Licochalcone A: An effective and low-toxicity compound against Toxoplasma gondii in vitro and in vivo

摘要

Toxoplasma gondii , an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti- T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vitro and in vivo . The safe concentration of Lico A in HFF cells was determined by MTT cell viability assays. The presence of T. gondii was assessed by qPCR and Giemsa staining. Azithromycin and sulfadiazine, commonly used effective treatments, served as drug controls. T. gondii ultrastructural alterations were observed by electron microscopy. The anti- T. gondii activity of Lico A was evaluated using an in vivo mouse infection model. In vitro , Lico A had no negative effect on host cell viability at concentrations below 9?μg/mL; however, it did inhibit T. gondii proliferation in a dose-dependent manner, with a 50% inhibitory concentration (IC₅₀) of 0.848?μg/mL. Electron microscopy analyses indicated substantial structural and ultrastructural changes in tachyzoites after Lico A treatment. Nile Red staining assays demonstrated that Lico A caused lipid accumulation. Lico A treatment significantly increased the survival rate of BALB/c mice infected with T. gondii . Lico A achieved the same therapeutic effect as a commonly used clinical drugs (combination of sulfadiazine, pyrimethamine and folinic acid). In conclusion, Lico A has strong anti- T. gondii activity in vitro and in vivo and might be developed into a new anti- T. gondii drug. Moreover, Lico A may exert these effects by interfering with lipid metabolism in the parasite.