Antiinflammatory evaluation of miricetin flavonoid on PMA-activated neutrophils

• Grant number: 17/05233-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2017
• Effective date (End): September 30, 2019
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Karina Alves de Toledo
• Grantee: Sarah Mendes
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated scholarship(s): 19/01681-8 - CARS microscopy analysis of the interaction of flavonoids (quercetin, rutin and myricetin) and neutrophil extracellular traps (NETs) on A549 cells, BE.EP.IC

Abstract

Myricetin is a flavonoid found in several foods, including those indicated as a supplement in the treatment of inflammatory diseases. During the inflammatory process, neutrophils are the first cells to be recruited because they are directly related to the activation and resolution of these events. Thus, often these cells are targeted for novel anti-inflammatory compounds. Neutrophils can be stimulated by different ligands that activate different signaling pathways, including those initiated by the phorbol esters such as PMA (phorbol myristate acetate), a potent neutrophil activator. Forbols specifically alter the signaling of protein kinase C in neutrophils, which are closely related to the production of reactive oxygen species (ROS) and therefore influent in important stages of neutrophil activity, such as adhesion, degranulation and NETs (Neutrophil Extracellular Traps) generation. Although myricetin is found in several plant extracts of known anti-inflammatory action, studies involving its action on neutrophils are still scarce. The objective of this work will be to analyze the anti-inflammatory activity of myricetin on PMA-activated neutrophils. For this purpose, we will analyze some important steps in the inflammatory process mediated by neutrophils: adhesion, degranulation and release of NETs. The in vitro assays will be complemented with in silica molecular docking analyzes with the intention of evaluating the interaction of myricetin with the enzymes myeloperoxidase and elastase that modulate the generation of NETs in an ERO-dependent manner. It is expected that the results obtained may aid in the broad understanding of the mechanisms by which myricetin and flavonoids are beneficial in the treatment of inflammatory diseases. (AU)