Hypericum perforatum extract and hyperforin inhibit the growth of neurotropic parasite Toxoplasma gondii and infection-induced inflammatory responses of glial cells in vitro

Hypericum perforatum L. has been widely used as a natural antidepressant. However, it is unknown whether it is effective in treating infection-induced neuropsychiatric disorders. In order to evaluate the effectiveness of H. perforatum against infection with neurotropic parasite Toxoplasma gondii, which has been linked to neuropsychiatric disorders, this study investigated the anti-Toxoplasma activity using in vitro models. Dried alcoholic extracts were prepared from three Hypericum species: H. perforatum, H. erectum, and H. ascyron. H. perforatum extract was further separated by solvent-partitioning. Hyperforin and hypericin levels in the extracts and fractions were analyzed by high resolution LC-MS. Anti-Toxoplasma activities were tested in vitro, using cell lines (Vero and Raw264), murine primary mixed glia, and primary neuron-glia. Toxoplasma proliferation and stage conversion were analyzed by qPCR. Infection-induced damages to the host cells were analyzed by Sulforhodamine B cytotoxicity assay (Vero) and immunofluorescent microscopy (neurons). Infection-induced inflammatory responses in glial cells were analysed by qPCR and immunofluorescent microscopy. Hyperforin was identified only in H. perforatum among the three tested species, whereas hypericin was present in H. perforatum and H. erectum. H. perforatum extract and hyperforin-enriched fraction, as well as hyperforin, exhibited significant anti-Toxoplasma property as well as inhibitory activity against infection-induced inflammatory responses in glial cells. In addition, H. perforatum-derived hyperforin-enriched fraction restored neuro-supportive environment in mixed neuron-glia culture. H. perforatum and its major constituent hyperforin are promising anti-Toxoplasma agents that could potentially protect neurons and glial cells against infection-induced damages. Further study is warranted to establish in vivo efficacy. [Display omitted]