Marcos Herraiz, SaraIrisarri Gutiérrez, Maria JoseCarrión, JavierAzami Conesa, IrisSuárez Lombao, RodrigoNavarro Rocha, JulianaQuílez, Jose FranciscoFernández Barrero, AlejandroOchoa, EnekoGonzález Coloma, AzucenaGómez Muñoz, María TeresaBailén, María2025-11-072025-11-072025-10-03Marcos-Herraiz, S., Irisarri-Gutiérrez, M. J., Carrión, J., Conesa, I. A., Lombao, R. S., Navarro-Rocha, J., Quilez, J. F., Barrero, A. F., Larrigan, E. O., González-Coloma, A., Muñoz, M. T. G., & Bailén, M. (2025). Activity of Geranium macrorrhizum extracts, essential oils and their main components against three relevant flagellated protozoa (p. 2025.10.03.680318). bioRxiv. https://doi.org/10.1101/2025.10.03.6803182692-8205https://hdl.handle.net/10532/7956Plant-derived natural products are structurally diverse secondary metabolites that play essential ecological roles and have long been recognized for their therapeutic potential. Geranium macrorrhizum is known to produce bioactive extracts and essential oils rich in monoterpenoids and sesquiterpenes. While various Geranium species have demonstrated antiprotozoal activity, the potential of G. macrorrhizum against protozoan parasites remains unexplored. Given the increasing resistance of protozoan pathogens to conventional treatments, there is a pressing need to identify alternative therapeutic agents from natural sources. Plant material was grown in greenhouse and aeroponic systems. Extracts were obtained via hydrodistillation and Soxhlet, and analyzed by GC-MS. In vitro assays were performed to evaluate antiparasitic activity and cytotoxicity. Morphological changes induced by germacrone were analyzed using light microscopy. The study evaluated the antiparasitic potential of essential oils, extracts, and compounds from Geranium macrorrhizum, cultivated under controlled conditions, against Giardia duodenalis, Trichomonas gallinae, and Leishmania infantum. Results showed broad-spectrum activity, particularly from non-polar extracts and EOs, suggesting that lipophilic compounds, especially germacrone, are key contributors to the observed effects. Germacrone exhibited strong activity and selective toxicity. Structural analogues of germacrone showed reduced efficacy, highlighting the importance of its specific chemical structure. Morphological analyses revealed parasite-specific responses to germacrone, contrasting with the more destructive effects of metronidazole and amphotericin B. The findings support G. macrorrhizum as a promising source of natural antiprotozoal agents and justify further investigation into its bioactive compounds and mechanisms of action.enAttribution-NonCommercial-NoDerivs 3.0 Spaintexto2025-10-0710.1101/2025.10.03.680318TrichomonasGiardiaLeishmaniaEsencia (aceite esencial)Metabolito secundarioSalud y bienestarProducción y consumo responsablesVida de ecosistemas terrestres