Effects of valeryl salicylate, a COX-1 inhibitor, on models of acute inflammation in mice

Siqueira-Junior, J.M.; Peters, Rodrigo Rebelo; Brum‐Fernandes, Artur J. de; Ribeiro‐do‐Valle, Rosa Maria

doi:10.1016/s1043-6618(03)00188-9

Cited by 23 publications

(17 citation statements)

References 26 publications

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“…To assess the in vivo efficacy of G␤␥-binding small molecules in blocking neutrophil chemotaxis we tested gallein in the carrageenan paw edema model. Carrageenan, when injected into the glabrous tissue of the hind paw, leads to rapid acute inflammation characterized by infiltration of neutrophils (Siqueira-Junior et al, 2003). Gallein or vehicle control was delivered by intraperitoneal injection 1 h before injection of carrageenan into the paw.…”

Section: Inhibition Of G Protein-dependent Chemotactic Peptide Signalmentioning

confidence: 99%

“…4A). Indomethacin, a nonselective nonsteroidal antiinflammatory drug that inhibits cyclooxygenases 1 and 2 (Siqueira-Junior et al, 2003), is the drug of choice for comparative in vivo efficacy studies. Pretreatment with indomethacin sharply reduced paw edema.…”

Section: Inhibition Of G Protein-dependent Chemotactic Peptide Signalmentioning

confidence: 99%

“…4B). Acute phase inflammation, as seen in the carrageenan-induced paw edema model, is characterized by neutrophil infiltration (Siqueira-Junior et al, 2003;Posadas et al, 2004). To confirm that neutrophil infiltration was inhibited, the number of neutrophils in paw exudates was quantified.…”

Section: Inhibition Of G Protein-dependent Chemotactic Peptide Signalmentioning

confidence: 99%

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Small Molecule Disruption of G Protein βγ Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation

Lehmann¹,

Seneviratne²,

Smrcka³

2007

Mol Pharmacol

209

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G protein ␤␥ subunit-dependent signaling is important for chemoattractant-dependent leukocyte chemotaxis. Selective small molecule targeting of phosphoinositide 3-kinase (PI3-kinase) ␥ catalytic activity is a target of interest for anti-inflammatory pharmaceutical development. In this study, we examined whether small-molecule inhibition of G␤␥-dependent signaling, including G␤␥-dependent activation of PI3-kinase ␥ and Rac1, could inhibit chemoattractant-dependent neutrophil migration in vitro and inflammation in vivo. Small-molecule G␤␥ inhibitors suppressed fMLP-stimulated Rac activation, superoxide production, and PI3-kinase activation in differentiated HL60 cells. These compounds also blocked fMLP-dependent chemotaxis in HL60 cells and primary human neutrophils. Systemic administration inhibited paw edema and neutrophil infiltration in a mouse carrageenan-induced paw edema model. Overall, the data demonstrate that targeting G␤␥-regulation may be an effective anti-inflammation strategy.Chemoattractant-mediated recruitment of leukocytes is responsible for many of the deleterious effects of chronic inflammatory diseases. Many chemoattractants activate G protein-coupled receptors (GPCRs) coupled to the G i family of heterotrimeric G proteins in leukocytes. Heterotrimeric G proteins are composed of G␣, G␤, and G␥ subunits. Ligand binding to receptors catalyzes the exchange of tightly bound GDP for GTP on the G␣ subunit, liberating it from the G␤␥ subunits. Dissociation of the G␣ and G␤␥ subunits can allow each to directly bind to downstream effector proteins (Gilman, 1987;Oldham and Hamm, 2006). The free G␤␥ subunits released from G i heterotrimers upon chemoattractant receptor activation initiate critical signaling pathways to direct chemoattractant-dependent neutrophil functions including chemotaxis and superoxide production (Neptune and Bourne, 1997).Key direct targets of G␤␥ subunit binding and activation in neutrophils are phosphoinositide 3-kinase ␥ (PI3-kinase ␥) (Stephens et al., 1994(Stephens et al., , 1997Stoyanov et al., 1995), Phospholipase C ␤ (PLC␤) , and P-Rex (Welch et al., 2002). PI3-kinase ␥ has been noted to be a central mediator of chemotaxis and plays a pivotal role in leukocyte recruitment to inflamed tissues (Hirsch et al., 2000;Li et al., 2000;Camps et al., 2005). PIP 3 , produced by PI3-kinase ␥ catalytic activity, is critical to the development of cell polarity, which is necessary for chemokine-mediated cell motility and directional sensing . PI3-kinase ␥-deficient neutrophils have impaired responses to various chemoattractants, including diminished chemotaxis (Hirsch et al., 2000;Li et al., 2000) and respiratory burst (Li et al., 2000;Sasaki et al., 2000), in response to GPCR activation. Small-molecule inhibitors of PI3-kinase ␥ catalytic activity have been demonstrated to suppress joint inflammation in mouse models of inflammation (Barber et al., 2005;Camps et al., 2005). Critical to the success of a method that targets PI3-kinase ␥ activity as a therapeutic anti-inflammatory a...

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Section: Inhibition Of G Protein-dependent Chemotactic Peptide Signalmentioning

confidence: 99%

Section: Inhibition Of G Protein-dependent Chemotactic Peptide Signalmentioning

confidence: 99%

See 1 more Smart Citation

Small Molecule Disruption of G Protein βγ Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation

Lehmann¹,

Seneviratne²,

Smrcka³

2007

Mol Pharmacol

209

View full text Add to dashboard Cite

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“…This effect is within the range of drugs such as salicylates injected i.p. (Siqueira-Junior et al, 2003). However, IA and IN are practically insoluble in water and poorly soluble in other solvents used for injection to animals or in cell systems.…”

mentioning

confidence: 99%

Incensole Acetate, a Novel Anti-Inflammatory Compound Isolated fromBoswelliaResin, Inhibits Nuclear Factor-κB Activation

Moussaieff

Shohami²,

Kashman³

et al. 2007

Mol Pharmacol

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Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the antiinflammatory effect of the resin, using inhibitor of nuclear factor-B␣ (IB␣) degradation in tumor necrosis factor (TNF) ␣-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-B (NF-B) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-B activation. It had no effect on IKK activity in vitro, and it did not suppress IB␣ phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-B activation pathways. The inhibitory effect seems specific; IA did not interfere with TNF␣-induced activation of c-Jun Nterminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-B inhibitors, originating from an ancient anti-inflammatory herbal remedy.

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“…Development of edema in the paw of the rat after the injection of carrageenan involves three phases by several inflammatory mediators released in an ordinary sequence. An initial phase during the first 1.5 h is caused by the release of histamine and serotonin, the second phase is mediated by bradykinin-like substances from 1.5 to 2.5 h. The treatment with the COX-1 inhibitor could reduce the first and second phases of paw edema 35 .…”

Section: Resultsmentioning

confidence: 99%

Untitled

2013

IJPSR

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ABSTRACT:In the present study, novel derivatives of substituted cisstilbene were prepared from benzyl (chloro) triphenyl phosphorane, substituted phenyl acetic acid and In vivo anti-inflammatory activity was evaluated by carrageenan-induced rat paw edema assay model. The newly synthesized compounds were characterized by IR, 1 H NMR and Mass analyses. The results revealed that all the test compounds protected the rats from carrageenan induced inflammation and the test compounds showed a significant anti-inflammatory activity against the control group. Among the compounds tested 1i, 1l, 1o, 2c, 2d, 2h, 3b and 3d showed better anti-inflammatory activity and 2f, 3c showed moderate activity.

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Effects of valeryl salicylate, a COX-1 inhibitor, on models of acute inflammation in mice

Cited by 23 publications

References 26 publications

Small Molecule Disruption of G Protein βγ Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation

Small Molecule Disruption of G Protein βγ Subunit Signaling Inhibits Neutrophil Chemotaxis and Inflammation

Incensole Acetate, a Novel Anti-Inflammatory Compound Isolated fromBoswelliaResin, Inhibits Nuclear Factor-κB Activation

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