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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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]
Total Authors: 13
[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
Total Affiliations: 5
Document type: Journal article
Source: Inflammation; v. 40, n. 6, p. 2020-2032, DEC 2017.
Web of Science Citations: 6

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)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support type: Research Projects - Thematic Grants