Study on the Mechanism of Plantago asiatica L.in the treatment of liver cancer based on network pharmacology,molecular docking and in vitro experiments
Objective To explore the active components,key targets and potential molecular mechanisms of Plantago asiatica L.in the treatment of liver cancer by network pharmacology combined with molecular docking and in vitro experiment verification.Methods The main active components and potential targets of P.asiatica L.were obtained from TCMSP and Swiss Target Prediction databases,and a"component-target"network was constructed.The liver cancer-related disease targets were obtained from DisGeNET and GeneCards databases,and the PPI network analysis of the intersection targets was performed by String database combined with Cytoscape software.The GO and KEGG enrichment analysis was performed by DAVID database,and the main active components of P.asiatica L.were selected for molecular docking verification with the core targets.Furthermore,the anti-tumor activity of the active components of P.asiatica L.was verified through in vitro Hep3B cell experiments.The proliferation inhibition effect was detected by CCK-8 experiment,and the tumor formation ability was detected by plate colony formation experiment and soft agar colony formation experiment.The AKT activity level was detected by K-LISA AKT activity kit,and the mRNA expression was detected by qRT-PCR.Results The core active components of P.asiatica L.included melampyroside,6-OH-luteolin,stigmasterol,baicalin,stigmasteryl palmitate,sitosterol,luteolin,baicalein,dinatin,β-sitosteryl palmitate.168 intersection genes between P.asiatica L.and liver cancer were obtained,and the PPI network showed that the intersection genes were closely related,and the potential targets were AKT1,TNF,ESR1,EGFR,etc.316 GO functions and 94 related pathways were obtained by enrichment analysis,and the related pathways mainly included PI3K-AKT signaling pathway,etc..Molecular docking results showed that the main active component luteolin bound stalely with the core target(AKT1,EGFR,TNF,ESR1,SRC,MAPK3).In vitro experiment results showed that luteolin had inhibitory effects on the proliferation of liver cancer cells,luteolin could interfere with the clonal formation of liver cancer cells and reduce the activity of AKT signaling pathway,and the mRNA expression of apoptosis-related genes such as BCL2 and FASL was increased.Conclusion P.asiatica L.can treat liver cancer by multiple targets and multiple pathways,and its main active component is luteolin.Luteolin may act on key targets such as AKT1 and inhibit PI3K-AKT signaling pathway,thereby inhibiting the proliferation of liver cancer cells and promoting the apoptosis of liver cancer cells,which has potential anti-liver cancer activity.
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