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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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 gp91phox 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.

Original languageEnglish
Pages (from-to)1229-1242
Number of pages14
JournalInflammopharmacology
Volume27
Issue number6
DOIs
StatePublished - Dec 1 2019

Keywords

  • Arthritis
  • Inflammation
  • Naringenin
  • NFκB
  • Nrf2
  • Pain
  • Zymosan

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