The Effect Of Qizhi Tongluo Capsule On Improving Memory Impairment Caused By Scopolamine In Mice

Objective:The chemical composition,target and pathway of network pharmacology were used to predict the improvement of memory impairment in mice.On the basis of network pharmacology,the pharmacodynamics of the mouse model of memory impairment caused by scopolamine hydrobromide was studied,and the effect of Qulu-Tongluo capsule on memory impairment was proved.Combined with serum biochemical test of model mice and gene expression in cerebral cortex and hippocampus of mice,the pharmacodynamics and mechanism of action were clarified,providing scientific basis for clinical medication of Qizhi Tongluo capsule.Methods:1.Study on network pharmacology of Qizhi Tongluo Capsule to improve memory disorderThe databases like TTD(Therapeutic TargetDatabase),Drugbank and DisGeNET were used to retrieve information about disease targets,while the chemical constituents of Qizhi Tongluo capsule were obtained through databases such as TCMSP and TCMID.The potential active components were screen by using the “drug-like five principles ” to predict and collect the action targets of active components.And finally,the network of how the drug targets and disease targets of active ingredient will interact will be set up.GO analysis and KEGG enrichment analysis were used to study the biological effects and pathways of Qizhi Tongluo capsule in improving memory impairment.2.Study on effect and mechanism of Qizhi Tongluo Capsule to improve memory disorder based on network pharmacologyOn the basis of network pharmacology,the pharmacodynamics and mechanism of action were studied.The SPF grade ICR mice were randomly divided into six groups,namely,normal group,model group,Piracetam positive group and Qizhi Tongluo capsule low,medium and high dose group by body weight.To establish a memory disorder model,the blank group was only injected with normal saline,while the other groups were injected with 3 mg/kg scopolamine injection solution in avolume of 0.1 mL/10 g.After 4 weeks of continuous gavage,the the memory ability of mice will be tested in behavioral experiment.By the end of the behavior,the mouse brain tissue and serum were used to detect biochemical indexes.Finally,it shows that the contents of GSH,GSH-px,GLu,AchE,CHAT activity and SOD and MDA were determined by the kit.The gene expression of M1 receptor and CHAT in mouse hippocampus will be detected with real-time fluorescence quantitative PCR technology.Results:1.Study on network pharmacology of Qizhi Tongluo Capsule to improve memory disorderThrough the analysis of network pharmacology,39 active ingredients and 118 predicted targets of Qizhi TonGLuo capsule were obtained to improve memory impairment.After the analysis and selection of network topology,11 active ingredients and 16 key targets were selected.According to KEGG pathway enrichment,the working principle of Qizhi Tongluo capsule in improving mice's memory impairment seems to relate to seven signaling pathways,such as Cholinergic synapse and Alzheimer's disease and the other.2.Study on effect and mechanism of Qizhi Tongluo Capsule to improve memory disorder based on network pharmacologyIn the behavioral experiment,compared with the model group,animals in the high,medium and low dose groups of Qizhi TonGLuo capsule in the platform experiment made fewer mistakes than those in the model group,and the total time of animals in the stimulus area was shorter those in the model group,and there was a significant difference(P<0.05 or P<0.01).In the navigation experiment of water maze location,compared with the model group,the mice in the high,medium and low dose groups of Qizhi TonGLuo capsule had a better journey through the third quadrant,a longer stay in the third quadrant,and a better crossing times on the platform than those in the model group,while the incubation period was shorter in each administration group than in the model group,and the experimental results were significantly different(P<0.05 or P<0.01).In the water maze space search experiment,compared with the model group,mice in the high,medium and low dose groups ofQizhi TonGLuo capsule passed through the third quadrant,stayed in the third quadrant and passed through the platform more than those in the model group,and the experimental results were significantly different(P<0.05 or P<0.01).Qizhi TonGLuo capsule can significantly increase the content of SOD in mouse serum and CHAT,GSH and GSH-px in mouse brain tissue,and make the content of MDA,AchE and GLu.The results of real-time fluorescence quantitative PCR showed that Qizhi Tongluo capsule could improve the expression of M1 receptor and CHAT genes in hippocampal tissues of mice.Conclusion:In this study,through studying the efficacy and mechanism of Qizhi Tongluo capsule in improving memory impairment,it was confirmed that Qizhi Tongluo capsule could significantly improve memory impairment caused by scopolamine in mice,and its mechanism might be related to the regulation of Cholinergic synapse signaling pathway by Qizhi Tongluo capsule.