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Budlein A, a Sesquiterpene Lactone From Viguiera robusta, Alleviates Pain and Inflammation in a Model o Acute Gout Arthritis in Mice

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Fattori, Victor [1] ; Zarpelon, Ana C. [1] ; Staurengo-Ferrari, Larissa [1] ; Borghi, Sergio M. [1] ; Zaninelii, Tiago H. [1] ; Da Costa, Fernando B. [2] ; Aives, Jose C. [3] ; Cunha, Thiago M. [3] ; Cunha, Fernando Q. [3] ; Casagrande, Rubia [4] ; Arakawa, Nilton S. [4] ; Vern Jr, Waldiceu A.
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Estadual Londrina, Dept Pathol, Lab Pain Inflammat Neuropathy & Canc, Londrina - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, AsterBioChem Res Team, Ribeirao Preto - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Inflammat & Pain, Ribeirao Preto - Brazil
[4] Univ Estadual Londrina, Ctr Hlth Sci, Dept Pharmaceut Sci, Londrina - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Citações Web of Science: 1

Background: Gout is the most common inflammatory arthritis worldwide. It is a painful inflammatory disease induced by the deposition of monosodium urate (MSU) crystals in the joints and peri-articular tissues. Sesquiterpene lactones (SLs) are secondary metabolite biosynthesized mainly by species from the family Asteraceae. It has been demonstrated that SLs present anti-inflammatory, analgesic, antitumoral, antiparasitic, and antimicrobial activities. In this study, we aimed at evaluating the efficacy of the SL budlein A in a model of acute gout arthritis in mice. Methods: Experiments were conducted in male Swiss or male LysM-eGFP mice. Animals were treated with budlein A (1 or 10 mg/kg) or vehicle 30 min before stimulus with MSU (100 mu g/10 mu L, intra-articular). Knee joint withdrawal threshold and edema were evaluated using electronic von Frey and caliper, respectively, 1-15 h after MSU injection. Leukocyte recruitment was determined by counting cells (Neubauer chamber), H\&E staining, and using LysM-eGFP mice by confocal microscopy. Inflammasome components, Il-1 beta and Tnf-alpha mRNA expression were determined by RT-qPCR. IL-1 beta and TNF-alpha production (in vitro) and NF-kappa B activation (in vitro and in vivo) were evaluated by ELISA. In vitro analysis using LPS-primed bone marrow-derived macrophages (BMDMs) was performed 5 h after stimulation with MSU crystals. For these experiments, BMDMs were either treated or pre-treated with budlein A at concentrations of 1, 3, or 10 mu g/mL. Results: We demonstrated that budlein A reduced mechanical hypersensitivity and knee joint edema. Moreover, it reduced neutrophil recruitment, phagocytosis of MSU crystals by neutrophils, and Il-1 beta and Tnf-alpha mRNA expression in the knee joint. In vitro, budlein A decreased TNF-alpha production, which might be related to the inhibition of NF-kappa B activation. Furthermore, budlein A also reduced the IL-1 beta maturation, possibly by targeting inflammasome assembly in macrophages. Conclusion: Budlein A reduced pain and inflammation in a model of acute gout arthritis in mice. Therefore, it is likely that molecules with the ability of targeting NF-kappa B activation and inflammasome assembly, such as budlein A, are interesting approaches to treat gout flares. (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