The Role of Metfirnin and Artesunate-amodiaquine Combination in Preventing Cerebral Malaria in Mice

Background and objective: Cerebral malaria is one of the important complications of malaria infection responsible for most malaria-related cases of death. This study investigated the antiplasmodial and some neurological effect of metformin prophylaxis and artesunate-amodiaquine curative regimen in Plasmodium berghei infected male mice.
Methods: Sixty male mice were randomly divided into six groups labeled I to VI with each group containing ten mice. Group I was normal control (NC) that received water and feed ad libitum, group II was negative control parasitized with P. berghei berghei and not treated, while group III wast positive control parasitized and treated with artesunate-amodiaquine. Group IV received metformin prophylaxis for seven days before pasitemia induction and not treated thereafter. Group V received metformin for seven days, parasitized and later treated with artesunate-amodiaquine. Group VI were treated with metformin and artesunate-amodiaquine combination after parasitemia induction. Initial parasitemia was established after 72 hours using tail-blood film microscopy, and final parasitemia was determined 24 hours after the last treatment. All post-infection treatments lasted for three days, after which the animals were euthanized. The hippocampal tissues were harvested, and some homogenized and the homogenate used for biochemical assay; while some others were used histological examination.
Results: Parasitemia level was significantly (p < 0.05) decreased in treated groups, especially in the group that received both metformin prophylaxis and artesunate-amodiaquine post-infection treatment (group V). The oxidative stress biomarkers, inflammatory biomarkers and neurotransmitters in the hippocampal homogenates of treated groups especially group V were significantly (p < 0.05) restored close to those of normal mice.
Conclusions: This study concludes that metformin could be repurposed as a good prophylactic agent to artemisinin-based combination therapies against Plasmodium malaria infection. This implies that metformin prophylaxis might help in combating Plasmodial malaria resistance; thus, prevent complications such as cerebral malaria.

Metformin, Artesunate-amodiaquine, P.berghei, Cerebral malaria, Neurotransmitters

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