Rottlerin impairs early and late steps of Toxoplasma gondii infection in human trophoblast cells and villous explants

• Published in: Chemico-biological interactions 2023-10, Vol.384, p.110716-110716, Article 110716
• Main Authors: Teixeira, Samuel Cota, Paschoalino, Marina, de Souza, Guilherme, Rosini, Alessandra Monteiro, de Lima Junior, Joed Pires, Luz, Luana Carvalho, Fajardo Martínez, Aryani Felixa, Alves, Rosiane Nascimento, Almeida, Marcos Paulo Oliveira, Damasceno, Jaqueline Lopes, Silva, Marcelo José Barbosa, Ietta, Francesca, Barbosa, Bellisa Freitas, Ferro, Eloisa Amália Vieira, Gomes Martins, Carlos Henrique
• Format: Article
• Language: English
• Subjects: Congenital toxoplasmosis; Maternal-fetal interface; Natural compounds; Rottlerin; Toxoplasma gondii; Trophoblast
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2023.110716

Congenital toxoplasmosis, caused by the opportunistic protozoan parasite T. gondii, can cause stillbirths, miscarriages and fetal abnormalities, as well as encephalitis and chorioretinitis in newborns. Available treatment options rely on antiparasitic drugs that have been linked to serious side effects, high toxicity and the development of drug-resistant parasites. The search for alternative therapeutics to treat this disease without acute toxicity for the mother and child is essential for the advancement of current therapeutic procedures. The present study aimed to unravel the mode of the anti-T. gondii action of Rottlerin, a natural polyphenol with multiple pharmacological properties described. Herein, we further assessed the antiparasitic activity of Rottlerin against T. gondii infection on the human trophoblastic cells (BeWo cells) and, for the first time, on human villous explants. We found that non-cytotoxic doses of Rottlerin impaired early and late steps of parasite infection with an irreversible manner in BeWo cells. Rottlerin caused parasite cell cycle arrest in G1 phase and compromised the ability of tachyzoites to infect new cells, thus highlighting the possible direct action on parasites. An additional and non-exclusive mechanism of action of Rottlerin involves the modulation of host cell components, by affecting lipid droplet formation, mitochondrial function and upregulation of the IL-6 and MIF levels in BeWo cells. Supporting our findings, Rottlerin also controlled T. gondii proliferation in villous explants with low toxicity and reduced the IL-10 levels, a cytokine associated with parasite susceptibility. Collectively, our results highlighted the potential use of Rottlerin as a promising tool to prevent and/or treat congenital toxoplasmosis. •Rottlerin controls T. gondii infection in human trophoblast cells and villous explants.•Rottlerin strongly inhibits T. gondii proliferation with an irreversible manner.•Rottlerin caused parasite cell cycle arrest in G1 phase.•Rottlerin treatment upregulates IL-6 and MIF levels in BeWo cells.•Rottlerin is able to affect lipid droplet formation and mitochondrial function.