Bioaccessibility, anti-Helicobacter pylori activity and immunomodulatory effects of Hypogymnia physodes (L.) Nyl. extract: in vitro assessment of potential food-related applications

Abstract Lichens are a promising but insufficiently explored source of bioactive secondary metabolites. This study aimed to characterize Hypogymnia physodes (L.) Nyl. extract and evaluate, under in vitro conditions, its anti- Helicobacter pylori and urease-inhibitory activity, immunomodulatory effects, gastrointestinal bioaccessibility, food-matrix interactions, and effects on selected lactic-acid bacteria. The extract was dominated by physodic acid (32%), physodalic acid (23%), 3-hydroxyphysodic acid (17%), and atranorin (11%). It inhibited tested H. pylori strains, including isolates with different antibiotic-resistance phenotypes, with MIC values of 31.25–125 mg/L, and inhibited urease with an IC₅₀ of 14.45 mg/L. In LPS-stimulated THP-1-derived macrophages, the extract reduced NO and ROS levels, COX-2 protein levels, and phagocytosis, while cell viability remained largely unaffected up to 75 µg/mL. Simulated gastrointestinal digestion showed limited, metabolite-dependent soluble bioaccessibility; food matrices, particularly protein-rich ones, markedly affected metabolite recovery. Relative protein digestibility decreased by up to 25%, whereas starch digestibility was unaffected. The digested extract did not inhibit the nine tested lactic-acid bacterial strains. Overall, these in vitro findings support further investigation, but toxicological, microbiome, mechanistic, and in vivo studies are required before functional-food applications can be established.