Evaluation of Experimental Cerebral Malaria of Curcumin and Kaempferol in Plasmodium berghei ANKA-Infected Mice

Abstract

Background: Cerebral malaria (CM) is one of the most severe complications of Plasmodium falciparum infection and the leading cause of death from malaria in endemic areas. Natural products with antioxidant and anti-inflammatory activities have become valuable alternative therapeutic options in CM treatment. Therefore, this study aimed to investigate the neuroprotective effects of curcumin and kaempferol in experimental cerebral malaria (ECM) in mice infected with Plasmodium berghei ANKA (PbA). Methods: After PbA infection, mice were divided into 9 groups, namely Group I (negative control (NC)) with 0.5% HPMC, Group II received chloroquine 20 mg/kg, Group III (normal) with aquadest, Groups IV, V, and VI received curcumin at doses of 20, 40, and 80 mg/kg, respectively, Groups VII, VIII, and IX received kaempferol at doses of 20, 40, and 80 mg/kg, respectively. The antimalarial activity was evaluated using Peter's four-day suppressive test. This was conducted to determine the % parasitemia, survival rate, AST and ALT, blood-brain barrier (BBB) leakage, and neurobehavioral disorders in mice with CM. Results: The results showed that all treatments had significant antimalarial activity, with the % suppression depending on the dose. It also indicates that PbA-infected mice had a survival rate of 11-19 days after infection, which was higher than those in the NC group. This suggested that curcumin and kaempferol have a protective effect on the survival of PbA-infected mice. Furthermore, they significantly reduced the AST and ALT concentrations in the sample compared to the NC group. The same was observed in cerebral vessel extravasation, where the Evans Blue stain assay showed significantly less dye extravasation in the brains of PbA-infected mice treated with curcumin and kaempferol. This indicated better-protected integrity of the BBB. Additionally, the results also demonstrated a decrease in neurological disorders arising during ECM in the group treated with curcumin and kaempferol. Conclusion: Considering these results, it is concluded that treatments with curcumin and kaempferol could improve animal survival, prevent AST and ALT elevations, as well as protect the BBB and neurobehavioral disorders associated with CM in PbA-infected mice.