scholarly journals Ellagic acid inhibits lipopolysaccharide-induced expression of enzymes involved in the synthesis of prostaglandin E2 in human monocytes

2009 ◽  
Vol 103 (8) ◽  
pp. 1102-1109 ◽  
Author(s):  
Sofia Karlsson ◽  
Eewa Nånberg ◽  
Christina Fjaeraa ◽  
Jonny Wijkander
Keyword(s):  
Ellagic Acid ◽  
Inhibitory Effect ◽  
Ionophore A23187 ◽  
Human Monocytes ◽  
Cytosolic Phospholipase ◽  
Natural Polyphenol ◽  
The Subject ◽  
Cox 2 ◽  
Cancer And Inflammation ◽  
Cox 1

Ellagic acid, a natural polyphenol found in certain fruits, nuts and vegetables, has in recent years been the subject of intense research within the fields of cancer and inflammation. Pain, fever and swelling, all typical symptoms of inflammation, are ascribed to elevated levels of PGE2. In the present study, we have investigated the effects of ellagic acid on PGE2 release and on prostaglandin-synthesising enzymes in human monocytes. Ellagic acid was found to inhibit Ca ionophore A23187-, phorbol myristate acetate- and opsonised zymosan-induced release of PGE2 from monocytes pre-treated with the inflammatory agent lipopolysaccharide. Ellagic acid suppressed the lipopolysaccharide-induced increase in protein expression of cyclo-oxygenase-2 (COX-2), microsomal PGE synthase-1 (mPGEs-1) and cytosolic phospholipase A2α (cPLA2α), while it had no effect on the constitutively expressed COX-1 protein. Ellagic acid had no apparent inhibitory effect on these enzymes when the activities were determined in cell-free assays. We conclude that the inhibitory effect of ellagic acid on PGE2 release from monocytes is due to a suppressed expression of COX-2, mPGEs-1 and cPLA2α, rather than a direct effect on the activities of these enzymes.

scholarly journals Inhibitory Effect of Methyleugenol on IgE-Mediated Allergic Inflammation in RBL-2H3 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Tang ◽  
Feilong Chen ◽  
Xiao Ling ◽  
Yao Huang ◽  
Xiaomei Zheng ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Therapeutic Drugs ◽  
Cytosolic Phospholipase ◽  
Ige Mediated ◽  
Cox 2 ◽  
Mast Cell Line

Allergic diseases, such as asthma and allergic rhinitis, are common. Therefore, the discovery of therapeutic drugs for these conditions is essential. Methyleugenol (ME) is a natural compound with antiallergic, antianaphylactic, antinociceptive, and anti-inflammatory effects. This study examined the antiallergic effect of ME on IgE-mediated inflammatory responses and its antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME significantly inhibited the release ofβ-hexosaminidase, tumor necrosis factor- (TNF-)α, and interleukin- (IL-) 4, and was not cytotoxic at the tested concentrations (0–100 μM). Additionally, ME markedly reduced the production of the proinflammatory lipid mediators prostaglandin E2(PGE2), prostaglandin D2(PGD2), leukotriene B4(LTB4), and leukotriene C4(LTC4). We further evaluated the effect of ME on the early stages of the FcεRI cascade. ME significantly inhibited Syk phosphorylation and expression but had no effect on Lyn. Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is implicated in proinflammatory cytokine expression. ME also decreased cytosolic phospholipase A2(cPLA2) and 5-lipoxygenase (5-LO) phosphorylation and cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2, and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also contribute to the antiallergic action of ME. Our study provides further information about the biological functions of ME.

scholarly journals Inhibitory effect of LY 255283 on the synthesis of leukotriene B4and thromboxane A2in human peripheral blood polymorphonuclear leukocytes and monocytes

1993 ◽  
Vol 2 (6) ◽  
pp. 407-409 ◽  
Author(s):  
M. Ugur ◽  
M. Melli
Keyword(s):  
Receptor Antagonist ◽  
Peripheral Blood ◽  
Polymorphonuclear Leukocytes ◽  
Human Peripheral Blood ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Human Monocytes

LY 255283 [(1-(5-ethyl-2-hydroxy-4-(6-methyl-6-)1H-tetrazol-5-yl)-heptyloxy) phenyl)ethanone], a specific leukotriene B4(LTB4) receptor antagonist, inhibited the production of LTB4in human peripheral blood polymorphonuclear leukocytes (PMNL) and in monocytes activated by calcium ionophore A23187. In human monocytes activated by ionophore it inhibited also the production of thromboxane B2(TXB2). The effect of LY 255283 on 5-lipoxygenase (5-LO) and LTA4hydrolase activities which catalyse the production of LTB4and LTA4has not been studied yet. It is thought that LY 255283 may inhibit the production of LTB4and TXA2by antagonising the effect of ionophore-induced LTB4on 5-lipoxygenase and cyclooxygenase in human peripheral blood PMNL and monocytes.

scholarly journals New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 659
Author(s):  
Christophe Tratrat ◽  
Michelyne Haroun ◽  
Aliki Paparisva ◽  
Charalmpos Kamoutsis ◽  
Anthi Petrou ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Cyclooxygenase Inhibitors ◽  
Good Prediction ◽  
Docking Analysis ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Almost All ◽  
Inflammatory Action ◽  
Cox 1

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

scholarly journals Different Chemical Structures and Physiological/Pathological Roles of Cyclooxygenases

2020 ◽  
Author(s):  
Yalcin Faki ◽  
◽  
Ayse Er
Keyword(s):  
Chemical Structures ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Living Things ◽  
The Subject ◽  
Cox 2 ◽  
The Brain ◽  
Different Levels ◽  
Cox 1 ◽  
Different Tissues

This review describes cyclooxygenase (COX), which synthesizes prostanoids that play an important role in living things. The authors conducted a national and international literature review on the subject. The COX enzyme uses arachidonic acid to form prostanoids, which play a role in several physiological and pathological conditions. This enzyme has different isoforms, mainly COX-1 and COX-2. The constitutive isoform is COX-1, while COX-2 is the inducible isoform. Both are expressed in different tissues and at different levels, but they may also coexist within the same tissue. Both isoforms show essentially the same mode of action, but their substrates and inhibitors may differ. The COX-1 isoform, which plays a role in the continuation of physiological events, has an increased expression level in various carcinomas, and the COX-2 isoform, which is increased in inflammatory conditions, is typically expressed at low physiological levels in some tissues such as the brain, kidney, and uterus. In addition to investigating the efficacies of the COX-1 and COX-2 isoforms, the discovery of potential new COX enzymes and their effect continues. This review also looks at the roles of the COX enzyme in certain physiological and pathological conditions.

scholarly journals Characteristics of New Peptides GQLGEHGGAGMG, GEHGGAGMGGGQFQPV, EQGFLPGPEESGR, RLARAGLAQ, YGNPVGGVGH, and GNPVGGVGHGTTGT as Inhibitors of Enzymes Involved in Metabolic Syndrome and Antimicrobial Potential

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2492 ◽  
Author(s):  
Urszula Złotek ◽  
Anna Jakubczyk ◽  
Kamila Rybczyńska-Tkaczyk ◽  
Paula Ćwiek ◽  
Barbara Baraniak ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Antimicrobial Activity ◽  
Inhibitory Activity ◽  
Synthetic Peptides ◽  
Cytotoxic Effect ◽  
Inhibitory Effect ◽  
Converting Enzyme ◽  
Cox 2 ◽  
Enzyme I ◽  
Cox 1

The aim of this study was to determine the cytotoxic properties, influence on enzyme activity involved in metabolic syndrome, and antimicrobial activity of synthetic peptides with GQLGEHGGAGMG, GEHGGAGMGGGQFQPV, EQGFLPGPEESGR, RLARAGLAQ, YGNPVGGVGH, and GNPVGGVGHGTTGT sequences. Peptides have no cytotoxic effect on cells. The highest inhibitory effect on angiotensin converting enzyme I was noted for peptide GT-14 (IC50 = 525.63 µg/mL). None of the tested peptides had an influence on α-glucosidase. The highest α-amylase and lipase inhibitory activity was noted for GG-12 (IC50 = 56.72 and 60.62 µg/mL, respectively). The highest lipoxidase inhibitory activity was determined for peptide ER-13 (IC50 = 84.35 µg/mL). Peptide RQ-9 was characterized by the highest COX inhibitory activity (0.31 and 4.77 µg/mL for COX-1 and COX-2, respectively). Only peptide RQ-9 inhibited S. enteritidis ATCC 4931 growth (42–48%) in all tested concentrations (15.62–250 mg/mL).

scholarly journals In vitro Anti-inflammatory Activity of Ligustrum vulgare Extracts and Their Analytical Characterization

2013 ◽  
Vol 8 (11) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Anna Macková ◽  
Pavel Mučaji ◽  
Ute Widowitz ◽  
Rudolf Bauer
Keyword(s):  
Inhibitory Activity ◽  
Inhibitory Effect ◽  
Neutrophil Granulocytes ◽  
Cyclooxygenase 1 ◽  
Ligustrum Vulgare ◽  
China And Japan ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 1

Interest in the anti-inflammatory effects of Ligustrum vulgare L., which has been used traditionally in China and Japan prompted us to determine anti-inflammatory effects of the plant's compounds in leukocytes. The leaves of L. vulgare were used to prepare a decoction which was successively extracted with organic solvents (dichloromethane (DCM), n-butanol, ethyl acetate) using liquid-liquid partition. Extracts were tested for inhibition of LTB4, resp. PGE2 biosynthesis. Each extract was evaluated for its in vitro cyclooxygenase-1/2 (COX-1/2) inhibitory activity using assays with purified COX-1 and COX-2 enzymes, as well as for their LTB4 formation inhibitory activity using an assay with activated human neutrophil granulocytes. All extracts reported inhibitory actions against COXs in comparison with the synthetic inhibitors NS-398 (IC50 = 2.6 μM) and indomethacin (IC50 = 0.9 μM). The dichloromethane extract of privet leaves showed a considerable inhibitory effect against COX-1 and COX-2 enzyme activity. The DCM extract revealed 2.7 times higher inhibitory activity against LTB4 formation in comparison with the known specific LT inhibitor zileuton (IC50 = 5.0 μM). Additionally, oleuropein and echinacoside were detected by HPLC-DAD and LC-MS in the Ligustrum vulgare leaves. Both compounds exhibited weak inhibitory activity on cyclooxygenases and leukotriene formation.

scholarly journals Melatonin Modulation of Radiation and Chemotherapeutics-induced Changes on Differentiation of Breast Fibroblasts

2019 ◽  
Vol 20 (16) ◽  
pp. 3935 ◽  
Author(s):  
Alicia González-González ◽  
Enrique García Nieto ◽  
Alicia González ◽  
Cristina Sánchez-Fernández ◽  
Carolina Alonso-González ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Proliferation And Differentiation ◽  
Cox 2 ◽  
Regulatory Effects ◽  
Factor Α ◽  
Induced Changes ◽  
Pparγ Expression ◽  
Cox 1 ◽  
Breast Fibroblasts

Melatonin exerts oncostatic actions and sensitizes tumor cells to chemotherapeutics or radiation. In our study, we investigated the effects of docetaxel, vinorelbine, and radiation on human breast fibroblasts and its modulation by melatonin. Docetaxel or vinorelbine inhibits proliferation and stimulates the differentiation of breast preadipocytes, by increasing C/EBPα and PPARγ expression and by downregulating tumor necrosis factor α (TNFα), interleukin 6 (IL-6), and IL-11 expression. Radiation inhibits both proliferation and differentiation through the downregulation of C/EBPα and PPARγ and by stimulating TNFα expression. In addition, docetaxel and radiation decrease aromatase activity and expression by decreasing aromatase promoter II and cyclooxygenases 1 and 2 (COX-1 and COX-2) expression. Melatonin potentiates the stimulatory effect of docetaxel and vinorelbine on differentiation and their inhibitory effects on aromatase activity and expression, by increasing the stimulatory effect on C/EBPα and PPARγ expression and the downregulation of antiadipogenic cytokines and COX expression. Melatonin also counteracts the inhibitory effect of radiation on differentiation of preadipocytes, by increasing C/EBPα and PPARγ expression and by decreasing TNFα expression. Melatonin also potentiates the inhibitory effect exerted by radiation on aromatase activity and expression by increasing the downregulation of promoter II, and COX-1 and COX-2 expression. Our findings suggest that melatonin modulates regulatory effects induced by chemotherapeutic drugs or radiation on preadipocytes, which makes it a promising adjuvant for chemotherapy and radiotherapy sensibilization.

Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus

2004 ◽  
Vol 286 (5) ◽  
pp. R903-R909 ◽  
Author(s):  
Asmàa Bouayad ◽  
Jean-Claude Fouron ◽  
Xin Hou ◽  
Martin Beauchamp ◽  
Christiane Quiniou ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Developmental Regulation ◽  
Ductus Arteriosus ◽  
Platelet Activating Factor ◽  
Phospholipase A ◽  
Developmental Changes ◽  
Cytosolic Phospholipase ◽  
Paf Receptor ◽  
Cox 2 ◽  
Cox 1

The synthesis of PGE2, the major vasodilator prostanoid of the ductus arteriosus (DA), is catalyzed by PGE2 synthases (PGES). The factors implicated in increased PGE2 synthesis in the perinatal DA are not known. We studied the developmental changes of PGES along with that of cyclooxygenase (COX)-2 and cytosolic phospholipase A2 (cPLA2) in the DA of fetal (75-90% gestation) and immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2, and PGE2 in the DA of NB were ∼7-fold higher than in fetus; activities of cytosolic PGES (cPGES) and cPLA2 in DA of the fetus and NB did not differ. Because platelet-activating factor (PAF) could regulate COX-2 expression, the former was measured and found to be more abundant in the DA of the NB than of fetus. PAF elicited an increase in mPGES, COX-2, and PGE2 in fetal DA to levels approaching those of the NB; cPGES, cPLA2, and COX-1 were unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315 reduced mPGES, COX-2, and PGE2 levels and were associated with increased DA tone. It is concluded that PAF contributes in regulating DA tone by governing mPGES, COX-2, and ensuing PGE2 levels in the perinate.

Isolation of (S)-(+)-Naproxene from Musa acuminata. Inhibitory Effect of Naproxene and its 7-Methoxy Isomer on Constitutive COX-1 and Inducible COX-2

Planta Medica ◽  
2000 ◽  
Vol 66 (5) ◽  
pp. 471-473 ◽  
Author(s):  
T. Abad ◽  
G. McNaughton-Smith ◽  
W. Q. Fletcher ◽  
F. Echeverri ◽  
R. Diaz-Peñate ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Musa Acuminata ◽  
Cox 2 ◽  
Cox 1

scholarly journals Zymosan-induced glycerylprostaglandin and prostaglandin synthesis in resident peritoneal macrophages: roles of cyclo-oxygenase-1 and -2

2006 ◽  
Vol 399 (1) ◽  
pp. 91-99 ◽  
Author(s):  
Carol A. Rouzer ◽  
Susanne Tranguch ◽  
Haibin Wang ◽  
Hao Zhang ◽  
Sudhansu K. Dey ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peritoneal Macrophages ◽  
Prostaglandin Synthesis ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
Cytosolic Phospholipase A2α ◽  
Cox 2 ◽  
Cox 1 ◽  
Exogenous Substrates

COX [cyclo-oxygenase; PG (prostaglandin) G/H synthase] oxygenates AA (arachidonic acid) and 2-AG (2-arachidonylglycerol) to endoperoxides that are converted into PGs and PG-Gs (glycerylprostaglandins) respectively. In vitro, 2-AG is a selective substrate for COX-2, but in zymosan-stimulated peritoneal macrophages, PG-G synthesis is not sensitive to selective COX-2 inhibition. This suggests that COX-1 oxygenates 2-AG, so studies were carried out to identify enzymes involved in zymosan-dependent PG-G and PG synthesis. When macrophages from COX-1−/− or COX-2−/− mice were treated with zymosan, 20–25% and 10–15% of the PG and PG-G synthesis observed in wild-type cells respectively was COX-2 dependent. When exogenous AA and 2-AG were supplied to COX-2−/− macrophages, PG and PG-G synthesis was reduced as compared with wild-type cells. In contrast, when exogenous substrates were provided to COX-1−/− macrophages, PG-G but not PG synthesis was reduced. Product synthesis also was evaluated in macrophages from cPLA2α (cytosolic phospholipase A2α)−/− mice, in which zymosan-induced PG synthesis was markedly reduced, and PG-G synthesis was increased approx. 2-fold. These studies confirm that peritoneal macrophages synthesize PG-Gs in response to zymosan, but that this process is primarily COX-1-dependent, as is the synthesis of PGs. They also indicate that the 2-AG and AA used for PG-G and PG synthesis respectively are derived from independent pathways.

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