The Sesquiterpene Lactone, Budlein A, Inhibits Antigen-Induced Arthritis in Mice: Role of NF-kappa B and Cytokines

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Zarpelon, Ana C. ^[1] ; Fattori, Victor ^[1] ; Souto, Fabricio O. ^[2] ; Pinto, Larissa G. ^[2] ; Pinho-Ribeiro, Felipe A. ^[1] ; Ruiz-Miyazawa, Kenji W. ^[1] ; Turato, Walter M. ^[2] ; Cunha, Thiago M. ^[2] ; da Costa, Fernando B. ^[3] ; Cunha, Fernando Q. ^[2] ; Casagrande, Rubia ^[4] ; Arakawa, Nilton S. ^[4] ; Verri, Jr., Waldiceu A. ^{[1, 5]}

Afiliação do(s) autor(es)

^[1] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Ciencias Patol, Rod Celso Garcia Cid PR 445, Km 380, BR-86051990 Londrina, Parana - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Pharmaceut Sci, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[4] Univ Estadual Londrina, Ctr Ciencias Saude, Dept Ciencias Farmaceut, BR-86038350 Londrina, Parana - Brazil

^[5] Univ Estadual Londrina, Ctr Ciencias Biol, Dept Patol, Rod Celso Garcia Cid Pr 445, KM 380, BR-86057970 Londrina, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Inflammation; v. 40, n. 6, p. 2020-2032, DEC 2017.
• Citações Web of Science: 6

Resumo

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-kappa B 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-kappa B 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-1 beta, preproET-1, and Cox-2 mRNA expression. In vitro, budlein reduced TNF- and IL-1 beta-induced NF-kappa B activity in RAW 264.7 macrophages. Altogether, we demonstrate that budlein A ameliorates AIA-induced inflammation and pain by targeting NF-kappa B. 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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Linha de fomento: Auxílio à Pesquisa - Temático