Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

A network pharmacology approach to investigate the mechanisms of Si-Jun-Zi decoction in the treatment of gastric precancerous lesions

Objective:To find out the potential mechanisms of Si-Jun-Zi(SJZ)decoction in the treatment of gastric precancerous lesions(GPL).Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of SJZ decoction in treating GPL.The compounds and predicted targets of SJZ decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the SJZ decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway enrichment analyses.Results:The results show that 111 compounds and 90 targets were obtained in this work.These targets were further mapped to 654 GO biological process terms and 21 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network,a target-pathways network,and an integrated GPL pathway.These results indicated that SJZ decoction may treat the dysfunctions of GPL mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusions:This work provided a novel approach to understand the pathogenesis of GPL and revealed the therapeutic mechanisms of SJZ decoction,which facilitate the modernization of herbal medicine for complex diseases in the future.

Discussing the six meridional diseases of Shanghan Lun based on stress theory

As the theoretical source of Traditional Chinese Medicine clinical medicine,Shanghan Lun plays a vital role in guiding the diagnosis and treatment of clinical diseases.Stress is a systemic nonspecific and adaptive response that occurs when the body is stimulated by internal and external environmental factors.This paper discusses the correlation between the three phases of stress containing alarm,resistance,and exhaustion and the three yin and three yang diseases.It was concluded that sanyang diseases were related to the alarm stage and resistance stage,and sanyin diseases were related to the failure stage.The results indicated the essence of diseases of six meridians from the perspective of stress and provided reference for the diagnosis and treatment of six classics diseases.

Identification of key pathways and genes from gastric precancerous lesions to gastric cancer by integrated bioinformatics analysis

Objective:This work aimed to illuminate the potential key genes and pathways in GC tumorigenesis based on bioinfOrmatics analysis.Methods:The differentially expressed genes(DEGs)between GPL tissue samples and GC tissue samples were investigated using the GSE55696 and GSE87666 microarray data from the Gene Expression Omnibus(GEO)database.DEGs were identified by an empirical Bayes method based on the Limma R package.Then,KEGG and GO enrichment analyses of DEGs were performed followed by protein-protein interaction(PPI)network construction.Finally,the overall survival(OS)analysis of key genes was performed by the Kaplan-Meier plotter online tool.Results:A total of 250 DEGs were obtained,of which 216 were up-regulated and 34 were down-regulated.KEGG pathways analysis showed that the up-regulated DEGs were enriched in cytokine-cytokine receptor interaction,chemokine signaling pathway,metabolic pathways,PI3K-Akt signaling pathway,NF-kappa B signaling pathway,and other signaling pathways about cancer,while no down-regulated pathways were enriched.A PPI network of DEGs was constructed with 117 nodes and 660 edges,and 20 genes were selected as hub genes owing to high degrees in the network.According to the Kaplan-Meier analysis,6 out of 20 hub genes including CCR7,FPR1,C3,CXCR5,GNB4,and PPBP with high mRNA expression were associated with poor OS for GC patients.Conclusion:The results of this study provide possible factors for the occurrence of GC,and the identification of the genes and pathways associated with the progression from GPL to GC provides valuable data for investigating the pathogenesis in future studies.