Investigate The Regularity Of Traditional Chinese Medicine Regulating Partial Programmed Cell Death And Intervening Liver Cancer Based On Bioinformatics

Objective: To screen the gene targets,compounds,traditional Chinese medicines and traditional Chinese medicines that mediate autophagy,pyroptosis and iron death intervention in liver cancer by bioinformatics,data mining and molecular docking techniques.Methods: The expression data of HCC were downloaded from the TCGA database and analyzed for differences using the R software "DESeq2" package.Autophagy,pyroptosis and iron death-related genes were collected by searching HADb,GO,GeneCards and FerrDb databases and literatures.Differentially expressed genes of three programmed cell death(PCD)were extracted and subjected to GO,KEGG,and GSEA enrichment analysis.The three PCD differentially expressed genes were uploaded into TCMSP database to match compounds,and the druggable compounds were selected according to ADME parameter screening criteria and Lipinski principle,and the "gene-compound" association network was constructed using Cytoscape,and the core compounds were selected.The three PCD candidates were sequentially uploaded to the TCMSP database to collect the associated herbs,and Cytoscape was used to calculate the herbs with the highest association.Then,the data of traditional Chinese medicine were imported into the traditional Chinese medicine inheritance computing platform V3.0 for medication law calculation and analysis,followed by four qi statistics,five flavors statistics,meridian statistics,and efficacy statistics.In order to further verify the reliability of binding between core target and core compounds,and explore new drug target combinations,Auto Dock was used to verify the molecular docking of core target and compounds.Results: 90 differential genes of autophagy,114 differential genes of pyroptosis and 124 differential genes of iron death were identified.Pathways such as PPAR signaling pathway,arachidonic acid metabolism,IL-17 signaling pathway,and Fox O signaling were enriched,as well as gene sets such as TNFA/VIA/NFKB signaling,inflammatory response,hypoxia response,and interferon-gamma.According to the screening criteria,92 autophagic compounds,268 pyroptotic compounds,and 291 iron death compounds were identified,and topological analysis of the "gene-compound" interaction network selected the core compounds,including quercetin,luteolin,cryptotanshinone,laccarin,wogonin,and kaempferol.335autophagy-associated herbs,249 pyropsis-associated herbs and 274iron-death-associated herbs were collected from TCMSP database.Cytoscape software was used to construct the "gene-compound-traditional Chinese medicine" association network of three PCDs in turn.High-value herbs were selected by topological analysis,including Salvia miltiorrhiza,Scutellaria barbata,Patrinia,Baibu,Corydalis yanhusuo,Prunella vulgaris,Glycyrrhiza uralensis,Scutellaria baicalensis,Dalbergia odorifera,and Bupleurum chinense.The analysis of the regularity of traditional Chinese medicine regulating the three PCDs in the intervention of liver cancer showed that the regularity of the four qi was mainly cold,warm,and flat,and bitter,pungent,and sweet drugs appeared more frequently in the five flavors,and the drugs were attributed to the liver meridian,lung meridian,kidney meridian,spleen meridian,and stomach meridian in turn,and the efficacy distribution of the drugs was mainly heat-clearing and detoxifying drugs,tonifying deficiency drugs,promoting blood circulation and removing blood stasis drugs,and relieving exterior drugs.Twenty-two gene targets and 11 compound ligands were included,respectively.The results of molecular docking showed that the binding energies were less than-5 kcal/mol,and HMOX1,MMP1,DRD4,AKR1C3,cryptotanshinone,tanshinone ⅡA and quercetin had significant binding activities with other molecules.Conclusion: This study systematically analyzes the relationship between the regulation of three PCDs by traditional Chinese medicines and liver cancer,and the results show that multiple traditional Chinese medicines can mediate autophagy,pyroptosis and iron death to intervene the course of liver cancer,which involves a variety of compounds and gene targets,and molecular docking verifies the reliability of traditional Chinese medicines targeting PCD targets.This study shows the great potential of traditional Chinese medicine in regulating PCD in the treatment of liver cancer,which can provide some reference value for subsequent experimental studies and clinical medication.