Therapeutic Antitoxoplasmosis Potential of Garcinia cambogia: Evidence From In Silico and In Vivo Studies.

Toxoplasma gondii, an opportunistic protozoan, is widely prevalent and poses potential health risks. Its treatment remains challenging with several side effects, urging the exploration of new, safe, and efficient drugs. We aimed to explore the therapeutic efficacy of the medicinal plant Garcinia cambogia (GC) against both acute and chronic toxoplasmosis. Sixty Swiss albino mice were allocated into five groups: I (healthy), II (model), III (spiramycin [SPM] treated, IV (GC treated), and V (SPM + GC treated). Each group is further divided into two subgroups receiving treatment at 4 and 42 days postinfection (dpi) for acute and chronic infection, respectively. To determine the properties of the GC active compounds, hydroxycitric acid (HCA), guttiferone-E, guttiferone-J, compared to SPM against the selective T. gondii ROP18 transferase target regarding its binding affinities, and estimated inhibition constant, Lipinski's RO5 filter analyses and computational QSARs/ADMET predictive characteristics were used. The groups were evaluated parasitologically, histopathologically, and immunohistochemically for Iba-1 expression. The best treatment outcome was observed in the SPM + GC-treated groups in both acute and chronic infections, with inhibition percentages of 89% and 78%, respectively, and preservation of neuronal integrity, as evidenced by the lowest Iba1 expression levels. Moreover, the docked ROP18-HCA revealed an additional, critical, and novel ligand-binding site for ROP18, which is essential for the virulence and pathogenesis of Toxoplasma. G. cambogia's stability of intermolecular binding activities, potency, and conformations makes it an effective, safe, and promising remedy for treating toxoplasmosis, especially in combination with SPM.