TY - JOUR
T1 - The citrus flavanone naringenin attenuates zymosan-induced mouse joint inflammation
T2 - induction of Nrf2 expression in recruited CD45+ hematopoietic cells
AU - Bussmann, Allan J.C.
AU - Borghi, Sergio M.
AU - Zaninelli, Tiago H.
AU - dos Santos, Telma S.
AU - Guazelli, Carla F.S.
AU - Fattori, Victor
AU - Domiciano, Talita P.
AU - Pinho-Ribeiro, Felipe A.
AU - Ruiz-Miyazawa, Kenji W.
AU - Casella, Antonio M.B.
AU - Vignoli, Josiane A.
AU - Camilios-Neto, Doumit
AU - Casagrande, Rubia
AU - Verri, Waldiceu A.
N1 - Funding Information:
Funding This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenacão de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Ministé-rio da Ciência Tecnologia e Inovação (MCTI), Secretaria da Ciência, Tecnologia e Ensino Superior (SETI), Fundação Araucária, and Paraná State Government, Brazil. Sergio M. Borghi received a postdoctoral fellowship from CAPES and CNPq (152792/2016-3). The authors also thank the support of Central Multiusuário de Laboratórios de Pesquisa da Universidade Estadual de Londrina (CMLP-UEL).
Publisher Copyright:
© 2019, Springer Nature Switzerland AG.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
KW - Arthritis
KW - Inflammation
KW - Naringenin
KW - NFκB
KW - Nrf2
KW - Pain
KW - Zymosan
UR - http://www.scopus.com/inward/record.url?scp=85059582395&partnerID=8YFLogxK
U2 - 10.1007/s10787-018-00561-6
DO - 10.1007/s10787-018-00561-6
M3 - Article
C2 - 30612217
AN - SCOPUS:85059582395
SN - 0925-4692
VL - 27
SP - 1229
EP - 1242
JO - Inflammopharmacology
JF - Inflammopharmacology
IS - 6
ER -