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COX-2 Enzyme (cox-2 + enzyme)

Distribution by Scientific Domains

Medical Sciences	50%
Chemistry	50%

Selected Abstracts

Insulin Secretagogues from Moringa oleifera with Cyclooxygenase Enzyme and Lipid Peroxidation Inhibitory Activities

HELVETICA CHIMICA ACTA, Issue 2 2004
Jayaraj
Bioassay-directed isolation and purification of the methanol extract of Moringa oleifera fruits yielded bioactive N -benzyl thiocarbamates, N -benzyl carbamates, benzyl nitriles, and a benzyl ester. Among these, methyl 2-[4-(, - L -rhamnopyranosyl)phenyl]acetate (2), N -[4-(, - L -rhamnopyranosyl)benzyl]-1- O - , - D -glucopyranosylthiocarboxamide (3), 1- O -phenyl- , - L -rhamnopyranoside (5), and 4-[(, - D -glucopyranosyl)-(1,3)-(, - L -rhamnopyranosyl)]phenylacetonitrile (6) are novel, and their structures were determined by spectroscopic methods. The known compounds isolated and characterized from the MeOH extract were niazirin (=4-(, - L -rhamnopyranosyl)phenylacetonitrile; 1), niazicin A (=methyl N -{4-[(4,- O -acetyl- , - L -rhamnopyranosyl)benzyl]}thiocarbamate; 4), methyl N -{4-[(, - L -rhamnopyranosyl)benzyl]}carbamate (7), and methyl N -{4-[(4,- O -acetyl- , - L -rhamnopyranosyl)benzyl]}carbamate (8). The combined yield of these compounds from dried M. oleifera fruits was 1.63%. In rodent pancreatic , -cells (INS-1), compounds 4, 5, 6, 7, and 8 at 100,ppm significantly stimulated insulin release. Cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme inhibition assays revealed that 5 and 6 were most active at 83,ppm. Compound 6, however, demonstrated greater specificity for inhibition of COX-2 enzyme (46%) than COX-1 enzyme. Lipid peroxidation assays revealed that 4 and 6 at 50,ppm inhibited peroxidation reactions by 80 and 95%, respectively, while 3 and 8 inhibited lipid peroxidation by 35%. These compounds did not inhibit the cell growth when tested with human breast (MCF-7), central nervous system (CNS, SF-268), lung (NCI-H460), or colon (HCT-116) cancer cell lines. Moreover, these compounds were not cytotoxic at the concentrations tested. [source]

Byakangelicol, isolated from Angelica dahurica, inhibits both the activity and induction of cyclooxygenase-2 in human pulmonary epithelial cells

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2002
C. H. Lin
ABSTRACT We examined the inhibitory mechanism of byakangelicol, isolated from Angelica dahurica, on interleukin-1, (IL-1,)-induced cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) release in human pulmonary epithelial cell line (A549). Byakangelicol (10,50 ,m) concentration-dependently attenuated IL-1,-induced COX-2 expression and PGE2 release. The selective COX-2 inhibitor, NS-398 (0.01,1 ,m), and byakangelicol (10,50 ,m) both concentration-dependently inhibited the activity of the COX-2 enzyme. Byakangelicol, at a concentration up to 200 ,m, did not affect the activity and expression of COX-1 enzyme. IL-1,-induced p44/42 mitogen-activated protein kinase (MAPK) activation was inhibited by the MAPK/extracellular signal-regulated protein kinase (MEK) inhibitor, PD 98059 (30 ,m), while byakangelicol (50 ,m) had no effect. Treatment of cells with byakangelicol (50 ,m) or pyrrolidine dithiocarbamate (PDTC; 50 ,m) partially inhibited IL-1,-induced degradation of 1,B-, in the cytosol, translocation of p65 NF-,B from the cytosol to the nucleus and the NF-,B-specific DNA-protein complex formation. Taken together, we have demonstrated that byakangelicol inhibits IL-1,-induced PGE2 release in A549 cells; this inhibition may be mediated by suppression of COX-2 expression and the activity of COX-2 enzyme. The inhibitory mechanism of byakangelicol on IL-1,-induced COX-2 expression may be, at least in part, through suppression of NF-,B activity. Therefore, byakangelicol may have therapeutic potential as an anti-inflammatory drug on airway inflammation. [source]

Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation

PHYTOTHERAPY RESEARCH, Issue 7 2009
Vanisree Mulabagal
Abstract Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 µm with no activity against COX-1 enzyme. The IC50 values of compound 1 against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74,3.63 µm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF- ,B activation when tested at 100 µm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF- ,B activation for compounds 1 and 2. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Detection of Overexpressed COX-2 in Precancerous Lesions of Hamster Pancreas and Lungs by Molecular Imaging: Implications for Early Diagnosis and Prevention

CHEMMEDCHEM, Issue 6 2006
Hildegard
Abstract The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovascular mortality in long-term users of the COX-2 inhibitors Vioxx and Celebrex, emphasizing the need for noninvasive tests that allow the identification of individuals whose COX-2 levels are overexpressed prior to assignment to treatment with these drugs. In this study, we have prepared a radioiodinated analogue of the selective COX-2 inhibitor celecoxib, and verified its binding to the COX-2 enzyme in,vitro. Biodistribution studies in hamsters demonstrated significantly higher levels of radiotracer in animals treated with the tobacco carcinogen NNK in lung, pancreas, and liver. Assessment of COX-2 levels by whole-body planar nuclear imaging two hours after injection of the radiotracer was suggestive of a distinct increase in COX-2 in the pancreas and liver of a hamster treated for 10 weeks with NNK, in the lungs and liver of a second animal, and in the liver only, in two additional animals from the same treatment group. Immunostains showed selective overexpression of COX-2 in pre-neoplastic lesions of the pancreas and lungs in only those animals that showed tracer accumulation in these organs and in the livers of all NNK-treated hamsters. Immunostains for COX-1 yielded detectable reactions in the intestinal epithelium but not in pancreas, lungs, or liver, supporting the specificity of the tracer for COX-2. Our data provide proof of principle for the hypothesis that molecular imaging with radiolabeled COX-2 inhibitors can be used for the noninvasive monitoring of overexpressed COX-2 levels. [source]