Abstract
BackgroundCerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, thus, alternative therapies are increasingly necessary. In this study, the effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice.MethodsC57BL/6 mice were pre-treated with aqueous extract or fractions of A. blazei, or chloroquine, infected with P. berghei ANKA and then followed by daily administration of A. blazei or chloroquine. Parasitaemia, body weight, survival and clinical signs of the disease were evaluated periodically. The concentration of pro-and anti-inflammatory cytokines, histopathology and in vitro analyses were performed.ResultsMice treated with A. blazei aqueous extract or fraction C, that shows antioxidant activity, displayed lower parasitaemia, increased survival, reduced weight loss and protection against the development of CM. The administration of A. blazei resulted in reduced levels of TNF, IL-1β and IL-6 production when compared to untreated P. berghei-infected mice. Agaricus blazei (aqueous extract or fraction C) treated infected mice displayed reduction of brain lesions. Although chloroquine treatment reduced parasitaemia, there was increased production of proinflammatory cytokines and damage in the CNS not observed with A. blazei treatment. Moreover, the in vitro pretreatment of infected erythrocytes followed by in vivo infection resulted in lower parasitaemia, increased survival, and little evidence of clinical signs of disease.ConclusionsThis study strongly suggests that the administration of A. blazei (aqueous extract or fraction C) was effective in improving the consequences of CM in mice and may provide novel therapeutic strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0832-y) contains supplementary material, which is available to authorized users.
Highlights
Cerebral malaria (CM) is debilitating and sometimes fatal
We demonstrated that A. blazei and chloroquine administration decreased parasitaemia, increased survival, but A. blazei demonstrated greater protection against brain damage when compared with chloroquine
Administration of Agaricus blazei aqueous extract decreases parasitaemia and increases survival of Plasmodium berghei‐infected mice Agaricus blazei aqueous extract-treated mice (100 mg/ Kg) displayed a significant decline in parasitaemia when compared with untreated mice at 6 and 7 dpi (Fig. 2a)
Summary
Cerebral malaria (CM) is debilitating and sometimes fatal. Disease severity has been associated with poor treatment access, therapeutic complexity and drug resistance and, alternative therapies are increasingly necessary. The effect of the administration of Agaricus blazei, a mushroom of Brazilian origin in a model of CM caused by Plasmodium berghei, strain ANKA, was investigated in mice. The most debilitating phenotype of severe malaria is a neurological syndrome known as cerebral malaria (CM) [22,23,24], which predominantly affects children in sub-Saharan Africa. This disease has a mortality rate around 20 % and is accompanied by seizures and neurocognitive dysfunction [21, 25]. As noted successful antimalarial therapy is effective in eliminating the parasite from the bloodstream, but does not prevent the development of neuronal damage [26, 28, 29]
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