Exploring the Anti-Inflammatory Potential of a Steroid from Antarctic Lichen Umbilicaria antarctica (L.) Ach.: In Vitro, In Vivo Zebrafish Assay, and In Silico Studies

Chemical analysis of the Antarctic lichen Umbilicaria antarctica (L.) Ach. led to the isolation of four compounds (1–4). Among these, 9,11-dehydroergosterol peroxide (3) demonstrated the most substantial anti-inflammatory effects both in vitro and in vivo using zebrafish models. Molecular docking studies were conducted to assess the binding affinities of the selected compounds with important inflammatory mediators iNOS and IL-10, and molecular dynamics (MD) simulations were performed on the most potent anti-inflammatory compound. RMSD plot analysis indicated that 3 remained stable throughout a 200 ns simulation period, particularly with iNOS. RMSF plots also suggested a stable and well-fitted conformation of 3 within the binding site of iNOS. The complex stability during the simulation is attributable to the hydrophobic interactions of 3 with TRP463, which contributed over 40% to the protein-ligand interactions. These findings suggest that 9,11-dehydroergosterol peroxide (3) could be a promising new strategy for treating inflammation.