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The Sesquiterpene Lactone, Budlein A, Inhibits Antigen-Induced Arthritis in Mice: Role of NF-κB and Cytokines.
Zarpelon, Ana C; Fattori, Victor; Souto, Fabricio O; Pinto, Larissa G; Pinho-Ribeiro, Felipe A; Ruiz-Miyazawa, Kenji W; Turato, Walter M; Cunha, Thiago M; da Costa, Fernando B; Cunha, Fernando Q; Casagrande, Rubia; Arakawa, Nilton S; Verri, Waldiceu A.
Afiliação
  • Zarpelon AC; Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, Londrina, Parana, 86051-990, Brazil.
  • Fattori V; Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, Londrina, Parana, 86051-990, Brazil.
  • Souto FO; Department of Pharmacology, Ribeirão Preto Medical School, Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • Pinto LG; Department of Pharmacology, Ribeirão Preto Medical School, Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • Pinho-Ribeiro FA; Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, Londrina, Parana, 86051-990, Brazil.
  • Ruiz-Miyazawa KW; Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, Londrina, Parana, 86051-990, Brazil.
  • Turato WM; Department of Pharmacology, Ribeirão Preto Medical School, Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • Cunha TM; Department of Pharmacology, Ribeirão Preto Medical School, Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • da Costa FB; Department of Pharmaceutical Sciences, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • Cunha FQ; Department of Pharmacology, Ribeirão Preto Medical School, Preto, University of São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo, 14049-900, Brazil.
  • Casagrande R; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Londrina, Paraná, 86038-350, Brazil.
  • Arakawa NS; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Londrina, Paraná, 86038-350, Brazil.
  • Verri WA; Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid PR 445, Km 380 Cx. Postal 10.011, Londrina, Parana, 86051-990, Brazil. waldiceujr@yahoo.com.br.
Inflammation ; 40(6): 2020-2032, 2017 12.
Article em En | MEDLINE | ID: mdl-28780730
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by debilitating pain, cartilage destruction, and loss of joint function. Management of RA includes drugs that target NF-κB and downstream cytokine production. Therefore, molecules that act by inhibiting this signaling pathway without the severe side effects of, for instance, corticoids would be suitable therapeutic strategies. Budlein A is a sesquiterpene lactone with antinociceptive and anti-inflammatory properties related to the inhibition of pro-inflammatory cytokines and neutrophil recruitment. In this study, the effect of budlein A was evaluated in antigen-induced arthritis (AIA) in mice. At the 26th day, leukocyte recruitment to the knee joint, knee contents of proteoglycans, blood levels of ALT and AST, stomach tissue myeloperoxidase activity, and RT-qPCR for pro-inflammatory gene mRNA expression in knee joint samples was performed. NF-κB luciferase activity was evaluated in RAW 264.7 macrophages. Budlein A treatment dose-dependently inhibited AIA-induced mechanical hyperalgesia, edema, total leukocytes and neutrophil recruitment, and proteoglycan degradation. Budlein A did not induce gastric or liver damage. Budlein also inhibited AIA-induced Il-33, Tnf, Il-1ß, preproET-1, and Cox-2 mRNA expression. In vitro, budlein reduced TNF- and IL-1ß-induced NF-κB activity in RAW 264.7 macrophages. Altogether, we demonstrate that budlein A ameliorates AIA-induced inflammation and pain by targeting NF-κB. Importantly, budlein A does not induce in vivo side effects, suggesting that it possesses a favorable pre-clinical profile as analgesic and it is a prosperous molecule to be further investigated for the treatment of RA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Experimental / Sesquiterpenos / Lactonas Limite: Animals Idioma: En Revista: Inflammation Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artrite Experimental / Sesquiterpenos / Lactonas Limite: Animals Idioma: En Revista: Inflammation Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos