Abstract

Lichens are an important source of diverse and unique secondary metabolites with recognized biological activities through experimental and computational procedures. The objective of this study is to investigate the metabolomic profile of the ethanolic extract of the Antarctic lichen Gondwania regalis and evaluate its antioxidant and antidiabetic activities with in vitro, in silico, and molecular dynamics simulations. Twenty-one compounds were tentatively identified for the first time using UHPLC/ESI/QToF/MS in negative mode. For antioxidant activity, the DPPH assay showed an IC50 value of 2246.149 mu g/mL; the total phenolic content was 31.9 mg GAE/g, the ORAC assay was 13.463 mu mol Trolox/g, and the FRAP assay revealed 6.802 mu mol Trolox/g. Regarding antidiabetic activity, enzyme inhibition yielded IC50 values of 326.4513 mu g/mL for pancreatic lipase, 19.49 mu g/mL for alpha-glucosidase, and 585.216 mu g/mL for alpha-amylase. Molecular docking identified sekikaic acid as the most promising compound, with strong binding affinities to catalytic sites, while molecular dynamics confirmed its stability and interactions. Toxicological and pharmacokinetic analyses supported its drug-like potential without significant risks. These findings suggest that the ethanolic extract of Gondwania regalis is a promising source of bioactive compounds for developing natural antioxidant and antidiabetic therapies.