High cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) contents in mouse lung tumors

Indomethacin and related nonsteroidal anti-inflammatory drugs relax prostanoid-dependent intrinsic tone of isolated guinea pig trachea by inhibiting cyclooxygenase (COX). Recently, a second isoform of COX (COX-2) was discovered, which differed from COX-1 with respect to protein structure, transcriptional regulation, and susceptibility to inhibition by pharmacological agents. It is now known that indomethacin nonselectively inhibits COX-1 and COX-2, whereas NS-398 is a selective inhibitor of COX-2. In the present study we compared the activity of a selective (NS-398) and nonselective (indomethacin) COX-2 inhibitor on intrinsic tone of isolated guinea pig trachea. NS-398 ≥ indomethacin produced a reversal of intrinsic tone with a similar concentration-dependent (10 nM to 1 μM) time course (Tmax approximately 20–45 min), potency (EC50 1.7 and 5.6 nM, respectively), and maximal response. Contractions to cholinergic nerve stimulation (45 V, 0.5 ms, 0.1–32 Hz) and histamine were similarly modulated in tissues relaxed with the selective or nonselective COX-2 inhibitors. Immunoblot analyses showed that COX-2 protein synthesis was induced in both the cartilage and smooth muscle portions of the trachea during changes in intrinsic tone. These findings are consistent with pharmacological results and provide the first demonstration that prostanoid tone in isolated guinea pig trachea is dependent on COX-2 activity. The results also suggest that the activity of indomethacin in this preparation is likely related to COX-2 inhibition.Key words: cyclooxygenase 2, relaxation, guinea pig trachea, cyclooxygenase 1.

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Role of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) derived prostaglandins (PG) in adaptive cytoprotection induced by mild stress

Gastroenterology ◽

10.1016/s0016-5085(98)80332-6 ◽

1998 ◽

Vol 114 ◽

pp. A82

Author(s):

T. Brzozowski ◽

P.C. Konturek ◽

R. Pajdo ◽

N. Nagraba ◽

A. Szczeklik ◽

...

Keyword(s):

Cyclooxygenase 2 ◽

Mild Stress ◽

Adaptive Cytoprotection ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Cox 1

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The Biological Function Prediction of The 10-gingerol Compound of Ginger in Inhibiting Cyclooxygenase-2 Activity

The Journal of Pure and Applied Chemistry Research ◽

10.21776/ub.jpacr.2020.009.03.547 ◽

2020 ◽

Vol 9 (3) ◽

pp. 222-232

Author(s):

Gabriella Chandrakirana Krisnamurti ◽

◽

Fatchiyah Fatchiyah ◽

◽

...

Keyword(s):

Catalytic Domain ◽

Specific Binding ◽

Membrane Binding ◽

Binding Domain ◽

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

Mechanism Of Inhibition ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Anti-inflammatory agents inhibit prostaglandin synthesis by blocking cyclooxygenases (COXs). The compounds extracted from ginger, 10-gingerol and 10-shogaol can inhibit inflammation but the mechanism of inhibition remains unclear. Here we used molecular docking to predict the molecular interactions between COXs and the three inhibitors, acetaminophen (CID1983), 10-gingerol (CID168115) and 10-shogaol (CID6442612). By using that acetaminophen as a gold standard, the results demonstrated that acetaminophen, 10-gingerol, and 10-shogaol could bind catalytic domain and membrane binding domain of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). The 10-shogaol did not show significantly different binding energy to bind to COX-1 and COX-2. The 10-gingerol posed a stronger and more specific binding to the membrane-binding domain of COX-2 than acetaminophen and 10-shogaol. The specific binding of the 10-gingerol to COX-2 could prevent the binding of the natural substrate, arachidonic acid. The results provide useful information to improving activities of anti-inflammatory.

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Cyclooxygenase-1 (COX-1); cyclooxygenase-2 (COX-2)

Science-Business eXchange ◽

10.1038/scibx.2008.290 ◽

2008 ◽

Vol 1 (12) ◽

pp. 290-290

Keyword(s):

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Cox 1

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Studi In Silico Senyawa Alkaloid Herba Bakung Putih (Crinum Asiaticum L.) pada Penghambatan Enzim Siklooksigenase (COX)

Jurnal Kimia VALENSI ◽

10.15408/jkv.v4i2.7686 ◽

2018 ◽

Vol 4 (2) ◽

pp. 124-136

Author(s):

Rizky Arcinthya Rachmania ◽

Hariyanti Hariyanti ◽

Ririh Zikriah ◽

Aditya Sultan

Keyword(s):

Molecular Docking ◽

Tissue Injury ◽

Protein Docking ◽

Enzyme Activation ◽

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Anti Inflammatory ◽

Crinum Asiaticum ◽

Cox 1

Inflammation is a response to tissue injury involving the physiological process of cyclooxygenase enzyme activation which has two isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. The use of anti-inflammatory drugs of Non Steroidal Anti Inflammatory (AINS) and steroid groups has side effects in long-term use. The objective of this study was to find out eight active white herbic alkaloid compounds (Crinum asiaticum L.) to be used as anti-inflammatory by inhibiting COX-1 and COX-2 enzymes. Molecular docking method for the prediction of complex structures of proteins called ligand-protein docking using the PLANTS 1.2 software. where the lowest ChemPLP score which is free energy is the molecular tethering parameter. The herbaceous white herbaceae compound obtained the lowest CHEMPLP score of hippadine -83.3684 Kcal / mol and pratorimin -83.2661 Kcal / mol and aspirin comparator -67.3292 Kcal / mol and paracetamol -66.3535 Kcal / mol. Molecular docking in COX-2 shows lycobetaine -87.3991 Kcal / mol is lower than that of the celecoxib -85.3729 Kcal / mol comparator against the cyclooxygenase-2 receptor (COX-2). These results show that the white lycopene alkaloid compounds hyppadine, pratorimin and lycobetaine have better affinity and stability than the comparative compounds. The results of drug scans, hippadin, pratorimin and lycobetaine have the criteria for oral preparations. It can be concluded that herbaceous white herbaceae are predicted to have potential as anti-inflammatory compounds.

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In vitro and In Silico Studies on Curcumin and Its Analogues as Dual Inhibitors for cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2)

ITB journal of Sciences ◽

10.5614/itbj.sci.2012.44.1.5 ◽

2012 ◽

Vol 44 (1) ◽

pp. 51-66 ◽

Cited By ~ 2

Author(s):

Nunung Yuniarti ◽

Perdana Adhi Nugroho ◽

Aditya Asyhar ◽

Sardjiman Sardjiman ◽

Zullies Ikawati ◽

...

Keyword(s):

In Silico ◽

Cyclooxygenase 2 ◽

Cyclooxygenase 1 ◽

In Silico Studies ◽

Dual Inhibitors ◽

Cox 2 ◽

Cox 1

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Impact of Wines and Wine Constituents on Cyclooxygenase-1, Cyclooxygenase-2, and 5-Lipoxygenase Catalytic Activity

Mediators of Inflammation ◽

10.1155/2014/178931 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 29

Author(s):

Zsofia Kutil ◽

Veronika Temml ◽

David Maghradze ◽

Marie Pribylova ◽

Marcela Dvorakova ◽

...

Keyword(s):

Western Europe ◽

Biosynthetic Pathway ◽

Red Wine ◽

Complex Mixture ◽

Cyclooxygenase 2 ◽

Red Wines ◽

Strong Inhibitor ◽

Cyclooxygenase 1 ◽

Cox 2 ◽

Cox 1

Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation and later the development of atherosclerosis. Red wines from Georgia and central and western Europe inhibited cyclooxygenase-1 (COX-1) activity in the range of 63–94%, cyclooxygenase-2 (COX-2) activity in the range of 20–44% (tested at a concentration of 5 mL/L), and 5-lipoxygenase (5-LOX) activity in the range of 72–84% (at a concentration of 18.87 mL/L). White wines inhibited 5-LOX in the range of 41–68% at a concentration of 18.87 mL/L and did not inhibit COX-1 and COX-2. Piceatannol (IC50= 0.76 μM) was identified as a strong inhibitor of 5-LOX followed by luteolin (IC50= 2.25 μM), quercetin (IC50= 3.29 μM), and myricetin (IC50= 4.02 μM).trans-Resveratrol was identified as an inhibitor of COX-1 (IC50= 2.27 μM) and COX-2 (IC50= 3.40 μM). Red wine as a complex mixture is a powerful inhibitor of COX-1, COX-2, and 5-LOX, the enzymes involved in eicosanoid biosynthetic pathway.

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Non-steroidal anti-inflammatory drugs dampen the cytokine and antibody response to SARS-CoV-2 infection

Journal of Virology ◽

10.1128/jvi.00014-21 ◽

2021 ◽

Cited By ~ 1

Author(s):

Jennifer S. Chen ◽

Mia Madel Alfajaro ◽

Ryan D. Chow ◽

Jin Wei ◽

Renata B. Filler ◽

...

Keyword(s):

Immune Response ◽

Viral Replication ◽

Cyclooxygenase 2 ◽

Nsaid Treatment ◽

Susceptibility To Infection ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Abstract Identifying drugs that regulate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its symptoms has been a pressing area of investigation during the coronavirus disease 2019 (COVID-19) pandemic. Nonsteroidal anti-inflammatory drugs (NSAIDs), which are frequently used for the relief of pain and inflammation, could modulate both SARS-CoV-2 infection and the host response to the virus. NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which mediate the production of prostaglandins (PGs). As PGs play diverse biological roles in homeostasis and inflammatory responses, inhibiting PG production with NSAIDs could affect COVID-19 pathogenesis in multiple ways, including: (1) altering susceptibility to infection by modifying expression of angiotensin-converting enzyme 2 (ACE2), the cell entry receptor for SARS-CoV-2; (2) regulating replication of SARS-CoV-2 in host cells; and (3) modulating the immune response to SARS-CoV-2. Here, we investigate these potential roles. We demonstrate that SARS-CoV-2 infection upregulates COX-2 in diverse human cell culture and mouse systems. However, suppression of COX-2 by two commonly used NSAIDs, ibuprofen and meloxicam, had no effect on ACE2 expression, viral entry, or viral replication. In contrast, in a mouse model of SARS-CoV-2 infection, NSAID treatment reduced production of pro-inflammatory cytokines and impaired the humoral immune response to SARS-CoV-2 as demonstrated by reduced neutralizing antibody titers. Our findings indicate that NSAID treatment may influence COVID-19 outcomes by dampening the inflammatory response and production of protective antibodies rather than modifying susceptibility to infection or viral replication. Importance Public health officials have raised concerns about the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating symptoms of coronavirus disease 2019 (COVID-19). NSAIDs inhibit the enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), which are critical for the generation of prostaglandins – lipid molecules with diverse roles in homeostasis and inflammation. Inhibition of prostaglandin production by NSAIDs could therefore have multiple effects on COVID-19 pathogenesis. Here, we demonstrate that NSAID treatment reduced both the antibody and pro-inflammatory cytokine response to SARS-CoV-2 infection. The ability of NSAIDs to modulate the immune response to SARS-CoV-2 infection has important implications for COVID-19 pathogenesis in patients. Whether this occurs in humans and whether it is beneficial or detrimental to the host remains an important area of future investigation. This also raises the possibility that NSAIDs may alter the immune response to SARS-CoV-2 vaccination.

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Differential expression of cyclooxygenase 1 and cyclooxygenase 2 in the bovine oviduct

Journal of Endocrinology ◽

10.1677/joe.1.06761 ◽

2006 ◽

Vol 191 (1) ◽

pp. 263-274 ◽

Cited By ~ 29

Author(s):

Simone Odau ◽

Christoph Gabler ◽

Christoph Holder ◽

Ralf Einspanier

Keyword(s):

Mrna Expression ◽

Estrous Cycle ◽

Luteal Phase ◽

Cellular Level ◽

Differential Distribution ◽

Cyclooxygenase 1 ◽

Epithelial Cell Layer ◽

Cox 2 ◽

Cycle Dependent ◽

Cox 1

The aim of the present study was to investigate the enzymes for the local prostaglandin (PG) biosynthesis present in the bovine oviduct during the estrous cycle to influence early reproductive events. Bovine oviducts were classified into four phases: pre-ovulatory, post-ovulatory, early-to-mid luteal, and late luteal phase, subdivided further into ipsi- or contralateral site and separated into ampulla or isthmus. Oviductal cells were gained by flushing the oviductal regions. Quantitative real-time reverse transcriptase-PCR was performed for the secretory and cytosolic phospholipases A2 (sPLA2IB, cPLA2α, and cPLA2β) and cyclooxygenases (COX-1 and COX-2) as the first step enzymes of PG synthesis. COX-1 and cPLA2β showed significant highest mRNA expression around and before ovulation compared with the luteal phase respectively. sPLA2IB and cPLA2α mRNA expression was unregulated during the estrous cycle. Regional differences in mRNA content were found for sPLA2IB with higher mRNA expression in the ampulla than in the isthmus. Western blot analysis revealed the highest COX-1 protein content in the early-to-mid luteal phase. Immunohistochemistry demonstrated that COX-1 was localized in epithelial and smooth muscle cells, whereas COX-2 was only localized in epithelial cells. COX-2 showed a differential distribution within the epithelial cell layer suggesting a regulation on a cellular level, although the COX-2 mRNA and protein amounts did not vary throughout the estrous cycle. A COX activity assay of oviductal cells revealed that COX activity originated predominantly from COX-1 than from COX-2. Treatment of primary oviductal cells with 10 pg/ml 17β-estradiol or 10 ng/ml progesterone resulted in a higher expression of COX-2 and cPLA2α, but not of the other enzymes. The expression pattern of these enzymes suggests that an estrous-cycle dependent and region-specific PG synthesis in the bovine oviduct may be required for a successful reproduction.

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Meloxicam in pain syndrome treatment of comorbid diseases patients

Medical Council ◽

10.21518/2079-701x-2021-19-209-215 ◽

2021 ◽

pp. 209-215

Author(s):

O. A. Shavlovskaya ◽

I. A. Bokova ◽

N. I. Shavlovskiy

Keyword(s):

Gastrointestinal Tract ◽

Pain Syndrome ◽

Cardiovascular Risks ◽

Lower Back ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Comorbid Diseases ◽

Per Oral ◽

Cox 1

The issue nonsteroidal anti-inflammatory drugs (NSAIDs) use safety is associated with a high frequency of adverse events (AEs) from the gastrointestinal tract and cardiovascular risks. Patients with lower back pain (LBP) and osteoarthritis (OA), as a rule, have comorbid diseases, such as arterial hypertension (AH), coronary heart disease (CHD), gastrointestinal tract (GIT) diseases, which significantly complicates the appointment of NSAIDs. The main guideline in NSAIDs appointment is the selective ability to inhibit cyclooxygenase-1 and -2 (COX). The ratio of the activity of NSAIDs when blocking COX-1/COX-2 allows us to judge their potential toxicity. And, then higher the selectivity of NSAIDs, then lower its toxicity. For example, the ratio of COX-1/COX-2 in meloxicam is 0.33, diclofenac – 2.2, tenoxicam – 15, piroxicam – 33, indomethacin – 107. To the predominantly selective COX-2 NSAIDs include meloxicam, which has little effect on the GIT, the lowest relative risk (RR) of complications from the cardiovascular system (CVS). The therapeutic efficacy of meloxicam is comparable to piroxicam and diclofenac. A number of studies have shown the high efficacy of meloxicam, both with per oral (p/o) administration (7.5–15 mg/d), and with intramuscular (i/m) administration (1.5 ml), and when injected into trigger zones. Both with p/o and the injectable form of meloxicam has minimal GIT AEs and absence local reaction in the injection area. The drug can be recommended both as a combination therapy and prescribed in monotherapy.

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