Methyl-Haematommate and lobaric-acid

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-κB activation and the secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in LPS-stimulated macrophages. Inhibition and docking simulation experiments provided evidence that lobaric acid and pseudodepsidones bind to PPAR-γ between helix H3 and the beta sheet, similarly to partial PPAR-γ agonists. These findings suggest that lobaric acid and pseudodepsidones reduce the expression of pro-inflammatory cytokines by blocking the NF-κB pathway via the activation of PPAR-γ.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Depsides; Dose-Response Relationship, Drug; Humans; Lactones; Lichens; Lipopolysaccharides; Macrophages; Molecular Docking Simulation; Molecular Structure; NF-kappa B; PPAR gamma; Salicylates; Signal Transduction; Structure-Activity Relationship; U937 Cells

Seven phenolic lichen metabolites (1-7) have been isolated from a methanol extract of the Antarctic lichen Stereocaulon alpinum by various chromatographic methods. The structures of these compounds were determined mainly by analysis of NMR spectroscopic data. A depsidone-type compound, lobaric acid (1) and two pseudodepsidone-type compounds, 2 and 3, exhibited potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B) with IC(50) values of 0.87microM, 6.86microM, and 2.48microM, respectively. Kinetic analyses of PTP1B inhibition by compounds 1 and 2 suggested that these compounds inhibited PTP1B activity in a non-competitive manner.

Topics: Depsides; Enzyme Inhibitors; Kinetics; Lactones; Lichens; Plant Extracts; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Salicylates