Ubidercarenone Decelerates the Manifestation of Experimental Cerebral Malaria in C57BL/6J Mice by ameliorating the Host Inflammatory Response

Abstract

Cerebral Malaria (CM), a highly lethal form of severe malaria is known to cause inflammation that exacerbates pathology in the brain predominantly due to inflammatory immune response as a result of Plasmodium falciparum infection. There is limited progress in the development of new approaches for the treatment of CM. Therefore, in this study we investigated whether oral Ubidercarenone (Ubn) can regulate the induction of inflammatory immune response in experimental cerebral malaria (ECM). Three groups of mice were utilized for this study, one group of C57BL/6J mice was used as control; group two was only infected with Plasmodium berghei ANKA (PbA) and group three orally supplemented with 200mg/kg ubn followed by infection with PbA. Here we show that Ubn was able to protected majority of mice against ECM. Importantly, Ubn supplementation significantly hampered infiltration of inflammatory monocytes, T cells and cytotoxic granzyme B into the brain. Serum analysis showed a reduction in the levels of TNFα in Ubn administered mice. Furthermore, Ubn administration resulted in decreased expression of chemokine CCR2 in the brain, leading to reduced levels of activated pathogenic T cells. Notably, antiinflammatory cytokines IL-10 and IL-22 together with T-regulatory cells, which are associated with protection during ECM, were up-regulated in Ubn treated mice. These results demonstrates that Ubn can assuage PbA-mediated inflammatory responses usually witnesses during ECM.