Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/56324
Type: Artigo de Periódico
Title: Biochanin A Regulates Key Steps of Inflammation Resolution in a Model of Antigen-Induced Arthritis via GPR30/PKA-Dependent Mechanism
Authors: Franciel Batista Felix
Gabriel Henrique Campolina Silva
Frederico Marianetti Soriani
Lirlândia Pires Sousa
Renata Grespan
Mauro Martins Teixeira
Vanessa Pinho
Juliana Priscila Vago
Débora de Oliveira Fernandes
Débora Gonzaga Martins
Isabella Zaidan Moreira
Walyson Coelho Costa
Jessica Maria Dantas Araújo
Celso Martins Queiroz Junior
William Antonio Gonçalves
Abstract: BiochaninA(BCA)isanaturalorganiccompoundoftheclassofphytochemicalsknownas flavonoidsandisoflavonesubclasspredominantlyfoundinredclover(Trifoliumpratense).It has anti-inflammatory activity and some pro-resolving actions, such as neutrophil apoptosis. However, the effect of BCA in the resolution of inflammation is still poorly understood. In this study, we investigated the effects of BCA on the neutrophilic inflammatory response and its resolution in a model of antigen-induced arthritis. Male wild-type BALB/c mice were treated with BCA at the peak of the inflammatory process (12h). BCA decreased the accumulation of migrated neutrophils, and this effect was associated with reduction of myeloperoxidase activity, IL-1β and CXCL1 levels, and the histological score in periarticular tissues. Joint dysfunction, as seen by mechanical hypernociception, was improved by treatment with BCA. The resolution interval (Ri) was also quantified, defining profiles of acute inflammatory parameters that include the amplitude and duration of the inflammatory response monitored by the neutrophil infiltration. BCA treatment shortened Ri from ∼23h observed in vehicle-treated mice to ∼5.5h, associated with an increase in apoptotic events and efferocytosis, both key steps for the resolution of inflammation. These effects of BCA were prevented by H89, an inhibitor of protein kinase A (PKA) and G15, a selective G protein–coupled receptor 30 (GPR30)antagonist.Inlinewiththeinvivodata,BCAalsoincreasedtheefferocyticabilityof murine bone marrow–derived macrophages. Collectively, these data indicate for the first time that BCA resolves neutrophilic inflammation acting in key steps of the resolution of inflammation, requiring activation of GPR30 and via stimulation of cAMP-dependent signaling.
Subject: Artrite
Apoptose
Inflamação
language: por
metadata.dc.publisher.country: Brasil
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
metadata.dc.publisher.department: FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS
ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA
ICB - DEPARTAMENTO DE FARMACOLOGIA
ICB - DEPARTAMENTO DE MORFOLOGIA
Rights: Acesso Aberto
metadata.dc.identifier.doi: https://doi.org/10.3389/fphar.2021.662308
URI: http://hdl.handle.net/1843/56324
Issue Date: 2021
metadata.dc.url.externa: https://www.frontiersin.org/articles/10.3389/fphar.2021.662308/full
metadata.dc.relation.ispartof: Frontiers in Pharmacology
Appears in Collections:Artigo de Periódico



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