Evaluating the Antimalarial Potential of d-α-Tocopherol Polyethylene Glycol 1000 Succinate and α-Tocopherol, In Vivo Studies in Plasmodium berghei-Infected Mice and Molecular Docking Insights

Abstract

Oxidative stress is a pivotal factor in the pathogenesis of malaria, contributing to the development of conditions such as anemia, respiratory complications, and cerebral malaria. To counteract oxidative damage, we evaluated the effects of vitamin E (α-TOH) and d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) supplementation on parasitemia progression, mortality rate, and blood-brain barrier (BBB) permeability in Plasmodium berghei ANKA-infected mice. The mice were divided into four groups: a control group (untreated and uninfected), an infected group (Pb), a TPGS + Pb group, and an α-TOH + Pb group. The results demonstrated that TPGS was more effective than α-TOH, exhibiting a lower parasitemia (9.59%) and mortality (40%) by Day 12 and superior BBB protection in advanced infection stages. These findings suggest that TPGS may represent a promising therapeutic strategy for the management of malaria. Molecular docking analysis indicated that TPGS exhibited the highest binding affinity with plasmepsin 2 (−7.3 kcal/mol), whereas vitamin E demonstrated the strongest binding with plasmepsin 1 (−7.2 kcal/mol).