Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The process of degranulation of mast cells and neutrophils contributes to inflammatory disorders. Activation of microglial cells and macrophages is believed to be involved in inflammatory, infectious and degenerative diseases of the CNS. Combining the potent inhibition of chemical mediators released by the degranulation of mast cells or neutrophils and from the activated microglial cells or macrophages, would lead to a promising anti-inflammatory agent for the treatment of peripheral and central inflammation. A series of chalcone derivatives have been reported to have potent anti-inflammatory activity. In an effort to continually develop potent anti-inflammatory agents, novel series of chalcones, 2'-hydroxy- and 2',5'-dihydroxychalcones were synthesized and their inhibitory effects on the activation of mast cells, neutrophils, microglial cells and macrophages were evaluated in-vitro. The chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with an appropriate aromatic aldehyde. The alkoxychalcones were prepared with appropriate hydroxychalcones and alkyl iodide and the dihydroxychalcones were prepared by hydrogenation of an appropriate chalcone with Pd/C. Almost all of the hydroxychalcones exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Of the hydroxychalcones, compound 1 was the most potent inhibitor of the release of beta-glucuronidase (IC50=1.6+/-0.2 microM) and lysozyme (IC50=1.4+/-0.2 microM) from rat neutrophils stimulated with fMLP/CB. Almost all of the 2',5'-dialkoxychalcones exhibited potent inhibitory effects on nitric oxide (NO) formation from murine microglial cell lines N9 stimulated with lipopolysaccharide (LPS). Of these, compound 11 showed the greatest effect (IC50=0.7+/-0.06 microM). The present results demonstrated that most of the chalcone derivatives have an anti-inflammatory effect. The inhibitory effects of dialkoxychalcones, 10-12 on inflammation are probably not due to the inhibition of mast cells and neutrophil degranulation, but are mediated through the suppression of NO formation from N9 cells.
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PMID:Synthesis and anti-inflammatory effect of chalcones. 1071 46

The anti-inflammatory activities of the isolated flavonoids, quercetin 3-O-methyl ether (1), kaempferol (2), and quercetin (3), of Rhamnus nakaharai, and anthraquinone, frangulin B (4), of Rhamnus formosana, were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells, neutrophils, macrophages, and microglial cells. Compounds 1 - 3 strongly inhibited the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB). Compound 1 strongly inhibited superoxide anion formation in fMLP/CB or phorbol 12-myristate 13-acetate (PMA)-stimulated rat neutrophils. Compound 1 exhibited potent inhibitory effect on tumor-necrosis factor-alpha ( TNF-alpha) formation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells while 1 and 4 showed potent inhibitory effects on TNF-alpha formation in LPS/IFN-gamma (interferon-gamma)-stimulated murine microglial cell lines N9.
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PMID:In vitro anti-inflammatory effects of quercetin 3-O-methyl ether and other constituents from Rhamnus species. 1173 18

Two new pentaoxygenated xanthones, 2,3-dihydroxy-1,6,7-trimethoxyxanthone (1) and 3,6-dihydroxy-1,5,7-trimethoxyxanthone (2) were isolated from the leaf of Hypericum geminiflorum. The antiplatelet activities of the constituents, 2,6-dimethoxy-p-benzoquinone (3), gemichalcone A (4), gemichalcone B (5), and cycloartocarpin (6), of this plant, were assessed in vitro by determining their inhibitory effects on the aggregation of washed rabbit platelets induced by various inducers. The anti-inflammatory effects of 4 and 5 were assessed in vitro by determining their inhibitory effects on the chemical mediators released from mast cells and neutrophils. Of the compounds tested, 4 exhibited the most potent inhibition of platelet aggregation induced by arachidonic acid (AA) and 4 and 5 strongly inhibited the release of beta-glucuronidase and lysozyme in formyl-Met-Leu-Phe (fMLP)-stimulated rat neutrophils.
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PMID:Antiplatelet and anti-inflammatory constituents and new oxygenated xanthones from Hypericum geminiflorum. 1184 22

Azurophil granules of neutrophils beyond their already known heterogeneity of beta-glucuronidase and myeloperoxidase enzyme contents are heterogeneous with respect to a spontaneous or low concentration (2.3 or 23 nM) of formyl-Met-Leu-Phe-induced mobilization. This suggests that the heterogeneity of azurophil granules is manifested in their functions too.
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PMID:Azurophil granules are heterogeneous with respect to mobilization induced by different concentrations of fMLP. 1185 80

Some chalcones exert potent anti-inflammatory activities. 2',5'-Dialkoxychalcones and 2',5'-dihydroxy-4-chloro-dihydrochalcone inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma)-activated N9 microglial cells and in LPS-activated RAW 264.7 macrophage-like cells have been demonstrated in our previous reports. These compounds also suppressed the inducible NO synthase (iNOS) expression and cyclooxygenase-2 (COX-2) activity in RAW 264.7 cells. In an effort to continually develop potent anti-inflammatory agent, a series of chalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with appropriate aromatic aldehyde and then evaluated their inhibitory effects on the activation of mast cells, neutrophils, macrophages, and microglial cells. Most of the 2',5'-dihydroxychaclone derivatives exhibited potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). Some chalcones showed potent inhibitory effects on superoxide anion generation in rat neutrophils in response to fMLP/CB. Compounds 1 and 5 exhibited potent inhibitory effects on NO production in macrophages and microglial cells. Compound 11 showed inhibitory effect on NO production and iNOS protein expression in RAW 264.7 cells. The present results demonstrated that most of the 2',5'-dihydroxychaclones have anti-inflammatory effects. The potent inhibitory effect of 2',5'-dihydroxy-dihydrochaclones on NO production in LPS-activated macrophage, probably through the suppression of iNOS protein expression, is proposed to be useful for the relief of septic shock.
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PMID:Structure-activity relationship studies on chalcone derivatives. the potent inhibition of chemical mediators release. 1246 13

The transient expression of three novel plant amber suppressors derived from a cloned Nicotiana tRNA(Ser)(CGA), an Arabidopsis intron-containing tRNA(Tyr)(GTA) and an Arabidopsis intron-containing tRNA(Met)(CAT) gene, respectively, was studied in a homologous plant system that utilized the Agro bacterium-mediated gene transfer to Arabidopsis hypocotyl explants. This versatile system allows the detection of beta-glucuronidase (GUS) activity by histochemical and enzymatic analyses. The activity of the suppressors was demonstrated by the ability to suppress a premature amber codon in a modified GUS gene. Co-transformation of Arabidopsis hypocotyls with the amber suppressor tRNA(Ser) gene and the GUS reporter gene resulted in approximately 10% of the GUS activity found in the same tissue transformed solely with the functional control GUS gene. Amber suppressor tRNAs derived from intron-containing tRNA(Tyr) or tRNA(Met) genes were functional in vivo only after some additional gene manipulations. The G3:C70 base pair in the acceptor stem of tRNA(Met)(CUA) had to be converted to a G3:U70 base pair, which is the major determinant for alanine tRNA identity. The inability of amber suppressor tRNA(Tyr) to show any activity in vivo predominantly results from a distorted intron secondary structure of the corresponding pre-tRNA that could be cured by a single nucleotide exchange in the intervening sequence. The improved amber suppressors tRNA(Tyr) and tRNA(Met) were subsequently employed for studying various aspects of the plant-specific mechanism of pre-tRNA splicing as well as for demonstrating the influence of intron-dependent base modifications on suppressor activity.
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PMID:Translational nonsense codon suppression as indicator for functional pre-tRNA splicing in transformed Arabidopsis hypocotyl-derived calli. 1258 39

One new pterocarpanoid, crotafuran E (1), and three known compounds were isolated from the bark of Crotalaria pallida. The structure of 1 was determined by spectral methods. Two pterocarpanoids, crotafurans A (2) and B (3), previously isolated from this plant, showed significant concentration-dependent inhibitory effects on the NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage-like cells, with IC(50) values of 23.0 +/- 1.0 and 19.0 +/- 0.2 microM, respectively. Compound 3 also inhibited the LPS/interferon-gamma (IFN-gamma)-stimulated NO production in N9 microglial cells with an IC(50) value of 9.4 +/- 0.9 microM. Moreover, compound 2 produced a concentration-dependent inhibition of the release of beta-glucuronidase and lysozyme from rat neutrophils in response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB) with IC(50) values of 7.8 +/- 1.4 and 9.5 +/- 2.1 microM, respectively.
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PMID:Anti-inflammatory constituents and new pterocarpanoid of Crotalaria pallida. 1266 1

Four novel phloroglucinol derivatives, garcinielliptones A (1), B (2), C (3), D (4), a novel triterpenoid, garcinielliptone E (5), and three known compounds were isolated from the seeds of Garcinia subelliptica. The structures, including relative configurations, were elucidated by means of spectroscopic data. Known compounds garsubellin A (6) and garcinielliptin oxide (7) showed potent inhibitory effects on the release of beta-glucuronidase, and beta-glucuronidase and histamine, respectively, from peritoneal mast cells stimulated with compound 48/80 in a concentration-dependent manner with IC(50) values of 15.6+/-2.5, and 18.2+/-3.6 and 20.0+/-2.7 microM, respectively. Compound 7 showed potent inhibitory effects on the release of beta-glucuronidase and lysozyme from neutrophils stimulated with formyl-Met-Leu-Phe(fMLP)/cytochalasin B (CB) in a concentration-dependent manner with IC(50) values of 15.7+/-3.0 and 23.9+/-3.2 microM, respectively. Compound 7 also showed potent inhibitory effect on superoxide formation from neutrophils stimulated with fMLP/CB also in a concentration-dependent manner with an IC(50) value of 17.9+/-1.5 microM.
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PMID:Novel and anti-inflammatory constituents of Garcinia subelliptica. 1274 Aug 42

Three novel phloroglucinol derivatives, garcinielliptones F (1), H (3), and I (4), and two novel terpenoids, garcinielliptones G (2) and J (5), with a new skeleton have been isolated from the seeds of Garcinia subelliptica. Their structures, including relative configurations, were elucidated by spectroscopic methods and computer-generated molecular modeling. Compound 1 showed potent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils that had been stimulated with formyl-Met-Leu-Phe (fMLP)/cytochalasin B (CB). This effect was concentration-dependent with IC(50) values of 26.9+/-2.6 and 20.0+/-1.3 microM, respectively. Compound 1 also showed a potent concentration-dependent inhibitory effect on superoxide anion generation in rat neutrophils stimulated with fMLP/CB, with an IC(50) value of 17.0+/-0.9 microM. Compound 4 showed a potent inhibitory effect on NO production in culture media of N9 cells in response to lipopolysaccharide (LPS)/interferon-gamma (IFN-gamma) in a concentration-dependent manner with an IC(50) value of 7.4+/-0.2 microM.
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PMID:Terpenoids with a new skeleton and novel triterpenoids with anti-inflammatory effects from Garcinia subelliptica. 1463 35

One new isoflavone, 5,7,4'-trihydroxy-2'-methoxyisoflavone (3) and seven, and four known compounds were isolated from the barks of Crotalaria pallida and the seeds of C. assamica, respectively. The known compounds, apigenin (1) and 2'-hydroxygenistein (2), isolated from C. pallida, showed significant concentration-dependent inhibitory effects on the release of beta-glucuronidase and lysozyme from rat neutrophils in response to formyl-Met-Leu-Phe/cytochalasin B (fMLP/CB) with IC(50) values of 2.8+/-0.1 and 17.7+/-1.9, and 5.9+/-1.4 and 9.7+/-3.5 microM, respectively. The known compounds, daidzein (4) and 2'-hydroxydaidzein (6), isolated from C. pallida, inhibited of the release of lysozyme and beta-glucuronidase from rat neutrophils in response to fMLP/CB with IC(50) values of 26.3+/-5.5 and 13.7+/-2.6 microM, respectively. Compounds 1 and 4 also showed significant concentration-dependent inhibitory effects on superoxide anion generation in rat neutrophils stimulated with fMLP/CB with IC(50) values of 3.4+/-0.3 and 25.1+/-5.0 microM, respectively. Compounds 1 and 5, previously isolated from C. pallida, showed the inhibition of NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and LPS/interferon-gamma (IFN-gamma)-stimulated N9 microglial cells with IC(50) values of 10.7+/-0.1 and 13.9+/-1.1 microM, respectively. Flavonoids, suppressed chemical mediators in inflammatory cells, may have value in treatment and prevention of central and peripheral inflammatory diseases associated with excess production of chemical mediators.
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PMID:Anti-inflammatory flavonoids and pterocarpanoid from Crotalaria pallida and C. assamica. 1501 12


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