Fig. 1

Transcriptional changes associated with phloretin treatment of macrophages. RNA sequencing was performed to establish the anti-inflammatory effects of phloretin and identify the underlying mechanisms. Differentially expressed genes were used as input for the core analysis in ingenuity pathway analysis (IPA) (n = 5, cut-off criteria p < 0.05, see supplementary Fig. 1). A Pathway analysis showing down- and upregulated canonical pathways of phloretin-stimulated macrophages treated with or without LPS respectively. -Log (P-value of overlap) and down- or upregulated canonical pathways with corresponding z-score are indicated at x- and y-axis, respectively. B, C Heat map representing the normalized counts of differentially expressed genes associated to the pro-inflammatory canonical pathways (iNOS-, toll-like receptor-, acute phase response- and interferon-signaling) and the Nrf2 pathway. A colour gradient was used to indicate the normalized counts and corresponding fold change (Fc) differences per sample and gene, respectively. D Upstream analysis showing down- and upregulated transcription regulators of phloretin-stimulated macrophages treated with or without LPS respectively. E Downstream analysis of the RNA-seq samples in IPA illustrated that phloretin upregulated the expression of a set of genes involved in the regulation of ROS levels as one of the main downstream functional effects (z-score: 2.008). Ctrl, control; phl, phloretin; Fc, Fold change