1. Copaifera spp. oleoresins and two isolated compounds (ent-kaurenoic and ent-polyalthic acid) inhibit Toxoplasma gondii growth in vitro.
- Author
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Teixeira SC, de Souza G, Junior JPL, Rosini AM, Martínez AFF, Fernandes TAM, Ambrósio SR, Veneziani RCS, Bastos JK, Martins CHG, Barbosa BF, and Ferro EAV
- Subjects
- HeLa Cells, Humans, Reactive Oxygen Species metabolism, Cytokines metabolism, Interleukin-6 metabolism, Molecular Docking Simulation, Diterpenes pharmacology, Diterpenes isolation & purification, Diterpenes chemistry, Toxoplasma drug effects, Toxoplasma growth & development, Fabaceae chemistry, Plant Extracts pharmacology, Plant Extracts chemistry, Plant Extracts isolation & purification
- Abstract
Toxoplasmosis affects about one-third of the world's population. The disease treatment methods pose several side effects and do not efficiently eliminate the parasite, making the search for new therapeutic approaches necessary. We aimed to assess the anti-Toxoplasma gondii activity of four Copaifera oleoresins (ORs) and two isolated diterpene acids, named ent-kaurenoic and ent-polyalthic acid. We used HeLa cells as an experimental model of toxoplasmosis. Uninfected and infected HeLa cells were submitted to the treatments, and the parasite intracellular proliferation, cytokine levels and ROS production were measured. Also, tachyzoites were pre-treated and the parasite invasion was determined. Finally, an in silico analysis was performed to identify potential parasite targets. Our data show that the non-cytotoxic concentrations of ORs and diterpene acids controlled the invasion and proliferation of T. gondii in HeLa cells, thus highlighting the possible direct action on parasites. In addition, some compounds tested controlled parasite proliferation in an irreversible manner. An additional and non-exclusive mechanism of action involves the modulation of host cell components, by affecting the upregulation of the IL-6. Additionally, molecular docking suggested that ent-polyalthic acid has a high affinity for the active site of the TgCDPK1 protein. Copaifera ORs have great antiparasitic activity against T. gondii, and this effect can be partially explained by the presence of the isolated compounds ent-kaurenoic and ent-polyalthic acid., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)
- Published
- 2024
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