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A new insight into purinergic pharmacology: Three fungal species as natural P2X7R antagonists.

Authors
  • Soares-Bezerra, Rômulo José1
  • da Silva Ferreira, Natiele Carla1
  • de Almeida Alves, Tânia Maria2
  • Zani, Carlos Leomar2
  • Rosa, Luiz Henrique3
  • Faria, Robson Xavier4
  • da Silva Frutuoso, Válber5
  • Alves, Luiz Anastacio1
  • 1 Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. , (Brazil)
  • 2 Laboratory of Chemistry of Bioactive Natural Products, René Rachou Research Center, Oswaldo Cruz Foundation, Belo Horizonte, Brazil. , (Brazil)
  • 3 Laboratory of Polar Microbiology and Tropical Connections, Federal University of Minas Gerais, Belo Horizonte, Brazil. , (Brazil)
  • 4 Laboratory of Toxoplasmosis and other Protozoosis, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. , (Brazil)
  • 5 Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. , (Brazil)
Type
Published Article
Journal
Phytotherapy Research
Publisher
Wiley (John Wiley & Sons)
Publication Date
Sep 01, 2019
Volume
33
Issue
9
Pages
2319–2328
Identifiers
DOI: 10.1002/ptr.6412
PMID: 31264271
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

P2X7 is a purinergic receptor involved in important physiological functions and pathological processes, such as inflammation, neurodegeneration, and pain. Despite its relevance, there is no selective antagonist useful in the treatment of diseases related to this receptor. In this context, research for a selective, safe, and potent antagonist compound that can be used in clinical therapy has been growing. In this work, we evaluated the potential antagonistic activity of three fungal extracts, namely, Vishniacozyma victoriae, Metschnikowia australis, and Ascomycota sp., which were discovered in a high-throughput screening campaign to search for new antagonists for P2X7R from natural products. First, the IC50 values of these fungal extracts were determined in J774.G8 (murine macrophage cell line) and U937 (human monocyte cell line) cells through dye uptake assays. The IC50 values of V. victoriae were 2.6 and 0.92 μg/mL, M. australis has IC50 values of 3.8 and 1.5 μg/mL, and Ascomycota sp. showed values of 2.1 and 0.67 μg/mL in J774.G8 and U937 cells, respectively. These extracts also significantly inhibited propidium iodide and Lucifer yellow uptake via P2X7R pore, P2X7R currents in electrophysiology, IL-1β release, and the production of oxide nitric and reactive oxygen species. The extracts did not cause cytotoxicity within a period of 24 h. The results showed the promising antagonistic activity of these extracts toward P2X7R, thereby indicating that they can be future candidates for phytomedicines with potential clinical applicability.

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