Piperine Enhances the Antimalarial Activity of Curcumin in Plasmodium berghei ANKA-Infected Mice: A Novel Approach for Malaria Prophylaxis

Abstract

Malaria is a prevalent vector-borne infectious disease in tropical regions, particularly in the absence of effective vaccines and because of the emergence resistance of Plasmodium to available antimalarial drugs. An alternative strategy for malaria eradication could be the combination of existing compounds that possess antimalarial activity to target multiple stages of the parasite. This study evaluated the antimalarial activity of a combination of curcumin and piperine in mice. A total of 42 mice were assigned to six groups depending on the treatment administered: group I (normal group) with aquadest; group II (negative control) with 0.2 ml DMSO; group III received a standard malarial drug (artesunate 5 mg/kg BW); groups IV, V, and VI with curcumin 300 mg/kg BW, curcumin 300 mg/kg BW and piperine 20 mg/kg BW, and piperine 20 mg/kg BW, respectively. The antimalarial activity was evaluated using prophylactic assays in Plasmodium berghei ANKA-infected mice, including the percentage parasitemia, clinical signs, survival rate, serum biochemical analysis, parasitic load in the liver, and liver histopathology. All treatments showed significant ( $p<0.05$ ) antiplasmodial activity, with considerable parasite inhibition (>50%), curcumin 300 mg/kg BW (60.22%), curcumin 300 mg/kg BW, and piperine 20 mg/kg BW (77.94%) except for piperine 20 mg/kg BW (47.20%), eliciting greater inhibition relative to that of artesunate (51.18%). The delayed onset of clinical symptoms and prolonged survival rate were also significant ( $p<0.05$ ) in the combination of curcumin and piperine treated group. In addition, the low parasitic load in the liver and mild histopathological changes in the liver suggest that the combination of curcumin and piperine had synergistic or additive effects. These findings demonstrate the promising use of these combined compounds as a malarial prophylactic. Further studies were recommended to assess their clinical usefulness.