Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Opuntia humifusa Raf. (O. humifusa Raf.) is a member of the Cactaceae family. To determine the antioxidative and anti-inflammatory effects of this herb, various solvent fractions (methanol, hexane, chloroform, ethyl acetate, butanol, and water) prepared from the leaves of cacti were tested using DPPH (2,2-diphenyl-l-picrylhydrazyl radical) and xanthine oxidase assays, and nitric oxide (NO)-producing macrophage cells. We found that O. humifusa Raf. displayed potent antioxidative and anti-inflammatory activity. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. The scavenging effect of the ethyl acetate fraction was higher than that of the other fractions, with IC50 values of 3.6 and 48.2 microg mL(-1). According to activity-guided fractionation, one of the active radical scavenging principles in the ethyl acetate fraction was found to be quercetin. In contrast, only two fractions (chloroform and ethyl acetate) significantly suppressed nitric oxide production from the lipopolysaccharide (LPS)-activated RAW264.7 cells. In addition, chloroform and ethyl acetate fractions significantly blocked the expression of inducible nitric oxide synthetase (iNOS) and interleukin-6 (IL-6) from the RAW264.7 cells stimulated by LPS. Moreover, ethyl acetate fractions significantly blocked the expression of IL-1beta from the RAW264.7 cells stimulated by LPS. Therefore, the results suggested that O. humifusa Raf. may modulate radical-induced toxicity via both direct scavenging activity and the inhibition of reactive species generation, and the modulation of the expression of inflammatory cytokines. Finally, O. humifusa Raf. may be useful as a functional food or drug against reactive species-mediated disease.
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PMID:Radical scavenging and anti-inflammatory activity of extracts from Opuntia humifusa Raf. 1639 71

Inflammation and oxidative stress are associated with cancer, atherosclerosis, and other chronic diseases. Dietary flavonoids have been reported to possess antiinflammatory and antioxidant properties, but their mechanisms of action and structure-activity relations have not been fully investigated. We hypothesized that differences in antioxidant activity between the structurally similar flavones, luteolin and chrysin (differing only in B-ring hydroxylation patterns), would differentially affect inflammation-associated Cox-2 expression and PGE2 formation. Pretreatment of RAW 264.7 macrophage-like cells with 25, 50, or 100 micromol/L concentrations of luteolin inhibited lipopolysaccharide (LPS)-induced Cox-2 protein expression (P < 0.0001). Chrysin pretreatment did not reduce LPS-induced Cox-2 protein expression at any level tested. Conversely, both luteolin and chrysin completely suppressed LPS-induced PGE2 formation (P < 0.001). Luteolin, but not chrysin, inhibited xanthine/xanthine oxidase-generated superoxide formation at 100 micromol/L in a cell-free system (P < 0.001). Although both luteolin and chrysin reduced LPS-induced hydroxyl radical formation relative to the positive control (P < 0.001), luteolin was superior to chrysin (P = 0.003). In summary, luteolin and chrysin suppressed PGE2 formation equally well, despite differential effects on Cox-2 protein expression and on superoxide and hydroxyl radical scavenging. These data indicate that flavones may display similar antiinflammatory activity via different mechanisms.
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PMID:Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells. 1670 14

Physalis peruviana L. (PP) is a medicinal herb widely used in folk medicine. In this study, supercritical carbon dioxide (SFE-CO2) method was employed to obtain three different PP extracts, namely SCEPP-0, SCEPP-4 and SCEPP-5. The total flavonoid and phenol concentrations, as well as antioxidant and anti-inflammatory activities of these extracts were analyzed and compared with aqueous and ethanolic PP extracts. Among all the extracts tested, SCEPP-5 demonstrated the highest total flavonoid (234.63+/-9.61 mg/g) and phenol (90.80+/-2.21 mg/g) contents. At concentrations 0.1-30 microg/ml, SCEPP-5 also demonstrated the strongest superoxide anion scavenging activity and xanthine oxidase inhibitory effect. At 30 microg/ml, SCEPP-5 significantly prevented lipopolysaccharide (LPS; 1 microg/ml)-induced cell cytotoxicity in murine macrophage (Raw 264.7) cells. At 10-50 microg/ml, it also significantly inhibited LPS-induced NO release and PGE2 formation in a dose-dependent pattern. SCEPP-5 at 30 microg/ml remarkably blocked the LPS induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Taken together, these results suggest that SCEPP-5, an extract of SFE-CO2, displayed the strongest antioxidant and anti-inflammatory activities as compared to other extracts. Its protection against LPS-induced inflammation could be through the inhibition of iNOS and COX-2 expression.
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PMID:Supercritical carbon dioxide extract exhibits enhanced antioxidant and anti-inflammatory activities of Physalis peruviana. 1682 Feb 75

Chronic hypoxic (CH) preconditioning reduces superoxide-induced renal dysfunction via the upregulation of superoxide dismutase (SOD) activity and contents. Endotoxaemia reduces renal antioxidant status. We hypothesize that CH preconditioning might protect the kidney from subsequent endotoxaemia-induced oxidative injury. Endotoxaemia was induced by intraperitoneal injection of lipopolysaccharide (LPS; 4 mg kg(-1)) in rats kept at sea level (SL) and rats with CH in an altitude chamber (5500 m for 15 h day(-1)) for 4 weeks. LPS enhanced xanthine oxidase (XO) and gp91phox (catalytic subunit of NADPH oxidase) expression associated with burst amount of superoxide production from the SL kidney surface and renal venous blood detected by lucigenin-enhanced chemiluminescence. LPS induced a morphologic-independent renal dysfunction in baseline and acute saline loading stages and increased renal IL-1beta protein and urinary protein concentration in the SL rats. After 4 weeks of induction, CH significantly increased Cu/ZnSOD, MnSOD and catalase expression (16 +/- 17, 128 +/- 35 and 48 +/- 21, respectively) in renal cortex, and depressed renal cortex XO (44 +/- 16%) and renal cortex (20 +/- 9%) and medulla (28 +/- 11%) gp91phox when compared with SL rats. The combined effect of enhanced antioxidant proteins and depressed oxidative proteins significantly reduced LPS-enhanced superoxide production, renal XO and gp91phox expression, renal IL-1beta production, and urinary protein level. CH also ameliorated LPS-induced renal dysfunction in the baseline and acute saline loading periods. We conclude that CH treatment enhances the intrarenal antioxidant/oxidative protein ratio to overcome endotoxaemia-induced reactive oxygen species formation and inflammatory cytokine release.
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PMID:Hypoxic preconditioning attenuates lipopolysaccharide-induced oxidative stress in rat kidneys. 1734 61

Previous work has demonstrated that reactive oxygen intermediates (ROIs) play an important regulatory role in the induction of monocyte chemotactic protein 1 (MCP-1) in certain cells. This study investigated the mechanisms of ROI regulation of MCP-1 gene expression in whole blood and isolated peripheral blood mononuclear cells (PBMCs). The antioxidants dimethyl sulfoxide (DMSO), N-acetyl cysteine, and dimethyl thiourea significantly inhibited lipopolysaccharide (LPS)-induced MCP-1 production in either whole blood or isolated blood cells. In contrast, interleukin 6 and tumor necrosis factor production were not affected and interleukin-1beta levels were actually increased with DMSO treatment. Exogenous ROI (either hydrogen peroxide or O2 generated by xanthine/xanthine oxidase) stimulated MCP-1 production, which was also inhibited by DMSO. To confirm the biological relevance of these findings in vivo, mice treated with DMSO before LPS challenge had significantly lower plasma levels of MCP-1. The level of inhibition was addressed in experiments which demonstrated that DMSO significantly decreased MCP-1 mRNA induced by LPS in whole blood and PBMCs. Cycloheximide treatment did not abolish the DMSO inhibition of MCP-1 mRNA, demonstrating that de novo protein synthesis is not required. Treatment with actinomycin D showed that DMSO did not increase the decay rate of MCP-1 mRNA, indicating that ROI did not change the stability of MCP-1 mRNA. These results provide evidence that in whole blood and PBMCs, DMSO regulates MCP-1 gene expression by decreasing the induction of MCP-1 mRNA.
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PMID:Mechanisms of oxidant regulation of monocyte chemotactic protein 1 production in human whole blood and isolated mononuclear cells. 1752 8

Oxidative stress due to excessive reactive species (RS) and weakened antioxidant defenses is causally associated with inflammation and inflammatory mediators. To investigate the effects of the major fish oil ingredients, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on oxidative stress-related inflammatory status, we conducted in vitro experiments utilizing rat renal epithelial cells (NRK-52E) and murine macrophages (RAW 264.7) by assessing their effects on the generation of cyclooxygenase (COX)-2-derived and xanthine oxidase (XOD)-derived RS, reduced glutathione (GSH) levels, and antioxidative enzyme activities. Additionally, 6-keto-prostaglandin (PG) F1alpha, PGE2, and nitrite levels were measured in lipopolysaccharide-stimulated RAW 264.7 macrophages. Results showed that the generation of RS from arachidonic acid through the COX-2 and XOD pathways was effectively suppressed by DHA and EPA, while GSH levels and antioxidative enzyme activities were significantly enhanced by DHA and EPA. Furthermore, levels of inflammatory mediators (thromboxane B2, PGE2, and 6-keto-PGF1alpha) and nitrite were effectively down-regulated by DHA and EPA. These results strongly indicate that DHA and EPA exert antioxidative and anti-inflammatory actions by reducing the cellular levels of RS, pro-inflammatory mediators, and nitrite levels and by maintaining higher GSH levels and antioxidative enzyme activities.
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PMID:Antioxidative and anti-inflammatory actions of docosahexaenoic acid and eicosapentaenoic acid in renal epithelial cells and macrophages. 1765 Oct 56

Suaeda asparagoides Miq. (Chenopodiaceae: S. asparagoides) is a salt-marsh plant that has long been prescribed in traditional Oriental medicine for the treatment of hypertension and hepatitis. In order to elucidate the pharmacological mechanisms of the herb, we conducted an examination of the anti-oxidative and anti-inflammatory properties of solvent-extracts of S. asparagoides. All of the solvent fractions showed potent anti-oxidative effects, as assessed using a radical generation assay system (xanthine oxidase assay) and an electron-donating activity system (DPPH [2,2-diphenyl-l-picrylhydrazyl radical] assay), with IC50 values ranging from 9 to 42 microg/ml. In agreement with this pattern, the total phenolic contents were widely distributed in the various solvent fractions, and ranged from 36.5 to 50.3 mg/g of dry weight. All of the solvent fractions significantly suppressed NO production in RAW264.7 cells induced by lipopolysaccharide (LPS, 0.1 microg/ml) and of the fractions, only the chloroform (CHC) fraction completely blocked the expression of inducible NO synthase (iNOS). Additionally, the hexane (HEX) and CHC fractions suppressed the mRNA expression of granulocyte/macrophage colony-stimulating factor (GM-CSF) and monocyte chemoattractant protein 1 (MCP-1), respectively, in the LPS-stimulated RAW264.7 cells. Therefore, these results suggest that the pharmacological action of S. asparagoides is due to its potent anti-oxidative effects and anti-inflammatory effects, and that therefore it can be applied to other diseases caused by oxidative stress and inflammation, such as cardiovascular diseases.
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PMID:In vitro anti-oxidative and anti-inflammatory effects of solvent-extracted fractions from Suaeda asparagoides. 1766 94

We recently reported that in vitro Cognac polyphenolic compounds (CPC) induce NO-dependent vasorelaxant effects and stimulate cardiac function. In the present study, we aim to investigate the effect of CPC on both nitric oxide (NO) and superoxide anions (O(2)(-)) production in cultured human endothelial cells. In addition, its effect on the bradykinin (BK)-induced NO production was also tested. The role and sources of O(2)(-) in the concomitant effect of BK plus CPC were pharmacologically determined. NO and O(2)(-) signals were measured using electron paramagnetic resonance technique using specific spin trappings. Both, CPC and BK induced an increase in NO production in human endothelial cells. The combination of both further enhanced NO release. The capacity of CPC plus BK to increase NO signal was blunted by the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester, and was enhanced in the presence either of superoxide dismutase or catalase. Moreover, CPC plus BK response was greater after inhibition of either NADPH oxidase by apocynin or xanthine oxidase by allopurinol but it was not affected by rotenone. CPC did not affect O(2)(-) level either alone or after its increase upon lipopolysaccharide treatment. Finally, the capacity of BK alone to increase NO was enhanced either by apocynin or allopurinol. Altogether, these data demonstrate that CPC is able to directly increase NO production without affecting O(2)(-) and enhances the BK-induced NO production in human endothelial cells. The data highlight the ability of BK to stimulate not only NADPH oxidase- but also xanthine oxidase-inhibitor sensitive mechanisms that reduce its efficiency in increasing NO either alone or in the presence of CPC. These results bring pharmacological evidence for vascular protection by CPC via its potentiating effect of BK response in terms of endothelial NO release.
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PMID:Cognac polyphenolic compounds increase bradykinin-induced nitric oxide production in endothelial cells. 1805 79

Redox regulation of inducible nitric oxide synthase (iNOS) expression was investigated in lipopolysaccharide and interferon-gamma (LPS + IFNgamma)-stimulated microvascular endothelial cells from mouse skeletal muscle. Unstimulated endothelial cells produced reactive oxygen species (ROS) sensitive to inhibition of NADPH oxidase (apocynin and DPI), mitochondrial respiration (rotenone) and NOS (L-NAME). LPS + IFNgamma caused a marked increase in ROS production; this increase was abolished by inhibition of NADPH oxidase (apocynin, DPI and p47phox deficiency). LPS + IFNgamma induced substantial expression of iNOS protein. iNOS expression was prevented by the antioxidant ascorbate and by NADPH oxidase inhibition (apocynin, DPI and p47phox deficiency), but not by inhibition of mitochondrial respiration (rotenone) and xanthine oxidase (allopurinol). iNOS expression also was prevented by selective antagonists of ERK, JNK, Jak2, and NFkappaB activation. LPS + IFNgamma stimulated activation/phosphorylation of ERK, JNK, and Jak2 and activation/degradation of IkappaB, but only the activation of JNK and Jak2 was sensitive to ascorbate, apocynin and p47phox deficiency. Ascorbate, apocynin and p47phox deficiency also inhibited the LPS + IFNgamma-induced DNA binding activity of transcription factors IRF1 and AP1 but not NFkappaB. In conclusion, LPS + IFNgamma-induced NFkappaB activation is necessary for iNOS induction but is not dependent on ROS signaling. LPS + IFNgamma-stimulated NADPH oxidase activity produces ROS that activate the JNK-AP1 and Jak2-IRF1 signaling pathways required for iNOS induction. Since blocking either NFkappaB activation or NADPH oxidase activity is sufficient to prevent iNOS expression, they are separate targets for therapeutic interventions that aim to modulate iNOS expression in sepsis.
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PMID:iNOS expression requires NADPH oxidase-dependent redox signaling in microvascular endothelial cells. 1848 Dec 58

In an effort to develop novel anti-tumor, or cancer chemopreventive agents, a series of 2',5'-dialkoxylchalcones were prepared by Claisen-Schmidt condensation of appropriate acetophenones with suitable aromatic aldehyde. In vitro screening revealed low micromolar activity (IC(50)) against several human cancer cell lines. Selective compound 10 induced an accumulation of A549 cells in the G(2)/M phase arrest which was well correlated with inhibitory activity against tubulin polymerization. Cytotoxic compounds 3 and 12 showed significant inhibitory effects on NO production in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage-like cells while cytotoxic compound 10 revealed potent inhibitory effect on TNF-alpha formation in RAW 264.7 cells in response to LPS. Compounds 3 and 10 also showed significant inhibitory effects on xanthine oxidase. The present results suggested that compounds 3 and 10 were potential to be served as cancer chemopreventive agents.
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PMID:Synthesis and cytotoxic, anti-inflammatory, and anti-oxidant activities of 2',5'-dialkoxylchalcones as cancer chemopreventive agents. 1860 46


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