Lobaric acid and pseudodepsidones inhibit NF-kappa B signaling pathway by activation of PPAR-gamma

Herein we report the anti-inflammatory activity of lobaric acid and pseudodepsidones isolated from the nordic lichen Stereocaulon paschale. Lobaric acid (1) and three compounds (2, 7 and 9) were found to inhibit the NF-kappa B activation and the secretion of pro-inflammatory cytokines (IL-1 beta and TNF-alpha) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-gamma between helix H3 and the beta sheet, similarly to partial PPAR-gamma agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-kappa B pathway via the activation of PPAR-gamma.