Chemical Genomic Profiling Unveils the in Vitro and in Vivo Antiplasmodial Mechanism of Acai (Euterpe oleracea Mart.) Polyphenols

Autor(es):Mostrar menos -

Ferreira, Leticia T. ^[1] ; Venancio, Vinicius P. ^[2] ; Kawano, Taila ^{[2, 3]} ; Abrao, Lailah C. C. ^{[2, 3]} ; Tavella, Tatyana A. ^[1] ; Almeida, Ludimila D. ^[4] ; Pires, Gabriel S. ^[4] ; Bilsland, Elizabeth ^[4] ; Sunnerhagen, Per ^[5] ; Azevedo, Luciana ^[6] ; Talcott, Stephen T. ^[2] ; Mertens-Talcott, Susanne U. ^[2] ; Costa, Fabio T. M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Lab Trop Dis Prof Dr Luiz Jacintho da Silva, Dept Genet Evolut Microbiol & Immunol, BR-13083970 Campinas, SP - Brazil

^[2] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX 77843 - USA

^[3] Univ Fed Alfenas, Fac Pharmaceut Sci, BR-37130001 Alfenas, MG - Brazil

^[4] Univ Campinas UNICAMP, Synthet Biol Lab, Dept Struct & Funct Biol, Inst Biol, BR-13083970 Campinas, SP - Brazil

^[5] Univ Gothenburg, Dept Chem & Mol Biol, SE-40530 Gothenburg - Sweden

^[6] Univ Fed Alfenas, Lab Nutr & Toxicol Anal Vivo LANTIN, Fac Nutr, Alfenas, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ACS OMEGA; v. 4, n. 13, p. 15628-15635, SEP 24 2019.
• Citações Web of Science: 0

Resumo

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 ({''}acai{''}) originates from Brazil and has anti-inflammatory and antineoplasic properties. Here, we evaluated the antimalarial efficacy of three phenolic fractions of acai; 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 acai fractions. HIP results indicate proteostasis as the main cellular pathway affected by fraction 2. These results open avenues to develop acai polyphenols as potential new antimalarial candidates. (AU)

• Processo FAPESP: 15/03553-6 - Engenharia genética de leveduras para a descoberta de novos medicamentos
• Beneficiário: Elizabeth Bilsland
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 17/01986-8 - Determinação da especificidade ao substrato de transportadores da membrana plasmática de Saccharomyces cerevisiae e de Homo sapiens
• Beneficiário: Ludimila Dias Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/18611-7 - Desenvolvimento de novas ferramentas para busca e validação de alvos moleculares para terapia contra Plasmodium vivax
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/50400-6 - Advancing academic partnership in the discovery of anti malarial microbial metabolites of botanicals
• Beneficiário: Fabio Trindade Maranhão Costa
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07007-4 - Identificação de novos tratamentos antimaláricos através de uma abordagem de "reposicionamento de fármacos" centrada no alvo
• Beneficiário: Elizabeth Bilsland
• Modalidade de apoio: Auxílio à Pesquisa - Regular