A multimodality therapeutic application on Toxoplasma gondii encephalitis utilizing Spiramycin and 'de novo' Ferula asafetida in immunodeficient mice.

Abstract

This study investigated a 'de Novo' medicinal herb, Ferula asafetida (FA), against toxoplasma encephalitis either alone or combined with spiramycin (SP). Female Swiss-Webster mice (n&#x2009;=&#x2009;72) were divided into three batches. Batch-I received no DMS to serve as an immunocompetent control, batch-II was immune-suppressed with the DMS (0.25&#x2009;mg/g/day) for 14&#x2009;days pre-infection, whilst batch-III was immune-suppressed with the DMS on the same day of infection. All experimental mice were inoculated with Toxoplasma gondii ME49 cysts (n&#x2009;=&#x2009;75). Each batch was split into four subgroups: Mono-SP, mono-FA, combined drug (SP&#x2009;+&#x2009;FA), or neither. Therapies were administered on day zero of infection in batches (I and II) and 35&#x2009;days post-infection in batch (III). Treatments lasted for 14&#x2009;days, and mice were sacrificed 60&#x2009;days post-infection. Histopathological changes, cysts load, and CD4 and CD8 T-cells were counted in brain tissues. The cyst-load count in mice receiving SP&#x2009;+&#x2009;FA was significantly (p&#x2009;<&#x2009;.0001) the least compared to the mono treatments in all protocols. Interestingly, the combined therapy demolished the T-cell subsets to zero in immunocompetent and immunocompromised infected mice. In conclusion, F. asafetida might be a powerfully natural, safe vehicle of SP in the digestive system and/or across the brain-blood barrier to control toxoplasmosis even through immunodeficient conditions.