Discovery and Anti-inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway

We discovered a cyanobacterial fatty acid that contains an α,β-unsaturated carbonyl system a key motif required for the activation of the Keap1/Nrf2−ARE pathway that is involved in the activation of antioxidant and phase II detoxification enzymes. The compound was screened in ARE luciferase reporter gene assay which induced Nrf2 activity at 32 and 10µM. Given the established crosstalk between oxidative stress and inflammation, we aimed at investigating the antiinflammatory potential of our compound using RAW264.7 mouse macrophage. We carried RNAseq to capture the effects of the comound on transript levels and identify additional pathways invloved in inflammation that could be modulated. RAW264.7 mouse macrophage cells were treated with three concentrations (32, 10, 3.2 µM) of the fatty acid in addition to solvent control (DMSO) for 1h followed by stimulation with Lipopolysaccharide (LPS). The RNA was collected after 12h. RNA from cells treated with DMSO without LPS stimulation were also obtained.