Chemical Genomic Profiling Unveils the in Vitro and in Vivo Antiplasmodial Mechanism of Aa (Euterpe oleracea Mart.) Polyphenols. Academic Article uri icon

abstract

  • 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 ("aa") originates from Brazil and has anti-inflammatory and antineoplasic properties. Here, we evaluated the antimalarial efficacy of three phenolic fractions of aa; 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 chemical genomic profiling (HIP) utilizing heterozygous Saccharomyces cerevisiae deletion mutants to identify molecular mechanisms of aa fractions. HIP results indicate proteostasis as the main cellular pathway affected by fraction 2. These results open avenues to develop aa polyphenols as potential new antimalarial candidates.

published proceedings

  • ACS Omega

author list (cited authors)

  • Ferreira, L. T., Venancio, V. P., Kawano, T., Abro, L., Tavella, T. A., Almeida, L. D., ... Costa, F

complete list of authors

  • Ferreira, Letícia T||Venancio, Vinícius P||Kawano, Taila||Abrão, Lailah CC||Tavella, Tatyana A||Almeida, Ludimila D||Pires, Gabriel S||Bilsland, Elizabeth||Sunnerhagen, Per||Azevedo, Luciana||Talcott, Stephen T||Mertens-Talcott, Susanne U||Costa, Fabio TM

publication date

  • September 2019