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

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

Full text
Author(s):
Show less -
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.
Total Authors: 12
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: FRONTIERS IN PHARMACOLOGY; v. 9, SEP 25 2018.
Web of Science Citations: 1
Abstract

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)

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