Experimental Study On Buyang Huanwu Decoction In The Treatment Of Vascular Dementia Based On Network Pharmacology

Objective: To explore the mechanism of Buyang Huanwu Decoction in the treatment of vascular dementia from the perspective of molecular biology through network pharmacology and molecular docking technology,and to verify the results through animal experiments,so as to provide new insights for future experimental research and clinical application.Clues to enrich the theoretical basis of Buyang Huanwu Decoction in the treatment of vascular dementia.Methods:1.Network pharmacology research: Use TCMSP,traditional Chinese medicine and active ingredient database to collect the active ingredients of Buyang Huanwu Decoction composed of 7 traditional Chinese medicines,supplement with literature,and use Pub Chem,Swiss Target Prediction database to predict the target of active ingredients.The targets of vascular dementia were screened through Gene Cards databases,Drugbank,and OMIM,and the screening of intersection targets was carried out on the Weishengxin cloud platform.Construct the PPI network in the string database,use Cyto Scape to analyze the topology of the PPI network to obtain the core targets,draw a "disease-Chinese medicine-ingredient-target" network diagram on this basis,and analyze the core components at the same time.Use the Metascape database to conduct GO and KEGG pathway enrichment analysis on the intersection targets,and visualize them through the We Chat platform.Use Cyto Scape software to build a "disease-traditional medicine-compoundtarget-pathway" network diagram.Finally,the molecular docking technology was used to verify the combination of the simulated core components and the core targets,and to verify the results of network pharmacology.2.Animal experimental research: The VaD rat model was established by the reperfusion combined with bilateral common carotid artery ligation method,and Buyang Huanwu Decoction was used to intervene to observe the therapeutic effect and explore the mechanism of action.Ten healthy SD rats were randomly selected as the sham operation group,and the rest of the rats were subjected to VaD mode-ling.One week later,the Morris water maze was used to test whether the rats were successfully modeled.The rats successfully modeled were randomly divided into a model group and a traditional Chinese medicine group,with 10 rats in each group.The rats in the traditional Chinese medicine group were treated with Buyang Huanwu Decoction,and the rats in the sham operation group and the model group were given intragastric administration of equal volume of normal saline.After 4 weeks of continuous treatment,the Morris water maze test was performed on the rats in each group.After the end,the brain tissue of the rats was stained with HE to observe the morphology of neurons,and the expression levels of PI3 K and Akt mRNA in the hippocampal tissue were detected.Results:Network pharmacology: Buyang Huanwu Decoction contains 7 traditional Chinese medicines,with a total of 82 active ingredients and 804 corresponding targets.23 core targets including SRC,MAPK3,PIK3R1,PIK3 CA,AKT1,etc.and 5 core active ingredients(baicalein,kaempferol,quercetin,β-sitosterol)were screened out through string database and Cytoscape software,ferulic acid).The enrichment analysis results of biological processes showed that the treatment of vascular dementia by Buyang Huanwu Decoction was mainly related to nitrogen compounds,phosphorylation,MAPK cascade,cell migration,kinases,hormones,inflammatory response,synapses,neurons,etc.KEGG enrichment analysis mainly focuses on PI3K/Akt signal pathway,MAPK signal pathway,neurotrophin signal pathway,HIF-1 signal pathway,apoptosis and other signal pathways,among which PI3K/Akt signal pathway may be one of the most key pathways of Buyang Huanwu decoction in the treatment of VaD.Animal experiments: Morris water maze test results showed that in the positioning navigation test,the escape latency of rats in the model group was significantly higher than that of the sham operation group(P<0.05);compared with the model group,the escape latency of rats in the Chinese medicine group was Significantly shortened(P<0.05).In the space exploration experiment,the number of times the rats crossed the platform and the dwell time in the target quadrant of the model group were significantly less than those in the sham operation group(P<0.05);compared with the model group,the number of times the rats crossed the platform and the dwell time in the target quadrant were increased in the Chinese medicine group(P<0.05).HE staining showed that compared with the rats in the sham operation group,the number of hippocampal neurons in the model group decreased and the number of abnormal shapes increased;the number of neurons in the Chinese medicine group increased and the number of neurons with abnormal shapes decreased compared with the model group.The results of RT-qPCR showed that the contents of PI3 K and AktmRNA in the hippocampal tissue of the model group were lower than those in the sham operation group(P<0.05).Conclusion: Through the study of network pharmacology,it is found that Buyang Huanwu decoction is multi-target,multi-component and multipathway in the treatment of vascular dementia,and its mechanism may be related to PI3K/Akt signal pathway,MA-PK signal pathway,neurotrophin signal pathway,HIF-1 signal pathway,apoptosis and other signal pathways,among which PI3k/Akt signal pathway may be one of the most important pathways in the treatment of vascular dementia.Combined with animal experimental studies,Buyang Huanwu decoction may play a role in the treatment of vascular dementia by activating PI3K/Akt signal pathway,thus improving the cognitive dysfunction of vascular dementia rats.