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01-12-2019 | Arthritis | Original Article

The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45⁺ hematopoietic cells

Authors: Allan J. C. Bussmann, Sergio M. Borghi, Tiago H. Zaninelli, Telma S. dos Santos, Carla F. S. Guazelli, Victor Fattori, Talita P. Domiciano, Felipe A. Pinho-Ribeiro, Kenji W. Ruiz-Miyazawa, Antonio M. B. Casella, Josiane A. Vignoli, Doumit Camilios-Neto, Rubia Casagrande, Waldiceu A. Verri Jr.

Published in: Inflammopharmacology | Issue 6/2019

Abstract

Background

Naringenin is a biologically active analgesic, anti-inflammatory, and antioxidant flavonoid. Naringenin targets in inflammation-induced articular pain remain poorly explored.

Methods

The present study investigated the cellular and molecular mechanisms involved in the analgesic/anti-inflammatory effects of naringenin in zymosan-induced arthritis. Mice were pre-treated orally with naringenin (16.7–150 mg/kg), followed by intra-articular injection of zymosan. Articular mechanical hyperalgesia and oedema, leucocyte recruitment to synovial cavity, histopathology, expression/production of pro- and anti-inflammatory mediators and NFκB activation, inflammasome component expression, and oxidative stress were evaluated.

Results

Naringenin inhibited articular pain and oedema in a dose-dependent manner. The dose of 50 mg/kg inhibited leucocyte recruitment, histopathological alterations, NFκB activation, and NFκB-dependent pro-inflammatory cytokines (TNF-α, IL-1β, and IL-33), and preproET-1 mRNA expression, but increased anti-inflammatory IL-10. Naringenin also inhibited inflammasome upregulation (reduced Nlrp3, ASC, caspase-1, and pro-IL-1β mRNA expression) and oxidative stress (reduced gp91^phox mRNA expression and superoxide anion production, increased GSH levels, induced Nrf2 protein in CD45⁺ hematopoietic recruited cells, and induced Nrf2 and HO-1 mRNA expression).

Conclusions

Naringenin presents analgesic and anti-inflammatory effects in zymosan-induced arthritis by targeting its main physiopathological mechanisms. These data highlight this flavonoid as an interesting therapeutic compound to treat joint inflammation, deserving additional pre-clinical and clinical studies.

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Title: The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45+ hematopoietic cells
Authors: Allan J. C. Bussmann
Sergio M. Borghi
Tiago H. Zaninelli
Telma S. dos Santos
Carla F. S. Guazelli
Victor Fattori
Talita P. Domiciano
Felipe A. Pinho-Ribeiro
Kenji W. Ruiz-Miyazawa
Antonio M. B. Casella
Josiane A. Vignoli
Doumit Camilios-Neto
Rubia Casagrande
Waldiceu A. Verri Jr.
Publication date: 01-12-2019
Publisher: Springer International Publishing
Keyword: Arthritis
Published in: Inflammopharmacology / Issue 6/2019
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-00561-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation: induction of Nrf2 expression in recruited CD45⁺ hematopoietic cells

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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