Lichen-Derived Bioactive Compounds in Diabetes and Cardiovascular Risk: Experimental Evidence, Mechanisms, and Translational Challenges.

Cardiometabolic disorders arise from interconnected metabolic, inflammatory, oxidative, mitochondrial, and vascular abnormalities. Lichens produce structurally diverse secondary metabolites, including depsides, depsidones, dibenzofurans, anthraquinones, and other phenolic compounds, whose experimental activities intersect several of these pathways. This narrative review examines the chemical diversity, biological actions, and translational potential of lichen-derived compounds in diabetes and cardiovascular risk modulation. Available studies describe antioxidant, anti-inflammatory, enzyme-inhibitory, antiglycation, cytoprotective, and vasomodulatory effects, but the evidence is predominantly based on chemical assays, molecular docking, in vitro experiments, and heterogeneous preclinical models. Direct demonstrations of improved insulin sensitivity, pancreatic β-cell function, endothelial function, lipid handling, or atherosclerosis remain limited, and human efficacy data are lacking. Translation is further constrained by incomplete chemical standardisation, uncertain bioavailability and target-tissue exposure, limited interaction data, and safety concerns. Usnic acid illustrates the central challenge: broad biological activity coexists with mitochondrial toxicity and clinically relevant hepatotoxic potential. Lichen metabolites therefore currently represent pharmacological probes and medicinal-chemistry scaffolds rather than clinically applicable interventions for diabetes or cardiovascular risk reduction. Future development requires compound-specific target validation, reproducible preparations, pharmacokinetic characterisation, functional disease endpoints, and rigorous safety assessment.