Integrating network pharmacology, bioinformatics, and experimental validation to unveil the molecular targets and mechanisms of galangin to treat hepatocellular carcinoma

Abstract

Abstract Background Galangin, a flavonoid compound, is derived from Alpinia officinarum Hance. Previous studies have shown that galangin can inhibit the proliferation of hepatocellular carcinoma (HCC), but its mechanism is still unclear. This study aims to investigate the potential targets and molecular mechanisms of galangin on HCC through network pharmacology, bioinformatics, molecular docking, and experimental in vitro validation. Methods In this study, network pharmacology was investigated firstly to determine the targets and mechanisms of galangin in the treatment of HCC. AutoDockTools software was used to further simulate and calculate the binding of galangin to core targets.GO and KEGG enrichment analyses were conducted in the DAVID database to explore the main biological functions and signaling pathways impacted by galangin intervention. Moreover, bioinformatics was used to analyze the correlation between the differential expressions of galangin's anti-HCC core targets and the survival of HCC patients. Finally, the findings obtained from network pharmacology and bioinformatics were verified in cell experiments. Results A total of 67 overlapping target genes of galangin and HCC were identified. Through the PPI network analysis, 10 hub genes with the highest degree of freedom, including SRC, ESR1, MMP9, CDK4, CCNB1, MMP2, CDK2, CDK1, CHEK1, and PLK1, were screened and found to be closely related to the decomposition of the extracellular matrix, signal transduction, and the cell cycle, etc. GO and KEGG enrichment analyses revealed that galangin exerts an anti-HCC role by affecting various signaling pathways, including the cell cycle, pathways in cancer, and the PI3K-Akt signaling pathway, etc. Molecular docking demonstrated that CCNB1, CDK4, CDK1, and PLK1 had a powerful bond with galangin. Bioinformatics revealed that CCNB1, CDK4, CDK1, and PLK1 were up-regulated in the livers of patients with HCC at both mRNA and protein levels. The in vitro experiment showed that galangin can induce apoptosis of HepG2 and Huh7 cells and inhibit the proliferation of HCC cell. Conclusions Galangin induces apoptosis in HCC cells by blocking the cell cycle at the G0/G1 or G2/M phase through the inhibition of cyclins or mRNA expression.