Allan J C Bussmann1, Sergio M Borghi1, Tiago H Zaninelli1, Telma S Dos Santos1, Carla F S Guazelli1, Victor Fattori1, Talita P Domiciano1, Felipe A Pinho-Ribeiro1, Kenji W Ruiz-Miyazawa1, Antonio M B Casella2, Josiane A Vignoli3, Doumit Camilios-Neto3, Rubia Casagrande4, Waldiceu A Verri5. 1. Department of Pathology, Biological Science Center, Londrina State University, Rod. Celso Garcia Cid, PR 445, Km 380, Londrina, Paraná State, 86051-990, Brazil. 2. Department of Clinical Medicine, Health Science Center, Londrina State University, University Hospital, 86039-440, Londrina, Paraná State, Brazil. 3. Department of Biochemistry and Biotechnology, Exact Sciences Center, Londrina State University, Londrina, 86057-970, Brazil. 4. Department of Pharmaceutical Sciences, Health Science Center, Londrina State University, University Hospital, Londrina, Paraná State, 86039-440, Brazil. 5. Department of Pathology, Biological Science Center, Londrina State University, Rod. Celso Garcia Cid, PR 445, Km 380, Londrina, Paraná State, 86051-990, Brazil. waverri@uel.br.
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.
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.
Authors: Victor Fattori; Karla G G Serafim; Ana C Zarpelon; Sergio M Borghi; Felipe A Pinho-Ribeiro; José C Alves-Filho; Thiago M Cunha; Fernando Q Cunha; Rúbia Casagrande; Waldiceu A Verri Journal: J Drug Target Date: 2016-10-24 Impact factor: 5.121
Authors: Camila R Ferraz; Thacyana T Carvalho; Marília F Manchope; Nayara A Artero; Fernanda S Rasquel-Oliveira; Victor Fattori; Rubia Casagrande; Waldiceu A Verri Journal: Molecules Date: 2020-02-10 Impact factor: 4.411