Effects of budlein A on human neutrophils and lymphocytes

Knob, Carollinie Dias; Silva, Milena da; Gasparoto, Thaís Helena; Oliveira, Carine Ervolino de; Amôr, Nádia Ghinelli; Arakawa, Nilton Syogo; Costa, Fernando B. Da; Campanelli, Ana Paula

doi:10.1590/1678-775720150540

Cited by 3 publications

(3 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These inflammatory mediators are detected by vagus nerve and inform the brain about peripheral inflammation (Tracey, 2002; Watkins et al, 1995). IL-6, TNF-α, IL-12, IL-1 alpha and CXCl1 have all previously been shown to play a detrimental role in stroke (Boutin et al, 2001; Losy et al, 2005; Whiteley et al, 2009) and are secreted by monocytes, macrophages and neutrophils (Cai et al, 2016; Chimen et al, 2017; Farahi et al, 2017; Knob et al, 2016; Nowicki et al, 2017; Sica et al, 2012). Interestingly, splenectomy in both sham and stroke animals resulted in a decline in pro-inflammatory cytokines, suggesting a role of spleen in cytokine modulation.…”

Section: Discussionmentioning

confidence: 99%

Splenectomy protects aged mice from injury after experimental stroke

Chauhan

Mamun

Spiegel

et al. 2018

Neurobiology of Aging

View full text Add to dashboard Cite

Elderly stroke patients and aged animals subjected to experimental stroke have significantly worse functional recovery and higher mortality compared to younger subjects. Activation of the peripheral immune system is known to influence stroke outcome. Prior studies have shown that splenectomy reduces ischemic brain injury in young mice. As immune function changes with aging, it is unclear whether splenectomy will confer similar benefits in aged animals. We investigated the contribution of spleen to brain injury after cerebral ischemia in aged male mice. Splenic architecture and immune cell composition were altered in aged mice. Splenectomy 2 weeks before stroke resulted in improved neurobehavioral and infarct outcomes in aged male mice. In addition, there was a reduction in peripheral immune cell infiltration into the brain and decreased levels of peripheral inflammatory cytokines after stroke in aged splenectomized mice. Splenectomy immediately after reperfusion also improved behavioral and infarct outcomes. This study suggests that inhibition of the splenic immune response is a translationally relevant target to pursue for stroke treatment in aged individuals.

show abstract

Section: Discussionmentioning

confidence: 99%

Splenectomy protects aged mice from injury after experimental stroke

Chauhan

Mamun

Spiegel

et al. 2018

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…Moreover, strategies aiming at controlling the initial recruitment of neutrophils are interesting approaches for pain relief in gout arthritis. Previous evidence shows that budlein A inhibits neutrophil recruitment ( Valerio et al, 2007 ; Arakawa et al, 2008 ; Nicolete et al, 2009 ; Knob et al, 2016 ; Zarpelon et al, 2017 ) and activation as observed by a reduction in neutrophil elastase release ( Arakawa et al, 2008 ), an enzyme released in the neutrophil extracellular traps (NETs) ( Fattori et al, 2016 ). In the present work, we demonstrate that budlein A reduced MSU-induced neutrophil recruitment, as observed in the reduced number of LysM-eGFP positive cells in the knee joint, decreased levels of MPO activity, and reduced number neutrophils in the Neubauer chamber.…”

Section: Discussionmentioning

confidence: 99%

“…Gardner (Brazilian Arnica , Asteraceae) containing the SL goyazensolide (the major metabolite) ameliorated oxonate-induced hyperuricemia in mice, indicating that they could be also used as urate-lowering therapies ( de Albuquerque Ugoline et al, 2017 ). Budlein A is an SL with analgesic ( Valerio et al, 2007 ; Zarpelon et al, 2017 ) and anti-inflammatory properties ( Valerio et al, 2007 ; Arakawa et al, 2008 ; Nicolete et al, 2009 ; Knob et al, 2016 ; Zarpelon et al, 2017 ) related to the inhibition of pro-inflammatory cytokines and neutrophil recruitment. Mechanistically, SLs can inhibit NF-κB activation ( Lyss et al, 1998 ; Siedle et al, 2004 ; Zhao et al, 2015 ; Widen et al, 2017 ; Zarpelon et al, 2017 ) or even direct target inflammasome assembly ( Juliana et al, 2010 ; Mathema et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

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 μg/10 μL, 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-1β, and Tnf-α mRNA expression were determined by RT-qPCR. IL-1β and TNF-α production (in vitro) and NF-κB 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 μg/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-1β and Tnf-α mRNA expression in the knee joint. In vitro, budlein A decreased TNF-α production, which might be related to the inhibition of NF-κB activation. Furthermore, budlein A also reduced the IL-1β 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-κB activation and inflammasome assembly, such as budlein A, are interesting approaches to treat gout flares.

show abstract

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

et al. 2017

View full text Add to dashboard Cite

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

show abstract

Effects of budlein A on human neutrophils and lymphocytes

Cited by 3 publications

References 29 publications

Splenectomy protects aged mice from injury after experimental stroke

Splenectomy protects aged mice from injury after experimental stroke

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

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

Contact Info

Product

Resources

About