Suppressive effects of oroxylin A on intracellular proliferation ofToxoplasma gondiivia host cell ERK phosphorylation inhibition

Abstract

ABSTRACTToxoplasma gondiiposes a significant threat to immunocompromised patients, resulting in high mortality rates. Considering the side effects of anti-Toxoplasmadrugs, we focused on a potential candidate, oroxylin A (OA), a common component extracted fromAstragalus membranaceusandScutellaria baicalensiswhich suppressed the growth ofT. gondii in vitroandin vivo.Our result demonstrated that OA suppressedT. gondiiintracellular proliferation and downregulated phosphorylation of ERK1/2 ofT. gondii-infected host cells very similar to the MEK1 specific inhibitor PD98059. Ourin silicoanalysis showed that OA interacts sufficiently with the mammalian MEK1 region where established MEK1 inhibitors like PD98059 and trametinib bind. Moreover, OA improved the survival rate inT. gondii-infected mice. This study proposes that host MEK1 is a novel potential target for anti-Toxoplasmadrugs with a new mechanism of action.