Glabridin exhibits potent inhibitory effects against Toxoplasma gondii in vitro and in vivo

BackgroundToxoplasma gondii is an obligate protozoan parasite capable of infecting a wide range of warm-blooded animals and humans. Current treatment options, primarily pyrimethamine and sulfadiazine, have limitations, such as high recurrence rates, long treatment durations, and limited effectiveness against T. gondii. There is an unmet need for novel, safe, low-toxicity, and highly effective treatments. This study aimed to evaluate the anti-T. gondii effects of glabridin, a natural compound derived from the roots of a widely used medicinal plant.MethodsThe cytotoxicity of glabridin in Vero cells was assessed using a CCK-8 cell viability assay. Quantitative polymerase chain reaction (qPCR) targeting the Tg-529 gene was developed to quantify T. gondii and assess the inhibitory effects of glabridin on parasite proliferation. Ultrastructural changes in T. gondii after treatment were examined using electron microscopy. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (Delta Psi m) were examined to assess the effects of glabridin on ROS levels and Delta Psi m in T. gondii tachyzoites. Additionally, metabolomics and transcriptomics analyses were conducted to investigate the mechanisms underlying glabridin's anti-T. gondii effects.ResultsGlabridin exhibited low toxicity to host cells and effectively inhibited T. gondii invasion and proliferation in vitro in a time-dependent manner. Glabridin-treated tachyzoites exhibited significant structural alterations, along with increased ROS production and a reduction in Delta Psi m. Metabolomic analysis indicated that glabridin significantly affected amino acid metabolism pathways in T. gondii. In vivo, glabridin treatment significantly improved survival rates in T. gondii-infected BALB/c mice at a dosage of 100 mg/kg.ConclusionsThis study demonstrates that glabridin has potent anti-T. gondii effects in vitro and in vivo, likely through disruption of amino acid metabolism in the parasite. These findings highlight glabridin's potential as a promising therapeutic agent for toxoplasmosis.