Chronic inflammation involves dysregulation in the synthesis of pro-inflammatory mediators which are associated with several diseases. Some natural plant products are known to possess anti-inflammatory properties based on their high content of antioxidants. In this study, we demonstrate that ethanol extract of whole dried sugarcane (WDS EE) is a potent source of polyphenols, flavonoids and antioxidants with high free-radical scavenging activity. In vitro studies performed in a cellular model of intestinal inflammation using LPS-stimulated SW480 colon cancer cells show that WDS EE supresses the phosphorylation of the NFκB transcription factor, concomitantly reducing protein expression and secretion of the IL-8 chemokine.
Mass spectrometry based phosphoproteomics enabled comparison of WDS EE with the well-known plant polyphenol, resveratrol (RSV), which demonstrated both overlapping and independent cellular responses. For WDS EE we observed the deactivation of inflammatory-modulators PKA, PKC, EGFR and c-Jun. Kinase enrichment analysis and subsequent inhibitory studies confirmed a key role of CRAF kinase in mediating WDS EE activity. Further studies using SWATH-MS quantitated 2944 proteins across all samples and subsequent bioinformatics predicted that WDS EE down-regulates NFκB pathway members including TLR2, TLR4, NIK, IκBα, and iNOS, while RSV has its key activity through members of the PI3K pathway. Overall, our findings show that WDS is a source of polyphenols that acts differently to RSV and reduces some mediators of inflammation in epithelial cells.