Gastroprotective Effect of Myricetin on Ethanol-Induced Acute Gastric Injury in Rats

The flavonoid myricetin is abundant in vegetables and has various bioactive properties, including anti-inflammatory and antioxidative activities. In the present study, we explored the effects of myricetin on alcohol-induced gastric ulcer in a rat model. To induce gastric ulcer, absolute ethanol (5 mL/kg body weight) was orally administrated to each rat. The positive control and myricetin-treated groups were given oral doses of omeprazole (20 mg/kg) or myricetin (12 mg/kg), respectively, 1 hour prior to the administration of absolute alcohol. We found that pretreatment with myricetin significantly decreased alcohol-induced gastric ulcer, hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Myricetin pretreatment reduced the level of malondialdehyde (MDA) and increased that of total glutathione (GSSG/GSH) and superoxide dismutase (SOD) in gastric tissues. In addition, it elevated the expression levels of cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) and decreased the phosphorylation of nuclear factor kappa B (NF-κB). Together, these results indicate that myricetin effectively inhibits ethanol-induced acute gastric injury by preventing oxidative damage, stimulating PGE2 production, and inhibiting NF-κB activation. We suggest that myricetin may be an alternative treatment for gastric injury caused by alcohol intake.

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Evaluation of the antiulcerogenic activity of violacein and its modulation by the inclusion complexation with β-cyclodextrin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y03-033 ◽

2003 ◽

Vol 81 (4) ◽

pp. 387-396 ◽

Cited By ~ 28

Author(s):

Nelson Durán ◽

Giselle Z Justo ◽

Patrícia S Melo ◽

Mariângela B.M De Azevedo ◽

Alba R.M Souza Brito ◽

...

Keyword(s):

Gastric Ulcer ◽

Inclusion Complex ◽

Protective Action ◽

Inclusion Complexation ◽

Positive Control ◽

Gastric Injury ◽

Antiulcer Activity ◽

Scanning Calorimetry ◽

Molar Ratios ◽

Rat Liver Cells

The effects of β-cyclodextrin (βCD) inclusion complexation on the ability of violacein to prevent gastric ulceration in mice were studied. ViolaceinβCD inclusion complexes were prepared in 1:1 and 1:2 molar ratios and analysed by differential scanning calorimetry and powder X-ray diffractometry. Violacein previously administered orally at 10 mg/kg significantly reduced indomethacin-induced gastric lesions, as well as 100 mg/kg of cimetidine (positive control). However, βCD complexation in both molar ratios significantly potentiated the protective action of violacein. In the HClethanol-induced gastric ulcer model, violacein and the 1:2 inclusion complex (10 mg/kg, p.o.) inhibited gastric damage by almost 85%, whereas a 63% reduction was observed for the positive control, lansoprazole, at 30 mg/kg. In contrast, treatment with the 1:1 inclusion complex resulted in almost total disappearance of the antiulcer activity in this model. No significant changes in stress-induced gastric injury were found. In addition, the 1:2 inclusion complex improved the antilipoperoxidant activity of violacein in rat liver cells exposed to t-butyl hydroperoxide, whereas the 1:1 complex was less active than violacein. In summary, the 1:2 βCD inclusion complex has gastroprotective properties similar to or higher than that of violacein. An increase in mucosal defensive mechanisms and protection against peroxidative damage might be involved.Key words: violacein, β-cyclodextrin, gastric ulcer, lipid peroxidation, hepatocyte.

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Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Thrombosis and Haemostasis ◽

10.1160/th09-01-0057 ◽

2009 ◽

Vol 102 (08) ◽

pp. 336-346 ◽

Cited By ~ 35

Author(s):

Marilena Crescente ◽

Gisela Jessen ◽

Stefania Momi ◽

Hans-Dieter Höltje ◽

Paolo Gresele ◽

...

Keyword(s):

Salicylic Acid ◽

Platelet Aggregation ◽

Gallic Acid ◽

Molecular Modelling ◽

In Silico Docking ◽

Cyclooxygenase 1 ◽

Modelling Studies ◽

Cox 1

SummaryWhile resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets.We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity (arachidonic acid [AA]-induced intraplatelet ROS production); however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols. Molecular modelling studies, performed by in silico docking the polyphenols into the crystal structure of COX-1, suggested that all compounds form stable complexes into the COX-1 channel, with slightly different but functionally relevant interaction geometries. Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB2. Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex,and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of lowdose aspirin.

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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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The C50T polymorphism of the cyclooxygenase-1 gene and the risk of thrombotic events during low-dose therapy with acetyl salicylic acid

Thrombosis and Haemostasis ◽

10.1160/th08-03-0172 ◽

2008 ◽

Vol 100 (07) ◽

pp. 70-75 ◽

Cited By ~ 22

Author(s):

Martijn G. H. van Oijen ◽

Santosh Sundaresan ◽

Marc A. Brouwer ◽

Rene H. M. te Morsche ◽

Wessel Keuper ◽

...

Keyword(s):

Myocardial Infarction ◽

Platelet Aggregation ◽

Primary Endpoint ◽

Low Dose ◽

Cardiovascular Death ◽

Hazard Ratio ◽

Cyclooxygenase 1 ◽

Thromboxane Production ◽

The Common ◽

Cox 1

SummaryAspirin prevents thrombotic events by inhibiting platelet cyclooxygenase-1 (COX-1), thus reducing thromboxane A2 formation and platelet aggregation. The C50T polymorphism of COX-1 is associated with an impaired inhibition of both thromboxane production and in-vitro platelet aggregation by aspirin. We studied whether this polymorphism is also associated with the risk of clinical thrombotic events in patients using aspirin. We included 496 patients admitted to our Coronary Care Unit for various indications treated with aspirin 80 mg daily. Genotyping for the C50T polymorphism demonstrated that 86.7% of the patients had the common genotype, and 13.3% had the variant (12.5% heterozygous, 0.8% homozygous). Baseline variables were well balanced, except that patients with the common genotype more frequently used aspirin prior to admission compared to those patients with the variant genotype. The composite primary endpoint of myocardial infarction, stroke, and/or cardiovascular death occurred in 98 patients (19.8%). Myocardial infarction occurred in 9.6% of patients, stroke in 1.6%, and cardiovascular death in 12.1%.The unadjusted hazard ratio (95% CI) for the primary endpoint for patients with the variant versus the common genotype was 1.07 (0.62–1.85), p=0.8.The adjusted hazard ratio was 0.86 (0.49–1.50), p=0.6. In prior laboratory studies the COX-1 C50T polymorphism was associated with an impaired inhibitory effect of aspirin on thromboxane production and platelet function. However, in this cohort of patients using low-dose aspirin for secondary prevention the polymorphism was not associated with a higher risk of atherothrombotic events.

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Synthesis of Novel Curcumin Analogues and Their Evaluation as Selective Cyclooxygenase-1 (COX-1) Inhibitors

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.55.64 ◽

2007 ◽

Vol 55 (1) ◽

pp. 64-71 ◽

Cited By ~ 51

Author(s):

Norbert Handler ◽

Walter Jaeger ◽

Helmut Puschacher ◽

Klaus Leisser ◽

Thomas Erker

Keyword(s):

Curcumin Analogues ◽

Cyclooxygenase 1 ◽

Cox 1

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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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Involvement of cyclooxygenase 2 (COX-2) in intrinsic tone of isolated guinea pig

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y95-215 ◽

1995 ◽

Vol 73 (11) ◽

pp. 1561-1567 ◽

Cited By ~ 21

Author(s):

L. Charette ◽

C. Misquitta ◽

J. Guay ◽

D. Riendeau ◽

T. R. Jones

Keyword(s):

Guinea Pig ◽

Time Course ◽

Cyclooxygenase 2 ◽

Maximal Response ◽

Pharmacological Agents ◽

Cyclooxygenase 1 ◽

Inflammatory Drugs ◽

Cox 2 ◽

Cox 2 Inhibitors ◽

Cox 1

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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Tocotrienol Attenuates Stress-Induced Gastric Lesions via Activation of Prostaglandin and Upregulation of COX-1 mRNA

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/804796 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Mohd Fahami Nur Azlina ◽

Yusof Kamisah ◽

Kien Hui Chua ◽

Hj Mohd Saad Qodriyah

Keyword(s):

Mrna Expression ◽

Gastric Acidity ◽

Protective Factor ◽

Water Immersion ◽

Gastric Injury ◽

Control Group ◽

Prostaglandin E ◽

Treatment Groups ◽

Rat Gastric Mucosa ◽

Cox 1

The present study aims to distinguish the effect of tocotrienol on an important gastric protective factor, prostaglandin E2(PGE2), in stress-induced gastric injury. Twenty-eight Wistar rats were divided into four groups of seven rats each. Two control groups were fed commercial rat diet, and two treatment groups were fed the same diet but with additional dose of omeprazole (20 mg/kg) or tocotrienol (60 mg/kg). After 28 days, rats from one control group and both treated groups were subjected to water-immersion restraint stress for 3.5 hours once. The rats were then sacrificed, their stomach isolated and gastric juice collected, lesions examined, and gastric PGE2content and cyclooxygenase (COX) mRNA expression were determined. Both the regimes significantly attenuated the total lesion area in the stomach compared to the control. Gastric acidity, which was increased in stress, was significantly reduced in rats supplemented with omeprazole and tocotrienol. The PGE2content was also significantly higher in the rats given tocotrienol supplementation compared to the control followed by an increase in COX-1 mRNA expression. We conclude that tocotrienol supplementation protected rat gastric mucosa against stress-induced lesions possibly by reducing gastric acidity and preserving gastric PGE2by increasing COX-1 mRNA.

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