From Traditional Sources to Pharmacological Innovation: Discovery, Safety, and Therapeutic Potential of Natural Compounds

Natural products continue to play a central role in drug discovery, with many modern therapeutics originating from bioactive compounds found in plants, fungi, and propolis. These sources provide structurally diverse secondary metabolites such as flavonoids, alkaloids, terpenoids, and phenolic derivatives, that remain essential reservoirs for pharmacologically relevant chemical scaffolds. Integrating advances in metabolomics, computational drug design, and mechanistic pharmacology has made it possible to more effectively translate natural compounds into credible therapeutic candidates.This topic focuses on the translational pharmacology of natural products derived specifically from plants, fungi, and propolis, emphasizing the journey from the identification of bioactive compounds to the demonstration of therapeutic potential. We encourage submissions that explore the discovery and characterisation of active metabolites, their molecular targets and signaling pathways, and the biological relevance of their pharmacological actions.Consideration will be given to research that links chemical characterisation, structure–activity relationships (SAR), biological validation, and safety or toxicological assessment. Approaches integrating in vitro, in vivo, and in silico methods are encouraged, especially where they provide mechanistic insight or support the potential development of natural compounds into well-defined therapeutic agents. Studies incorporating ethnopharmacological knowledge and connecting traditional uses with experimentally verified pharmacological outcomes are also highly valued.We especially welcome contributions that:- Isolate, identify, and characterize bioactive metabolites from plants, fungi, or propolis with complete documentation of source materials.- Clarify mechanisms of action, including molecular targets or pathway modulation.- Develop structure–activity relationships (SAR) to explain potency or functional behaviour.- Assess safety and toxicity, including cytotoxicity, off-target effects, or dose–response outcomes.- Integrate ethnopharmacological knowledge with experimental evidence to validate traditional uses.- Demonstrate translational relevance, highlighting robust biological effects and preclinical potential.The aim of this collection is to highlight how natural products from plants, fungi, and propolis can progress from traditional or initial discovery toward meaningful therapeutic innovation, supported by rigorous mechanistic science, safety evaluation, and biological validation.We welcome Original Research, Review, Mini-Review, and Perspective articles. All submissions must follow the Four Pillars of Best Practice in Ethnopharmacology and the ConPhyMP statement (Front. Pharmacol., 13:953205). Detailed documentation of plant or fungal material, propolis source, extraction, and processing is mandatory; manuscripts lacking this information will be desk-rejected. Purely computational or network-only studies without experimental or ethnobotanical grounding fall outside the journal’s scope. Best-practice guidance: https://ga-online.org/best-practice Topic editors: Gardenia Militao, Paulo Michel Pinheiro Ferreira, José Roberto de Oliveira Ferreira, Frederico Gleber-Netto, Karina Miranda Santiago Source: https://www.frontiersin.org/research-topics/75655/from-traditional-sources-to-pharmacological-innovation-discovery-safety-and-therapeutic-potential-of-natural-compounds