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

Artikel i vetenskaplig tidskrift
Författare Letícia T Ferreira
Vinícius P Venancio
Taila Kawano
Lailah C C Abrão
Tatyana A Tavella
Ludimila D Almeida
Gabriel S Pires
Elizabeth Bilsland
Per Sunnerhagen
Luciana Azevedo
Stephen T Talcott
Susanne U Mertens-Talcott
Fabio T M Costa
Publicerad i ACS Omega
Volym 4
Nummer/häfte 13
Sidor 15628-15635
ISSN 2470-1343
Publiceringsår 2019
Publicerad vid Institutionen för kemi och molekylärbiologi
Sidor 15628-15635
Språk en
Länkar dx.doi.org/10.1021/acsomega.9b02127
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Farmakognosi, Bioinformatik och systembiologi, Cellbiologi

Sammanfattning

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 chemical genomic profiling (HIP) utilizing heterozygous Saccharomyces cerevisiae deletion mutants to identify molecular mechanisms of açaí fractions. HIP results indicate proteostasis as the main cellular pathway affected by fraction 2. These results open avenues to develop açaí polyphenols as potential new antimalarial candidates.

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