Fig. 4

Juglone induced ferroptosis by targeting p38MAPK. A Venn diagram shows the intersection of juglone's drug gene targets and ferroptosis related targets. B The STRING database was used to analyze the interactions of 27 co-targets in A, and the entire network was identified and visualized through Cytosscape. (The color and size of circles represent the significant correlation and the degree of association, respectively. The larger the circle, the more number of enrichment, and the redder the color, the more significant the difference). C The key genes were verified using WB experiments. D GO and KEGG pathway enrichment analysis were performed on the 27 co-targets. E Volcano plot shows the distribution of differential expression genes between the control group and the juglone group through transcriptomics sequencing. F Heat map shows the intersection of significantly different genes obtained based on sequencing results and ferroptosis-related genes. G Using the STRING database to build a functional protein association network of predicted targets related to juglone, p38 and GPX4. H, I WB assay was used to detect Nrf2 and Keap1 protein expression levels with different concentrations of juglone. J After immunoprecipitation with anti-Nrf2 antibody, Nrf2 ubiquitylation were assayed by WB analysis. K The molecular docking was used to predict the interaction between Juglone and Keap1 and p38MAPK respectively. **p < 0.01; ***p < 0.001