Study On The Mechanism Of Anti Hepatoma Effect Of Dutan Yuxu Fang Based On Network Pharmacology

ObjectiveTo explore the effectiveness of TCM treatment of liver cancer from toxic phlegm and blood stasis of spleen and kidney deficiency and to preliminarily analyze the possible mechanism of action through network pharmacology.This research is carried out from two levels: at the animal level,the effect of complete prescription of Dutan Yuxu Fang on the growth rate,apoptosis rate and invasion of liver cancer tissue was analyzed,and the effectiveness of Dutan Yuxu Fang in the treatment of liver cancer was evaluated;through network pharmacology analysis,the "component target" network of Dutan Yuxu Fang in the treatment of liver cancer was obtained,and the biological pathway essence of Dutan Yuxu Fang in the treatment of liver cancer was discussed.MethodsPart Ⅰ: To compare the effects of dutan yufang and Dutan Yuxu Fang on the growth,apoptosis and invasion of liver cancer in mice with negative serum group and sorafenib group as control.SPSS 26.0 software was used for statistical analysis.All data were expressed as mean ± standard deviation(x±s).Univariate analysis of variance was used for comparison among groups,and LSD test was used for pairwise comparison between groups.All statistical tests were performed by two-sided test,P< 0.05 was statistically significant.Part Ⅱ: the adoption Onco DB.HCC,liverome and other databases were searched to collect disease targets related to liver cancer.Using pharmacokinetic ADME parameters as screening criteria,the active components of Dutan Yuxu Fang were screened in tcmsp,and the potential targets of the active components were obtained by pharmmapper.After the above targets were sorted out by excel2016,the predictive targets of Dutan Yuxu Fang in the treatment of liver cancer were obtained.The interaction network between active ingredients and therapeutic targets of Dutan Yuxu Fang was constructed by using Cytoscape.The topological structure of the constructed network was analyzed by "Tools Network Analyzer" plug-in.Finally,the gene of the predictive targets was analyzed by using Clue GO plug-in The prediction of gene enrichment and related signal analysis of gdtg pathway are involved in the process of biological therapy.ResultPart Ⅰ: In the apoptosis experiment,compared with the blank control group,Dutan Yuxu Fang could significantly promote tumor cell necrosis,increase the apoptosis index of tumor cells(P<0.01),and significantly reduce the MVD in tumor(P<0.01).Part Ⅱ: through searching TTD,drugbank Onco DB.HCC and Liverome database,A total of 519 liver cancer related targets were obtained.159 active components of Dutan Yuxu Fang were screened in TCMSP database with OB≥30%,DL≥0.18 and HL≥4.00 as parameters.Pharmmapper was used to obtain the potential targets of each active component and map them with liver cancer targets.146 predictive targets of Dutan Yuxu Fang in the treatment of liver cancer were obtained.According to the analysis of GO biological process and KEGG pathway enrichment with P<0.001,there were44 biological processes involved in 146 predictive targets of HCC,including positive regulation of cell migration,protein tyrosine kinase activity,ERK1 and ERK2 cascade,transmembrane receptor protein tyrosine kinase activity,phosphatidylinositol mediated signal transduction,response to corticosteroids,epithelial cell apoptosis Regulation of cell proliferation,response to glucocorticoid,regulation of phospholipase activity,positive regulation of epithelial cell migration and endothelial cell migration,exogenous apoptotic signal pathway lacking ligand,etc.It is involved in the regulation of 30 signaling pathways,including cancer signaling pathway,proteoglycan in cancer,central carbon metabolism in cancer,PI3 K Akt signaling pathway,Rap1 signaling pathway,tumor necrosis factor signaling pathway,apoptosis,cell cycle,etc.ConclusionDutan Yuxu Fang can significantly promote the necrosis of liver cancer tissue,induce apoptosis of liver cancer cells and reduce MVD value of liver cancer tissue.Through the network pharmacology analysis of Dutan Yuxu Fang,it is found that the compound may play an anti hepatoma effect through cancer signaling pathway,protein polysaccharide in cancer,central carbon metabolism of cancer,PI3 K Akt signal pathway,Rap1 signal pathway,hepatitis B,RAS signal pathway,micro RNAs in tumor,estrogen signal pathway,HIF-1 signal pathway,vascular endothelial growth factor signaling pathway,etc.It shows that Dutan Yuxu Fang can play a role in the treatment of liver cancer from multiple targets,angles and levels,which provides a direction for further experimental research of Dutan Yuxu Fang in the future.