Exploring The Active Mechanism Of Berberine Against HCC By Systematic Pharmacology And Molecular Docking

ObjectiveTo study the pharmacological effect of berberine on hepatocellular carcinoma and its molecular mechanism based on systematic pharmacology and molecular docking.MethodsA systematic pharmacological approach and a computer molecular docking approach were used to predict the potential mechanism of action of berberine(BBR)against hepatocellular carcinoma from two aspects:gene ontology(GO)and signaling pathways.Through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database and PharmMapper database to retrieve Berberine(BBR)to predict the target of BBR,and use UniProt database to query the target protein corresponding the name of the gene,and finally the target protein regulated by BBR.Hepatocellular carcinoma-related genes were retrieved through OncoDB.HCC and Liverom databases.The BBR target protein and hepatocellular carcinoma-related genes are mapped,and the mapped genes are used to construct a protein interaction(PPI)network through the interaction database String.DAVID database was used to perform gene function annotation and pathway enrichment analysis on the mapped genes to further explore the specific action mechanism of BBR against hepatocellular carcinoma.Based on the results of systematic pharmacological analysis,the inhibitory effect of BBR on hepatocellular carcinoma and its underlying mechanism were verified by in vitro experiments.The effects of BBR on the proliferation and cell viability of liver cancer cells were examined.Flow cytometry was used to detect the effect of BBR on apoptosis of liver cancer cells.The effects of BBR on the migration and invasion ability of liver cancer cells were detected by scratch and chamber experiments.Western blotting was used to detect apoptosis-related proteins and the effects of PI3K/AKT signaling pathways.Using the computer molecular docking method,the software AutoDock4.2 was used to dock the BBR and AKT to evaluate their binding ability and possible inhibitory effect.ResultsThrough systematic pharmacological analysis,it was found that BBR plays an important role in inhibiting liver cancer by affecting multiple pathways,especially the PI3K/AKT signaling pathway.This study investigated the inhibitory effect of BBR on the PI3K/AKT pathway of liver cancer,and determined that BBR down-regulated the expression of phosphorylated AKT and PI3K in MHCC97-H and HepG2 cells,and inhibited their growth,cell migration and Invasion.In addition,the inhibitory effect of BBR on the AKT pathway also caused apoptosis in MHCC97-H and HepG2 cells.The molecular docking results also indicate that the combination of BBR and AKT can lead to inhibition of AKT activity.ConclusionThis study uses systematic pharmacology combined with molecular docking methods and in vitro experiments to verify that BBR has a significant inhibitory effect on the growth and metastasis of liver cancer cells and its molecular mechanism.