PMID- 30319413
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Budlein A, a Sesquiterpene Lactone From Viguiera robusta, Alleviates Pain and 
      Inflammation in a Model of Acute Gout Arthritis in Mice.
PG  - 1076
LID - 10.3389/fphar.2018.01076 [doi]
LID - 1076
AB  - 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 mug/10 muL, 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-1beta, and Tnf-alpha 
      mRNA expression were determined by RT-qPCR. IL-1beta and TNF-alpha production (in vitro) 
      and NF-kappaB 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 mug/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-1beta 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-kappaB activation. Furthermore, budlein A also reduced the IL-1beta 
      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-kappaB activation and inflammasome assembly, such as budlein A, are 
      interesting approaches to treat gout flares.
FAU - Fattori, Victor
AU  - Fattori V
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
FAU - Zarpelon, Ana C
AU  - Zarpelon AC
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
FAU - Staurengo-Ferrari, Larissa
AU  - Staurengo-Ferrari L
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
FAU - Borghi, Sergio M
AU  - Borghi SM
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
FAU - Zaninelli, Tiago H
AU  - Zaninelli TH
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
FAU - Da Costa, Fernando B
AU  - Da Costa FB
AD  - AsterBioChem Research Team, School of Pharmaceutical Sciences of Ribeirao Preto, 
      University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Alves-Filho, Jose C
AU  - Alves-Filho JC
AD  - Laboratory of Inflammation and Pain, Department of Pharmacology, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Cunha, Thiago M
AU  - Cunha TM
AD  - Laboratory of Inflammation and Pain, Department of Pharmacology, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Cunha, Fernando Q
AU  - Cunha FQ
AD  - Laboratory of Inflammation and Pain, Department of Pharmacology, Ribeirao Preto 
      Medical School, University of Sao Paulo, Ribeirao Preto, Brazil.
FAU - Casagrande, Rubia
AU  - Casagrande R
AD  - Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State 
      University, Londrina, Brazil.
FAU - Arakawa, Nilton S
AU  - Arakawa NS
AD  - Department of Pharmaceutical Sciences, Center of Health Sciences, Londrina State 
      University, Londrina, Brazil.
FAU - Verri, Waldiceu A Jr
AU  - Verri WA Jr
AD  - Laboratory of Pain, Inflammation, Neuropathy, and Cancer, Department of 
      Pathology, Londrina State University, Londrina, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20180925
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6167909
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - analgesia
OT  - experimental arthritis
OT  - gout treatment
OT  - joint pain
OT  - knee pain
OT  - rheumatic disease
OT  - sesquiterpene lactones
EDAT- 2018/10/16 06:00
MHDA- 2018/10/16 06:01
PMCR- 2018/09/25
CRDT- 2018/10/16 06:00
PHST- 2018/06/16 00:00 [received]
PHST- 2018/09/05 00:00 [accepted]
PHST- 2018/10/16 06:00 [entrez]
PHST- 2018/10/16 06:00 [pubmed]
PHST- 2018/10/16 06:01 [medline]
PHST- 2018/09/25 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01076 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Sep 25;9:1076. doi: 10.3389/fphar.2018.01076. eCollection 
      2018.