Molecular mechanisms of Biyu decoction as treatment for psoriasis:A network pharmacology and molecular docking study

BACKGROUND The therapeutic effects of a combination of Chinese medicines called Biyu decoction have been clinically verified,although its molecular targets in psoriasis remain unknown.AIM To explore the molecular mechanisms of Biyu decoction for psoriasis treatment.METHODS In this network pharmacology and molecular docking study,the Traditional Chinese Medicine Systems Pharmacology database was searched for Biyu decoction active ingredients.GeneCards,Online Mendelian Inheritance in Man,PharmGkb,Therapeutic Target Database,and DrugBank databases were searched for psoriasis-related genes.The genes targeted by the decoction’s active ingredient and disease genes were intersected to obtain predictive targets of the drug during psoriasis treatment.Cytoscape 3.8.0 was used to construct a drug component/target disease network.The The functional protein association networks database and Cytoscape were used to construct a protein-protein interaction network and streamline the core network.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for pathway enrichment analysis.Molecular docking technology was used to verify the drug component/target disease network.RESULTS We screened 117 major active ingredients,including quercetin,kaempferol,naringenin,and acetyl-shikonin,and identified 213 gene targets,such as MAPK3,JUN,FOS,MYC,MAPK8,STAT3,and NFKBIA.Using a molecular docking analysis,the main active ingredients demonstrated good binding to the core targets.The Gene Ontology analysis showed that these ingredients were significantly associated with biological activities,such as transcription factor DNA binding,RNA polymerase II-specific DNA binding of transcription factors,and cytokine receptor binding;responses to lipopolysaccharides,molecules of bacterial origin,and oxidative stress;and were mainly distributed in membrane rafts,microdomains,and regions.The Kyoto Encyclopedia of Genes and Genomes analysis showed that decoction ingredients act on Th17 cell differentiation,tumor necrosis factor and mitogen-activated protein signaling pathways,the interleukin-17 signaling pathway,and the PI3K-Akt signaling pathway.CONCLUSION Biyu decoction may be effective against psoriasis through multi-component,multi-target,and multi-channel synergy.

Constructing protein-protein interaction network of hypertension with blood stasis syndrome via digital gene expression sequencing and database mining

OBJECTIVE： To construct a protein-protein interaction（PPI） network in hypertension patients with blood-stasis syndrome（BSS） by using digital gene expression（DGE） sequencing and database mining techniques.METHODS： DGE analysis based on the Solexa Genome Analyzer platform was performed on vascular endothelial cells incubated with serum of hypertension patients with BSS. The differentially expressed genes were f iltered by comparing the expression levels between the different experimental groups. Then functional categories and e nriched pathways of the unique genes for BSS were analyzed using Database for Annotation, Visualization and Integrated Discovery（DAVID） to select those in the enrichment pathways. I nterologous Interaction Database（I2D） was used to construct PPI networks with the selected genes for hypertension patients with BSS. The potential candidate genes related to BSS were identif ied by comparing the number of relationships among genes. Confi rmed by quantitative reverse transcription-polymerase chain reaction（q RTPCR）, gene ontology（GO） analysis was used to infer the functional annotations of the potential candidate genes for BSS.RESULTS： With gene enrichment analysis using DAVID, a list of 58 genes was chosen from the unique genes. The selected 58 genes were analyzed using I2 D, and a PPI network was constructed. Based on the network analysis results, candidate genes for BSS were identifi ed：DDIT3, JUN, HSPA8, NFIL3, HSPA5, HIST2H2 BE, H3F3 B, CEBPB, SAT1 and GADD45 A. Verif ied through qRT-PCR and analyzed by GO, the functional annotations of the potential candidate genes were explored.CONCLUSION： Compared with previous methodologies reported in the literature, the present DGE analysis and data mining method have shown a great improvement in analyzing BSS.

Network pharmacology assessment of Qingkailing injection(清开灵注射液)treatment of cholestatic hepatitis

OBJECTIVE:To investigate the targets and mechanisms of action of Qingkailing injection(清开灵注射液,QKL)in the treatment of cholestatic hepatitis.METHODS:A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis,respectively.The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit.The org.Hs.eg.db and cluster Profiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,which explored biological functions and pathways of potential targets.Targets were then visualized using Cytoscape 3.6.0 software.RESULTS:We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis.QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms,15 cellular component and 29 molecular function terms.The mechanism of QKL action was mainly related to tumor necrosis factor,mitogen-activated protein kinase,and PI3 K-Akt signaling pathways.CONCLUSION:The treatment of cholestatic hepatitis by QKL involved multiple targets,biological functions,and signaling pathways that are closely associated with the disease.