A systematic study of Erzhu Erchen decoction against damp-heat internalized type 2 diabetes based on data mining and experimental verification

Background:Erzhu Erchen decoction(EZECD),which is based on Erchen decoction and enhanced with Atractylodes lancea and Atractylodes macrocephala,is widely used for the treatment of dampness and heat(The clinical manifestations of Western medicine include thirst,inability to drink more,diarrhea,yellow urine,red tongue,et al.)internalized disease.Nevertheless,the mechanism of EZECD on damp-heat internalized Type 2 diabetes(T2D)remains unknown.We employed data mining,pharmacology databases and experimental verification to study how EZECD treats damp-heat internalized T2D.Methods:The main compounds or genes of EZECD and damp-heat internalized T2D were obtained from the pharmacology databases.Succeeding,the overlapped targets of EZECD and damp-heat internalized T2D were performed by the Gene Ontology,kyoto encyclopedia of genes and genomes analysis.And the compound-disease targets-pathway network were constructed to obtain the hub compound.Moreover,the hub genes and core related pathways were mined with weighted gene co-expression network analysis based on Gene Expression Omnibus database,the capability of hub compound and genes was valid in AutoDock 1.5.7.Furthermore,and violin plot and gene set enrichment analysis were performed to explore the role of hub genes in damp-heat internalized T2D.Finally,the interactions of hub compound and genes were explored using Comparative Toxicogenomics Database and quantitative polymerase chain reaction.Results:First,herb-compounds-genes-disease network illustrated that the hub compound of EZECD for damp-heat internalized T2D could be quercetin.Consistently,the hub genes were CASP8,CCL2,and AHR according to weighted gene co-expression network analysis.Molecular docking showed that quercetin could bind with the hub genes.Further,gene set enrichment analysis and Gene Ontology represented that CASP8,or CCL2,is negatively involved in insulin secretion response to the TNF or lipopolysaccharide process,and AHR or CCL2 positively regulated lipid and atherosclerosis,and/or including NOD-like receptor signaling pathway,and TNF signaling pathway.Ultimately,the quantitative polymerase chain reaction and western blotting analysis showed that quercetin could down-regulated the mRNA and protein experssion of CASP8,CCL2,and AHR.It was consistent with the results in Comparative Toxicogenomics Database databases.Conclusion:These results demonstrated quercetin could inhibit the expression of CASP8,CCL2,AHR in damp-heat internalized T2D,which improves insulin secretion and inhibits lipid and atherosclerosis,as well as/or including NOD-like receptor signaling pathway,and TNF signaling pathway,suggesting that EZECD may be more effective to treat damp-heat internalized T2D.

A bioinformatics-based study of the mechanism of JQ-1 on BET protein and atherosclerosis induced by vascular smooth muscle cell proliferation

Background:Based on previous theoretical studies,JQ-1 as a common inhibitor of bromodomain and extraterminal(BET)proteins was used to treat a variety of diseases.Therefore,we aimed to explore the mechanism of action of JQ-1 on BET proteins based on bioinformatics and build the novel hypothesis of JQ-1 in treating atherosclerosis(AS)caused by proliferation of vascular smooth muscle cells(VSMCs).Methods:We selected the chip GSE138323 which was searched with the key words“Vascular smooth muscle cell proliferation”in Gene Expression Omnibus(GEO)database,and differential gene analysis was performed between the GRO and JQ-1 groups.Then the top twenty significantly up-regulated genes and the top twenty significantly down-regulated genes were selected for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Thirdly,structured the PPI network of forty differential genes,and the core genes were screened by using the MCC algorithm which in“Cytohubba”plugin in the Cytoscapev3.9.1 software.After that,single gene Gene Set Enrichment Analysis(GSEA)enrichment analysis was performed on the selected core genes in R language.Finally molecular docking validation was performed.Results:Five core genes was selected:H3C2,H3C4,H3C7,H3C10 and AREG.The GO enrichment analysis results showed that there were twenty-five entries in biological process,eight entries in cellular components(CC),and twenty-five entries in molecular function.The KEGG enrichment analysis results showed that there were seven pathways,mainly including systemic lupus erythematosus and external neutrophil trap formation.The GSEA results showed that the five genes were mainly through the regulation of cytochrome P450 metabolism,PPAR signaling pathway and other pathways.The molecular docking results showed that JQ-1 had binding activity with these five genes.Conclusions:JQ-1 may regulate the expression of the genes that H3C2,H3C4,H3C7,H3C10 and AREG,to mainly regulate the genes in cytochrome P450 metabolism,PPAR singling pathway and other pathways,to make some influence in the proliferation of VSMCs,and improved atherosclerotic symptoms due to vascular smooth muscle proliferation,thus treating cardiovascular disease.

Network pharmacology and molecular docking techniques to explore the mechanism of Smilax china L.in the treatment of myocardial infarction

Objective:To predict the relevant targets and signaling pathways of Smilax china L.(SC)for treating myocardial infarction on the basis of network pharmacology and molecular docking.Consequently,the basis for additional in-depth investigation is obtained.Methods:First,the targets of SC and the targets for treating myocardial infarction were screened from different databases,Then the intersection genes of SC for treating myocardial infarction were performed in Venny 2.1.0.Second,to obtain the protein interaction network,the Metascape database,String database,were used to analyze the important modules related to the signaling pathway using MCODE algorithm.Furthermore,the DAVID database was used for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.And we constructed the“interaction targets-pathways”network by Cytoscape software,and using Network Analyzer was used to screen the core compound,core targets and core pathways.Finally,molecular docking was used to verify whether the core compounds and core targets had better docking binding.Results:11 active ingredients and 98 targets of SC,1846 targets to treat myocardial infarction and 58 targets related to treat myocardial infarction in SC were obtained;MCODE analysis of the protein-protein interaction network yielded 4 important modules related to signaling pathways;Gene Ontology enrichment analysis yielded 848 entries and Kyoto Encyclopedia of Genes and Genomes enrichment analysis yielded 144 signaling pathways;the core compounds were beta-sitosterol,diosgenin,kaempferol,core targets were AKT1,CASP9,BCL2,core pathways were pathways in cancer,pathways of neurodegeneration-multiple diseases,Kaposi’s sarcoma-associated herpesvirus infection,lipid and atherosclerosis and human cytomegalovirus infection.Finally,molecular docking between core components and core targets was verified.Conclusion:The preliminary prediction of the mechanism of the SC in the treatment of myocardial infarction is that it acts through a multi-compounds,multi-targets and multi-pathways.This study provided a theoretical basis and research direction for the mechanism of action of SC in the treatment of myocardial infarction,and lays the foundation for further research on SC in the treatment of myocardial infarction.