| Objective:Based on Meta-analysis,systematically evaluate the efficacy and safety of Huanglian Wendan Decoction in treating insomnia of phlegm-heat disturbing heart type,and use network pharmacology to predict the mechanism of action of Huanglian Wendan Decoction in treating insomnia.Methods:1 Randomized controlled trials on the treatment of insomnia with Huanglian Wendan Decoction published before January 31,2023 were searched in CNKI,Wanfang,VIP and other medical databases.The literature was screened strictly according to the inclusion criteria,and the basic information and data were extracted.The quality of the literature was assessed according to the Cochrane Handbook of Risk Assessment.Use the Rev Man5.4 software to conduct meta-analysis on the clinical total effective rate,Pittsburgh sleep quality index,traditional Chinese medicine syndrome score,sleep status self-evaluation scale and other outcome indicators.2 The TCMSP database was used to search for active ingredients in Huanglian Wendan Decoction,and its related targets were predicted,and the Uniprot protein database was used for verification and correction.Insomnia-related genes were obtained from OMIM,Pharm Gkb,TTD,Drug Bank,and Gene Cards databases,and Venn diagrams were drawn using an online mapping platform after removing duplicate genes.The obtained intersection genes were imported into Cytoscape software to draw a network diagram of active ingredients and gene targets,and at the same time imported into the STRING database to construct a PPI network diagram.GO functional enrichment and KEGG pathway enrichment analysis were performed using the Metascape database.Results:1 Meta-analysis: A total of 18 literatures were included in this study,with a total of 1521 insomnia patients.Among them,there were 766 cases in the test group and 755 cases in the control group.Meta-analysis results showed that Huanglian Wendan Decoction combined with conventional western medicine was superior to western medicine alone in improving the total clinical effective rate,Pittsburgh sleep quality index score,quality of life index score,and peripheral blood 5-HT and β-EP concentrations.At the same time,it has a remarkable effect in improving the syndrome score of traditional Chinese medicine and reducing the occurrence of adverse reactions.The differences in each outcome index were statistically significant.The analysis of publication bias suggests that the funnel plot is asymmetrical and there may be some publication bias.2 Network pharmacology research: By TCMSP screening,128 active ingredients and 247 related targets of Huanglian Wendan Decoction for insomnia were obtained.Main active ingredients: quercetin,naringin,β-sitosterol,baicalin,tangerine,luteolin,7-hydroxy-4’-methoxy-isoflavone,alfalfa,7-methoxy-2-methyl isoflavone,kaempferol.Use STRING software to draw PPI network diagram.The top 10 key targets of Degree extraction were IL1 B,CAT,CASP3,PTGS2,CREB1,VEGFA,PPARG,ESR1,MAPK3 and CXCL8.By GO functional enrichment analysis,1295 Biological processes(BP),92 Cellular components(CC),and 129 Molecular functions(MF)were obtained.KEGG pathway enrichment analysis showed 92 related pathways,which were mainly involved in the interaction between neuroactive ligand and receptor,calcium signaling pathway,AGE-RAGE signaling pathway,c GMP-PKG signaling pathway,hydroxytamineergic synapses,and IL-17 signaling pathway.Conclusions:1 The therapeutic effect of Huanglian Wendan Decoction combined with Western medicine in the treatment of phlegm-heat disturbed cardiac insomnia is better than that of Western medicine alone.However,due to the low quality of the included references and certain publication bias,the relevant outcome indicators are heterogeneous.In the future,high-quality and large sample RCT literature is still needed for verification.2 Huanglian Wentan Decoction plays its role through multi-component,multi-target and multi-channel synergistic relationship,and its mechanism may be that the active components of quercetin,naringin,β-sitosterol,baicalein,etc.act on the targets of IL1 B,CAT,CASP3,PTGS2,etc.At the same time,it is related to the regulation of neural active ligand-receptor interaction,calcium signaling pathway,serotonergic synapses,c AMP signaling pathway,AGE-RAGE and other signaling pathways.However,the data in this study were all from the network,which may lead to partial bias in the results,and further molecular docking and clinical verification need to be completed. |
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