Investigation of Antiparasitic Activity of Two Marine Natural Products, Estradiol Benzoate, and Octyl Gallate, on Toxoplasma gondii In Vitro

Abstract

Toxoplasmosis, caused by Toxoplasma gondii, is a common disease worldwide and could be severe and even fatal in immunocompromised individuals and fetuses. Limitation in current available treatment options drives the need to develop novel therapeutics. This study assessed the anti-T. gondii potential of 103 marine natural products. A luminescence-based β-galactosidase activity assay was used to screen the marine natural products library. Afterward, those compounds that displayed over 70% parasite inhibition ratio were further chosen to assess their cytotoxicity. Compounds exhibiting low cytotoxicity (≥80% cell viability) were applied to evaluate the inhibition efficacy on discrete steps of the T. gondii lytic cycle, including invasion, intracellular growth, and egress abilities as well as the cell cycle. We found that both estradiol benzoate and octyl gallate caused >70% inhibition of tachyzoite growth with IC50 values of 4.41 ± 0.94 and 5.66 ± 0.35 μM, respectively, and displayed low cytotoxicity with TD50 values of 34.11 ± 2.86 and 26.4 ± 0.98 μM, respectively. Despite their defects in inhibition of invasion and egress of tachyzoite, the two compounds markedly inhibited the tachyzoite intracellular replication. Flow cytometric analyses further suggested that the anti-T. gondii activity of estradiol benzoate, rather than octyl gallate, may be linked to halting cell cycle progression of tachyzoite from G1 to S phase. Taken together, these findings suggest that both estradiol benzoate and octyl gallate are potential inhibitors for anti-T. gondii infection and support the further exploration of marine natural products as a thinkable source of alternative and active agents against T. gondii.

The In Vitro Anti-Parasitic Activities of Emodin toward Toxoplasma gondii

“…Toxoplasmosis, which currently affects nearly one-third of humans, is caused by Toxoplasma gondii , an intracellular, obligate parasite with a low host specificity [ 3 , 4 ]. In healthy individuals, Toxoplasma infection may go unnoticed, but in immunocompromised or pregnant individuals, it may result in morbidity and mortality [ 5 ]. Consuming tissue cysts (which contain the bradyzoite form) in undercooked meat or oocysts (which contain the sporozoite form) discharged in felid fecal material can lead to host infection [ 6 ].…”

“…The relatively inactive tissue cysts can result in recurrent infections, especially in people who have compromised immune systems. Sulfadiazine and/or pyrimethamine are the currently available therapeutic options for toxoplasmosis, but these medications have poor effectiveness and the tolerance for them is low [ 5 ]. Furthermore, the available treatments do not eliminate tissue cysts.…”