Antimalarial Activity of Methyl Gallate and Palmatine Combination in the Presence of Piperine

Abstract Artemisinin combination therapies have been recommended as first-line antimalarials in malaria endemic countries. However, treatment failures are already being reported in some countries. This has necessitated the search for novel compounds for combination therapy. Methyl gallate and palmatine have been reported to exhibit antiplasmodial activities but the antimalarial activity of their combination has not been evaluated. Therefore, the evaluation of the combination of methyl gallate and palmatine for antimalarial activity in vitro and in vivo in the presence of piperine was carried out. The inhibitory potential of methyl gallate and palmatine combination on β-hematin formation was studied in vitro. Also, the antimalarial activity of methyl gallate and palmatine combination with/without a bioenhancer (piperine) was evaluated in Plasmodium berghei NK65 infected mice. The results of β-hematin formation inhibition revealed that methyl gallate and palmatine in the ratio 3:2 had the highest inhibitory effect (IC50 = 0.73 µg/mL), the compounds acting synergistically. The 3:2 combination of methyl gallate and palmatine exhibited no antimalarial activity in the absence of piperine but caused reduction in parasitemia that exceeded 30% in the presence of piperine at the dose of 25 mg/kg body weight on day 4 post-inoculation. These suggest that 3:2 combination of methyl gallate and palmatine in the presence of piperine exhibited antimalarial activity, with the compounds synergistically inhibiting β-hematin formation.