From biodiversity to clinical translation: A global review of lichen-derived natural products and their pharmacological potential

Lichens, which are unique ecosystems formed by fungi and photosynthetic partners like algae or cyanobacteria, hold great potential for drug discovery. This review compiled four decades of research to create the first comprehensive global database of 14,230 lichen species, among which 116 were highlighted for proven medicinal properties. Our spatial analysis identified key regions for therapeutic potential, such as Europe, coastal North America, East Asia, and Oceania, with the Parmeliaceae family was found to contain the most bioactive species. We systematically described 82 lichen-derived metabolites with confirmed pharmacological effects. Depsidones show promise as agents against oxidative stress and cancer; depsides/polysaccharides demonstrate efficacy in modulating neuroinflammation and immune response; and terpenoids contribute to addressing antimicrobial resistance. Cytotoxic, anticancer, anti-tumor, anti-microbial, and antioxidant activities are associated with the largest number of medicinal species. This research bridges traditional knowledge of lichens with modern pharmacology, identifying 195 medicinal species that need further validation for clinical use. We also discussed challenges in translating this knowledge into practice, such as ensuring sustainable biomass, optimizing bioavailability, and ensuring clinical safety, and we suggested lichen-specific guidelines for these processes. As lichen metabolites offer compelling opportunities to tackle pressing global health issues, such as antimicrobial resistance, neurodegenerative disorders, and cancer, we advocate for lichen metabolites as promising solutions for future pharmaceutical development. • Presents a global database of 14,230 lichens, highlighting 116 medicinal species. • Identifies 82 lichen metabolites with confirmed pharmacological effects. • Discusses translational challenges like sustainable sourcing and bioavailability.