Prediction and validation of molecular biological mechanism of Fuzheng Huayu capsule in the treatment of liver cancer

Background:Fuzheng Huayu capsule(FZHY)combined with antiviral treatment has been shown to significantly reduce the risk of liver cancer in patients with hepatitis B cirrhosis.However,the potential of FZHY to directly treat liver cancer remains largely unknown.This study aims to investigate the molecular mechanism underlying the potential of FZHY in treating liver cancer.Methods:A network pharmacological analysis was performed using the Traditional Chinese Medicine Systems Pharmacology database to identify FZHY compounds and targets.Disease targets were searched using the Genecards database,and transcriptome data was downloaded from the NCBI database.Gene Ontology analysis was conducted using the DAVID database,and Kyoto Encyclopedia of Genes and Genomes analysis was based on KOBAS and bioinformatics methods.The Swissdock database was used for molecular docking.In cell experiments,the half inhibitory concentration(IC50)of FZHY was determined using the CCK8 method.The effects of FZHY on cell viability,apoptosis,and mitochondrial membrane potential were evaluated using a fluorescence microscope and flow cytometry.The molecular mechanism of FZHY in treating liver cancer was verified using quantitative polymerase chain reaction.Results:A total of 127 compounds and 184 proteins were identified as potential active ingredients and putative liver cancer-related targets.Additionally,1,899 liver cancer targets,279 transcriptome targets,and 3 pathways(p53 signaling pathway,apoptosis and PI3K-Akt pathway)were collected.The FZHY-targets-liver cancer interaction network was constructed.IC50 of FZHY lyophilized powder solution to liver cancer was 5.13 mg/mL(IC50=5.13 mg/mL).FZHY treatment led to an increase in the ratio of cell apoptosis and induced mitochondrial membrane potential damage,resulting in an increase in the number of dead cells.The expression levels of CCNB1 and BIRC5 were induced with FZHY treatment,while the expression levels of AKR1C3 and IGF2 were reduced.Conclusion:FZHY promotes apoptosis of liver cancer cells by acting on the p53 signaling pathway,apoptosis,and PI3K-Akt pathway.CCNB1,BIRC5,AKR1C3,and IGF2 are potential target proteins for FZHY in treating liver cancer.

Fuzheng Huayu Capsule Improves Survival in Patients with HepatitisB-related Cirrhosis and Overt Hepatic Encephalopathy

Objective:Fuzheng Huayu(FZHY)capsules exert anti-liver fibrosis and cirrhosis effects.This study aimed to determine the effect of FZHY on the 6-month survival rate of patients with overt hepatic encephalopathy(OHE)and hepatitis B-related cirrhosis(HBC).Methods:A total of 517 patients with OHE and HBC treated between January 2008 and July 2018 were enrolled.Patients were divided into the FZHY(n=129)and control groups(n=388),and the 6-month survival rates were compared between the two groups.Propensity score matching(PSM)was used to reduce the bias caused by confounding factors.Results:In multivariable regression analysis,FZHY therapy was an independent protective factor of 6-month survival.After PSM(1:2),the FZHY and control group comprised 126 and 252 patients,respectively.The 6-month survival rate was remarkably higher in the FZHY group than in the control group(P<0.005).FZHY users,especially those with a model for end-stage liver disease score>20 and Child-Pugh class C,benefited significantly from FZHY therapy.Conclusions:Adjuvant therapy with FZHY may be associated with improved survival in patients with OHE and HBC.However,further clinical studies are required to validate our findings.

Fuzheng Huayu Capsule(扶正化瘀胶囊)in the Treatment of Liver Fibrosis:Clinical Evidence and Mechanism of Action

Liver fibrosis represents the wound healing response to liver injury from a wide variety of etiologies. Remarkable progresses have been shown in the field of liver fibrosis in a range of areas in the past years. In particular, the reversibility of liver fibrosis has been well documented in both patients and animal models. Great progresses have been made in the treatment of liver fibrosis with Chinese medicine. This review summarizes the effects of Fuzheng Huayu Capsule （扶正化瘀胶囊, FZHYC） in treating liver fibrosis and inflammation induced by chronic hepatitis B in clinical trials and the mechanism of action of FZHYC in reversing liver fibrosis in vivo and in vitro experiments.