the fatigue state;?On the basis of above,combined with EEG,we can analyze the target and mechanism of Shenzhi Ling tablets;In this study,we established CUMS rat model,observed the effection of different doses of Shenzhi Ling on the behavioral indexes of depressive rats after 3 weeks,observed the effection of HPLC on the content of 5-HT in hippocampus,observed PCR method the effection of Shenzhi Ling on the expression of miR-16 and SERT mRNA in hippocampus of CUMS rats.Results:clinical trials results:?The results showed that Shenzhi Ling tablets could significantly improve the HAMD score,TCM score,SDS score,while regulating a variety of central neurotransmitter levels,and there was no obvious adverse reaction;?The accuracy rate of 1-Back project in N-Back of Shenzhi Ling Group was significantly improved,the gaze time of EM test was significantly improved and the RSS of eye movement test was significantly decreased;? The brain function of Shenzhi Ling group was significantly improved in fatigue,and there was no significant change in the balance of the autonomic nervous system;?After 8 weeks of treatment,the level of GLU in the brain of Shenzhi Ling group was significantly reduced,the level of NE and 5-HT increased significantly,the level of 5-HT of Fluoxetine group was significantly improved;?There was no significant difference in biochemical indexes from before to after treatment,and no obvious adverse reactionThe effection of Shenzhi Ling on the reuptake of 5-HT:300 mg/kg and 600 mg/kg of Shen Zhi Ling could significantly improve the behavioral index of CUMS rats and increase the level of 5-HT in hippocampus of rats.At the same time,it could increase the expression of miR-16 and decrease the expression of SERT mRNA in hippocampus of rats.The cell experiments of Primary hippocampal neurons in rats,100?g/ml?200 ?g/ml 500 ?g/ml Shenzhi Ling significantly increased the expression of miR-16 in the cells with corticosterone/glutamate injured cell model.And Shenzhi Ling can significantly decreased the expression of SERT by the above models.Conclusion:The results of clinical trials show that,Shenzhi Ling has a significant antidepressant effect,Its role in a variety of central neurotransmitters,Adverse reactions compared to the control group less,In the attention and memory of cognitive impairment improved significantly,In the brain area of fatigue has significantly improved.The results of EEG shows,Shenzhi Ling can simultaneously antidepression by act on various of monoamine transmitters.The results of the basic experiment show that,by up-regulating the expression level of miR-16,Shen Zhi Ling release its inhibitory effect on the target gene SERT,inhibit the reuptake of 5-HT,and then increase the level of 5-HT in the brain of model rats,to combat with depression. |
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