Clinical And Network Pharmacology Study Of Yizhi Mixture In The Treatment Of Senile Dementia With Liver And Kidney Deficiency And Insomnia

Objective :To investigate the clinical efficacy of Yizhi mixture for senile dementia with liver and kidney deficiency and insomnia,to elucidate the basic mechanisms using network pharmacology,and to inform clinical treatment.Methods :1.Clinical observation: 70 elderly dementia patients with liver and kidney deficiency who developed insomnia were recruited and randomly divided into a control group and a treatment group,with 35 patients in each group.The control group received donepezil hydrochloride and zopiclone tablets,while the treatment group received Yizhi mixture based on the treatment of the control group.The duration of treatment was 12 weeks.Before and after the treatment of both groups,the following parameters were recorded: the TCM syndrome score,Mini-Mental State Examination(MMSE)score,Activities of Daily Living(ADL)scale score,Pittsburgh Sleep Quality Inventory(PSQI)score,homocysteine(Hcy)level,and apolipoprotein E(Apo E)level.SPSS 25.0 software was used to analyze changes in these parameters and to evaluate the clinical efficacy and safety of Yizhi mixture.2.Network pharmacology research: The TCMSP and ETCM databases were used to screen active compounds and relevant drug targets of Yizhi mixture,and targets of senile dementia and insomnia were searched in Gene Cards and OMIM databases,and potential targets of Yizhi mixture for treatment of senile dementia and insomnia were obtained after cross referencing.Cytoscape 3.7.2 software and the String database were used to construct a drug-disease-target network and a protein-protein interaction(PPI)network to select key targets.Finally,the overlapping targets were imported into the DAVID database for enrichment analysis and the results of the enrichment analysis were visualised using the wechat platform to explore the potential mechanism of action of Yizhi mixture in the treatment of senile dementia with insomnia.Results:1.Clinical observation: There was no significant difference in general data between the two groups before treatment(P > 0.05).From the perspective of treatment effect,the treatment group and the control group could improve the indexes of patients(P < 0.05),but the treatment group was better than the control group in reducing the TCM syndrome score,ADL score,PSQI score,Hcy level,Apo E level and increasing MMSE score(P < 0.05),and the total effective rate was higher than the control group(P < 0.05).2.Network pharmacology research: In total,177 active ingredients,234 potential drug targets,14399 targets for senile dementia and 6718 targets for insomnia were tested.A total of 105 drug and disease cross-targets were identified,of which 22 were important targets.In addition,quercetin,kaempferol and luteolin had the top three rankings,while AKT1,IL6,TNF,IL1 B and VEGFA were the five most important targets.The results of the enrichment analysis included 763 GO functions and 153 KEGG signaling pathways.Conclusion:1.On the basis of conventional treatment,Yizhi mixture can improve the clinical symptoms of senile dementia patients with liver and kidney deficiency combined with insomnia,reduce the TCM syndrome score,ADL score,PSQI score,Hcy level and Apo E level,and improve the MMSE score.The therapeutic effect is much better than with conventional treatment alone,and there are no side effects during treatment.Safety was good.2.Network pharmacology analysis shows that the Yizhi mixture contains quercetin,kaempferol,luteolin and other potent active ingredients that can affect key targets such as AKT1,IL6,TNF,IL1 B,VEGFA.It may play a role in the treatment of senile dementia and insomnia,regulation of AGE-RAGE signaling pathway,TNF signaling pathway,IL-17 signaling pathway and other signaling pathways involved in diabetic complications.