Puerariae Flos promotes apoptosis through the ESR1-ERK1/2 signaling pathway to intervene in alcoholic hepatocellular carcinoma

Abstract Ethnopharmacological relevance: Increasing evidence indicates that conventional traditional Chinese medicine (TCM) plays a cardinal role in oncological remedies. Initially, our research group focused on research related to the sobering-up and liver-protecting effects of Gehua jiecheng fang, and found that these plants also have anticancer properties. Among these pathogens, Puerariae Flos (PF) is the main component of the fungus, and there is also literature supporting the use of PF for HCC care. Aim of the study: PF is utilized to treat tumors in China. However, its effect on and mechanism involved in alcohol-associated hepatocellular carcinoma (alcohol-related HCC) remain elusive. This investigation aimed to address this knowledge gap through experiments and bioinformatics. Materials and methods: Limid chromatography-tandem mass spectrometry (LC‒MS/MS) was used as an initial method for identifying chemical compounds that were present in the drug sera. The prognostic DEGs were determined using univariate Cox regression analysis. The diagnostic value of the DEGs was estimated by constructing survival curves and utilizing the curved TCGA and GEO datasets, which are connected to alcoholic HCC according to their recipient operation characteristics (ROC). The affinity and stability between the target and predictive chemical compounds were checked by means of molecular docking and molecular dynamics simulations. Furthermore, the selected genes were subjected to clinical correlation analysis and KEGG analysis. The impact of PF on migration and cell proliferation was evaluated via western blotting. Results: LC‒MS/MS revealed 68 components and identified 844 objects, 63 of which overlapped with the aims of patients with alcoholic HCC. Seven methods were used to determine that the ESR1 and CDK1 genes have advantages in the diagnosis of alcoholic HCC. Molecular docking and molecular dynamics demonstrated strong binding affinities between key components andESR1. Pathway analysis revealed that the two core genes were involved in apoptosis in a complex manner, with ESR1 showing enrichment in the chemogenic receptor activation pathway. The diagnostic significance of ESR1 was confirmed by Western blot and in vitro experiments. Conclusion: PF inhibits the migration and proliferation of alcohol-related HCC cells by regulating the ESR1/ERK1/2 pathway to promote cell apoptosis.