Evaluation of the inhibitory effects and the mechanism of terpenoids on Toxoplasma gondii tachyzoites.

• Novel natural terpenoids have anti- Toxoplasma gondii effects. • Target compounds exhibit low cytotoxicity to macrophages. • Lindenane sesquiterpenoids reduce tachyzoite number by inducing apoptosis. • Two compounds promote intracellular tachyzoites elimination by synergistic action with macrophages. Currently, symptomatic toxoplasmosis is treated with a combination of sulfadiazine and pyrimethamine. However, significant adverse effects and drug resistance have been reported. Terpenoids are widely found in nature, with numerous studies demonstrating that they have effective inhibitory effects on a variety of parasites. In this study, we employed intermediates or derivatives of lindenane sesquiterpenoids to evaluate their intracellular and extracellular inhibitory effects on Toxoplasma gondii tachyzoites and their cytotoxicity on macrophages. We demonstrated that two of these target terpenoids could effectively reduce the number of extracellular tachyzoites, probably by inducing tachyzoite apoptosis through altering tachyzoites mitochondrial membrane potential and calcium homeostasis. In addition, the two target terpenoids were able to promote intracellular tachyzoites elimination, possibly by enhancing macrophage activities. Two derivatives of lindenane sesquiterpenoids with low cytotoxicity to macrophages demonstrated direct and indirect anti toxoplasma effects. [ABSTRACT FROM AUTHOR]