Chemical Genomic ProfilingUnveils the in Vitro andin Vivo Antiplasmodial Mechanism of Açaí (Euterpe oleracea Mart.) Polyphenols

摘要

Malaria remains a major detrimental parasitic disease in the developing world, with more than 200 million cases annually. Widespread drug-resistant parasite strains push for the development of novel antimalarial drugs. Plant-derived natural products are key sources of antimalarial molecules. Euterpe oleracea Martius (“açaí”) originates from Brazil and has anti-inflammatory and antineoplasic properties. Here, we evaluated the antimalarial efficacy of three phenolic fractions of açaí; total phenolics (>1), nonanthocyanin phenolics (>2), and total anthocyanins (>3). In vitro, fraction >2 moderately inhibited parasite growth in chloroquine-sensitive (HB3) and multiresistant (Dd2) Plasmodium falciparum strains, while none of the fractions was toxic to noncancer cells. Despite the limited activity in vitro, the oral treatment with 20 mg/kg of fraction >1 reduced parasitemia by 89.4% in Plasmodium chabaudi-infected mice and prolonged survival. Contrasting in vitro and in vivo activities of >1 suggest key antiplasmodial roles for polyphenol metabolites rather than the fraction itself. Finally, we performed haploinsufficiency chemicalgenomic profiling (HIP) utilizing heterozygous Saccharomycescerevisiae deletion mutants to identify molecularmechanisms of açaí fractions. HIP results indicateproteostasis as the main cellular pathway affected by fraction >2. These results open avenues to develop açaípolyphenols as potential new antimalarial candidates.