Myricetin Inhibits Toxoplasma gondii Growth, Alters Intracerebral Cyst Morphology, and Demonstrates Therapeutic Efficacy In Vivo

Toxoplasma gondii (T. gondi) is a widespread zoonotic parasite that poses a significant threat to global public health, yet effective therapeutic options remain limited. In this study, we found that the flavonoid compound myricetin (MYR) can significantly inhibit the proliferation of T. gondii. This effect is associated with the inhibition of dihydroorotase (TgDHO) activity in the de novo pyrimidine biosynthesis pathway, and this inhibition can be partially reversed by exogenous supplementation with uracil. Further studies revealed that MYR treatment can induce cell cycle arrest in tachyzoites and impair bradyzoite proliferation, concurrently disrupting the UDP-GlcNAc glycosylation of the cyst wall. In mouse models, MYR demonstrated significant efficacy, achieving an 80% survival rate in acute infection and inducing morphological abnormalities in intracerebral cysts during chronic infection. Collectively, these findings elucidate the anti-Toxoplasma activity and multifaceted mechanisms of MYR, providing valuable insights for developing novel therapeutics against toxoplasmosis.