摘要
The most common medications for the treatment of zoonotic toxoplasmosis are pyrimethamine and sulfadiazine,which may cause serious undesirable side effects.Thus,there is an urgent need to develop novel therapeutics.Baicalein(BAI,C_(15)H_(10)O_(5))has been shown to perform well against protozoan parasites including Leishmania and Cryptosporidium.In this study,the inhibition efficacy of BAI on Toxoplasma gondii was evaluated using plaque,invasion,and intracellular proliferation assays.BAI effectively inhibited T.gondii(half-maximum inhibitory concentration(IC_(50))=6.457×10^(−5)mol/L),with a reduced invasion rate(33.56%)and intracellular proliferation,and exhibited low cytotoxicity(half-maximum toxicity concentration(TC_(50))=5.929×10^(−4)mol/L).Further investigation using a mouse model shed light on the inhibitory efficacy of BAI against T.gondii,as well as the potential mechanisms underlying its anti-parasitic effects.The survival time of T.gondii-infected ICR mice treated with BAI was remarkably extended,and their parasite burdens in the liver and spleen were greatly reduced compared with those of the negative control group.Histopathological examination of live sections revealed effective therapeutic outcomes in the treatment groups,with no notable pathological alterations observed.Furthermore,alterations in cytokine levels indicated that BAI not only effectively suppressed the growth of T.gondii but also prevented excessive inflammation in mice.Collectively,these findings underscore the significant inhibitory efficacy of BAI against T.gondii,positioning it as a promising alternative therapeutic agent for toxoplasmosis.
基金
supported by the National Natural Science Foundation of China(No.32370997)
the Key Projects Jointly Constructed by the Ministry and the Province of Zhejiang Medical and Health Science and Technology Project(No.WKJ-ZJ-2545)
the Chinese Medicine Science and Technology Program of Zhejiang Province(No.2024ZL367)
the Health Commission of Zhejiang Province(No.2024KY923)
the Foundation of GuoTai(Taizhou)Center of Technology Innovation for Veterinary Biologicals(No.GTKF(23)001),China.
