Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood

Ribeiro, Daniela; Freitas, Marisa; Tomé, Sara M.; Silva, Artur M. S.; Laufer, Stefan; Lima, José L.F.C.; Fernandes, Eduarda

doi:10.1007/s10753-014-9995-x

Cited by 117 publications

(95 citation statements)

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“…Indeed, xanthones 2c (not active) and 3b (holding three hydroxy groups) and xanthone 3c (with four hydroxy groups) did not reach an IC 50 at all. These data are corroborated by Ribeiro et al that previously found in structuralsimilar compounds, the less substituted flavonoids were those presenting a higher inhibitory activity [22]. This is the first paper that reports the inhibition of COX-1 activity by 2,3-diarylxanthones, but there are a few studies that explore the inhibitory capacity of other substituted xanthones using different experimental conditions.…”

Section: Discussionsupporting

confidence: 81%

“…The human whole-blood assay to assess the COX-1 inhibition was performed as previously reported [21,22]. Collected blood (500 μL) was placed in microtubes and incubated in a water bath at 37°C with TXBSI (1 μM) and the tested xanthones (0.312-100 μM) dissolved in DMSO for 15 min.…”

Section: Cox-1 Assaymentioning

confidence: 99%

“…The human whole-blood assay to assess the COX-2 inhibition was performed as previously described, with modifications [22,23]. Collected blood (800 μL) was placed in six-well plates and incubated for 15 min in a humidified incubator at 37°C with TXBSI (1 μM), acetylsalicylic acid (10 μg/mL), and the tested xanthones (1-100 μM), dissolved in a (1:10) mixture of DMSO:(chremophor/ethanol 1%).…”

Section: Cox-2 Assaymentioning

confidence: 99%

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2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

et al. 2017

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Abstract-In response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting antiinflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B 4 (LTB 4 ) formation in human neutrophils and inhibition of COX-1-and COX-2-catalyzed prostaglandin E 2 (PGE 2 ) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB 4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC 50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE 2 production presented IC 50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE 2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.

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Section: Discussionsupporting

confidence: 81%

Section: Cox-1 Assaymentioning

confidence: 99%

Section: Cox-2 Assaymentioning

confidence: 99%

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2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

et al. 2017

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“…COX-1 and COX-2 play critical roles during the transformation of arachidonic acid in prostaglandins [27, 28]. The overexpression of COX2 and prostaglandin is generated by several pro-inflammatory mediators, such as IL-1, IL-6, and TNF-α, and is related to fibrosis encapsulation, scar formation, and delayed wound healing [29, 30].…”

Section: Introductionmentioning

confidence: 99%

“…Currently, there are different non-steroidal anti-inflammatory drugs such as celecoxib and indomethacin that block COX2 and create an anti-inflammatory effect [31, 32]. In addition to this, other natural compounds, such as flavonoids, have been tested to reduce cytokine production and inhibit COX2 overproduction [28]. …”

Section: Introductionmentioning

confidence: 99%

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Yanez

Blanchette

Jabbarzadeh

2018

CPD

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Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to the identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body’s inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.

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Tissue influx of neutrophils and monocytes is delayed during development of trovafloxacin‐induced tumor necrosis factor‐dependent liver injury in mice

Giustarini

Kruijssen

Roest

et al. 2018

J of Applied Toxicology

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Idiosyncratic drug-induced liver injury (iDILI) has a poorly understood pathogenesis. However, iDILI is often associated with inflammatory stress signals in human patients as well as animal models. Tumor necrosis factor (TNF) and neutrophils play a key role in onset of trovafloxacin (TVX)-induced iDILI, but the exact role of neutrophils and other leukocytes remains to be defined. We therefore set out to study the kinetics of immunological changes during the development of TVX-induced iDILI in the established murine model of acute liver injury induced by administration of TVX and TNF. Initially, TNF stimulated the appearance of leukocytes, in particular neutrophils, into the liver of TVX-treated mice, but even more so in control mice treated with the non-DILI inducing analogue levofloxacin (LVX) or saline as vehicle (Veh). This difference was apparent at 2 hours after TNF administration, but at 4 hours, the relative neutrophil amounts were reduced again in Veh- and LVX-treated mice whereas the amounts in TVX-treated mice remained at the same increased level as at 2 hours. The influx of monocytes/macrophages, which was unaffected in Veh- and LVX-treated mice was markedly reduced or even absent in TVX-treated mice. Unlike controls, mice receiving TVX + TNF display severe hepatotoxicity with clear pathology and apoptosis, coagulated hepatic vessels and increased alanine aminotransferase levels and interleukin 6/10 ratios. Findings indicate that TVX delays the acute influx of neutrophils and monocytes/macrophages. Considering their known anti-inflammatory functions, the disruption of influx of these innate immune cells may hamper the resolution of initial cytotoxic effects of TVX and thus contribute to liver injury development.

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Flavonoids Inhibit COX-1 and COX-2 Enzymes and Cytokine/Chemokine Production in Human Whole Blood

Cited by 117 publications

References 50 publications

2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Tissue influx of neutrophils and monocytes is delayed during development of trovafloxacin‐induced tumor necrosis factor‐dependent liver injury in mice

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