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1.
China Journal of Chinese Materia Medica ; (24): 148-159, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970510

RESUMO

A hyperuricemic rat model induced by adenine and ethambutol was established to investigate the anti-hyperuricemia activity and its mechanism of the flavonoid extract from saffron floral bio-residues. Sixty-seven SD rats were randomly divided into control group, model group, positive control group, and flavonoid extract groups(with 3 doses), respectively, and each group contained 11 or 12 rats. The hyperuricemic model was established by continuous oral administration of adenine(100 mg·kg~(-1)) and ethambutol(250 mg·kg~(-1)) for 7 days. At the same time, the positive control group was given allopurinol(20 mg·kg~(-1) per day) and the flavonoid extract groups were given the flavonoid extract at doses of 340, 170 and 85 mg·kg~(-1) per day, respectively. On day 8, rat serum, liver, kidney, and intestinal tissues were collected, and the levels of uric acid in serum and tissue, the xanthine oxidase activities and antioxi-dant activities in serum and liver were evaluated, and the kidney histopathology was explored. In addition, an untargeted serum metabolomics study was performed. According to the results, the flavonoid extract effectively reduced the uric acid levels in serum, kidney and ileum and inhibited the xanthine oxidase activities and elevated the antioxidant activities of serum and liver in hyperuricemic rat. At the same time, it reduced the levels of inflammation factors in kidney and protected renal function. Moreover, 68 differential metabolites of hyperuricemic rats were screened and most of which were lipids and amino acids. The flavonoid extract significantly retrieved the levels of differential metabolites in hyperuricemic rats, such as SM(d18:1/20:0), PC[18:0/18:2(92,12Z)], palmitic acid and citrulline, possibly through the following three pathways, i.e., arginine biosynthesis, glycine, serine and threonine metabolism, and histidine metabolism. To sum up, the flavonoid extract of saffron floral bio-residues lowered the uric acid level, increased the antioxidant activity, and alleviated inflammatory symptoms of hyperuricemic rats, which may be related to its inhibition of xanthine oxidase activity and regulation of serum lipids and amino acids metabolism.


Assuntos
Ratos , Animais , Flavonoides/farmacologia , Ácido Úrico , Crocus , Xantina Oxidase , Etambutol/efeitos adversos , Ratos Sprague-Dawley , Hiperuricemia/tratamento farmacológico , Rim , Antioxidantes/farmacologia , Extratos Vegetais/efeitos adversos , Aminoácidos , Adenina/efeitos adversos , Lipídeos
2.
Philippine Journal of Health Research and Development ; (4): 31-40, 2022.
Artigo em Inglês | WPRIM | ID: wpr-987604

RESUMO

Background@#One of the causes of inflammatory arthritis is excessive production of uric acid or hyperuricemia. It is a painful disease that is treated with a commercial xanthine oxidase inhibitor to decrease uric acid synthesis. However, the treatment is associated with adverse side effects and thus, there is interest in medicinal plants that could have similar therapeutic effects with minimal side effects. There are many reported indigenous plants and trees in the Philippines that are reported to have therapeutic and bioactive compounds. One such plant is Canarium ovatum or locally called pili. This study aimed to determine the antihyperuricemic activity of the ethanolic extract of the leaves of C. ovatum. @*Objective@#Determine the antihyperuricemic activity of the crude ethanolic extract of C. ovatum leaves and its partially purified fractions through inhibition of xanthine oxidase and its effect on the blood uric acid level of oxonate-induced hyperuricemic mice. @*Methodology@#The crude ethanol extract from C. ovatum leaves and its partially purified fractions obtained through column chromatography were tested for their in vitro xanthine oxidase (XO) inhibitory activity by measuring spectrophotometrically the uric acid formation from xanthine as the substrate. The crude ethanol extract and the fraction with the most XO inhibitory activity were then tested for their in vivo XO inhibitory activity in oxonate-induced hyperuricemic mice by measuring their blood uric acid levels using uric acid test strips. @*Results@#The crude ethanolic extract of C. ovatum leaves at 100ppm showed 83.62±2.05% in vitro inhibition of XO while the most active fraction showed 80.30±4.00% inhibition. Both were comparable (p>0.05) to the positive control, allopurinol, which showed 91.47±5.64% inhibition. In vivo, the crude extract and the fraction that showed the highest XO inhibitory activity at 200 mg/kg significantly (p<0.01 and p<0.05) respectively reduced the serum uric acid levels of the hyperuricemic mice one hour after induction as compared to the negative control. Moreover, their antihyperuricemic activity were not statistically significant as compared to that of allopurinol (p<0.0001). @*Conclusion@#The crude ethanolic extract of C. ovatum leaves and its most active fraction showed statistically significant in vitro xanthine oxidase inhibition and in vivo antihyperuricemic activity. The activities shown by both crude and active fraction were not statistically different from that determined for allopurinol. Therefore, further studies can be conducted to isolate the most active compound and study its pharmacokinetic properties.


Assuntos
Xantina Oxidase , Ácido Úrico , Alopurinol
3.
China Journal of Chinese Materia Medica ; (24): 972-979, 2022.
Artigo em Chinês | WPRIM | ID: wpr-928016

RESUMO

The present study analyzed and identified the chemical constituents from ethyl acetate(EA) extract of Taxilli Herba with UPLC-Q-Exactive-MS and screened active xanthine oxidase(XO) inhibitors with HPLC. The analysis was performed on an Hypersil GOLD C_(18) reversed-phase column(2.1 mm×50 mm, 1.9 μm), with the mobile phase of water containing 1% formic acid(A) and methanol(B) under gradient elution, the flow rate of 0.3 mL·min~(-1), and the injection volume of 5 μL. ESI source was used for MS and the compounds were collected in positive and negative ion modes. Xcalibur 4.1 was used to analyze the retention time, accurate relative molecular weight, and fragmentation of the compounds. The inhibitory activity of some known compounds on XO was screened by HPLC. Thirty chemical constituents were identified, including phenolic acids and flavonoids by experimental data combined with information of standards, data reported previously, and databases, such as MzCloud and ChemSpider. The activities of 10 chemical components were screened. Gallic acid and naringenin chalcone had strong inhibitory activities on XO with IC_(50) of 57 μg·mL~(-1) and 108 μg·mL~(-1). UPLC-Q-Exactive-MS allows the accurate, rapid, and comprehensive identification of main chemical constituents from Taxilli Herba. Gallic acid and naringenin chalcone may be the active components of XO inhibitors.


Assuntos
Acetatos , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas em Tandem , Xantina Oxidase
4.
China Journal of Chinese Materia Medica ; (24): 1822-1831, 2021.
Artigo em Chinês | WPRIM | ID: wpr-879097

RESUMO

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.


Assuntos
Cromatografia Líquida , Chrysanthemum , Flavonoides , Cinética , Preparações Farmacêuticas , Espectrometria de Massas em Tandem , Xantina Oxidase/metabolismo
5.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 145-148, 2019.
Artigo em Inglês | WPRIM | ID: wpr-776899

RESUMO

In the present study, two new acetylene conjugate compounds, dibutyl (2Z, 6Z)-octa-2, 6-dien-4-yne dioate (1), and dibutyl (2E, 6E)- octa-2, 6-dien-4-yne dioate (2), were isolated from the dry stem leaves of Viscum album, along with nine known compounds (3 - 11). Their structures were confirmed on the basis of spectroscopic data. Compounds 1 and 8 showed antioxidant activity against xanthine oxidase (XOD) and 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydroxyl (DPPH), with the IC of 1.22 and 1.33 μmol·L, and the SC of 4.34 and 8.22 μmol·L, respectively.


Assuntos
Acetileno , Química , Antioxidantes , Química , Farmacologia , Compostos de Bifenilo , Química , Estrutura Molecular , Picratos , Química , Extratos Vegetais , Química , Farmacologia , Folhas de Planta , Química , Viscum album , Química , Xantina Oxidase , Química
6.
Braz. j. med. biol. res ; 51(5): e6129, 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-889073

RESUMO

Reactive oxygen species and lipid peroxidation are important factors that contribute to the development of age-related cataract. The study included 130 patients with age-related cataract, 69 of whom were diagnosed with hypertension (HT), 20 with hypertension and type 2 diabetes mellitus (DM), and 41 had no accompanying condition. The following parameters were measured in the serum of the examinees: products of lipid peroxidation malondialdehyde (MDA) and lipofuscin-like fluorophores (LLF), activity of prooxidative enzymes xanthine oxidase (XO) and myeloperoxidase (MPO), antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the concentration of thiol groups, and the ferric reducing activity of plasma. The activity of prooxidative enzymes XO and MPO was higher in the plasma of patients with HT (XO=9.0±1.2 U/L; MPO=77.3±8.4 U/L) and with HT and DM (XO=11.9±0.9 U/L; MPO=89.5±5.0 U/L) compared to patients with age-related cataract (XO=6.2±0.9 U/L; MPO=52.4±6.3 U/L; P<0.01). Our research has shown that patients with age-related cataract and hypertension were exposed to increased oxidative damage of biomolecules, based on the increased plasma LLF and MDA content and decreased levels of thiol groups. Oxidative changes of biomolecules in these patients were associated with increased activity of the XO, MPO, and GPx enzymes and a lower extracellular SOD activity and total ferric reductive ability of plasma.


Assuntos
Humanos , Masculino , Idoso , Xantina Oxidase/metabolismo , Catarata/enzimologia , Diabetes Mellitus Tipo 2/enzimologia , Hipertensão/enzimologia , Xantina Oxidase/sangue , Catarata/complicações , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Hipertensão/complicações
7.
International Journal of Oral Biology ; : 209-216, 2018.
Artigo em Coreano | WPRIM | ID: wpr-740082

RESUMO

Reactive oxygen species (ROS) and nitrogen species (RNS) are involved in cellular signaling processes as a cause of oxidative stress. According to recent studies, ROS and RNS are important signaling molecules involved in pain transmission through spinal mechanisms. In this study, a patch clamp recording was used in spinal slices of rats to investigate the action mechanisms of O₂˙⁻ and NO on the excitability of substantia gelatinosa (SG) neuron. The application of xanthine and xanthine oxidase (X/XO) compound, a ROS donor, induced inward currents and increased the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in slice preparation. The application of S-nitroso-N-acetyl-DLpenicillamine (SNAP), a RNS donor, also induced inward currents and increased the frequency of sEPSC. In a single cell preparation, X/XO and SNAP had no effect on the inward currents, revealing the involvement of presynaptic action. X/XO and SNAP induced a membrane depolarization in current clamp conditions which was significantly decreased by the addition of thapsigargin to an external calcium free solution for blocking synaptic transmission. Furthermore, X/XO and SNAP increased the frequency of action potentials evoked by depolarizing current pulses, suggesting the involvement of postsynaptic action. According to these results, it was estblished that elevated ROS and RNS in the spinal cord can sensitize the dorsal horn neurons via pre- and postsynaptic mechanisms. Therefore, ROS and RNS play similar roles in the regulation of the membrane excitability of SG neurons.


Assuntos
Animais , Humanos , Ratos , Potenciais de Ação , Cálcio , Potenciais Pós-Sinápticos Excitadores , Membranas , Neurônios , Óxido Nítrico , Nitrogênio , Estresse Oxidativo , Células do Corno Posterior , Espécies Reativas de Oxigênio , Medula Espinal , Substância Gelatinosa , Superóxidos , Transmissão Sináptica , Tapsigargina , Doadores de Tecidos , Xantina , Xantina Oxidase
8.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 347-353, 2018.
Artigo em Inglês | WPRIM | ID: wpr-812396

RESUMO

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (-) ethyl 1, 4-di-O-caffeoylquinate (1) and (-) methyl 1, 4-di-O-caffeoylquinate (2), together with 35 known compounds (3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1 (IC 11.94 μmol·L) and 2 (IC 15.04 μmol·L) showed a good inhibitory activity. The current results supported the medical use of the plant.


Assuntos
Adenina , Química , Medicamentos de Ervas Chinesas , Química , Farmacologia , Ativação Enzimática , Flavonoides , Química , Gnaphalium , Química , Supressores da Gota , Química , Farmacologia , Hidroxibenzoatos , Química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Compostos Fitoquímicos , Química , Farmacologia , Componentes Aéreos da Planta , Química , Extratos Vegetais , Química , Farmacologia , Ácido Quínico , Química , Xantina Oxidase
9.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 347-353, 2018.
Artigo em Inglês | WPRIM | ID: wpr-773607

RESUMO

Gnaphalium affine D. Don, a medicinal and edible plant, has been used to treat gout in traditional Chinese medicine and popularly consumed in China for a long time. A detailed phytochemical investigation on the aerial part of G. affine led to the isolation of two new esters of caffeoylquinic acid named (-) ethyl 1, 4-di-O-caffeoylquinate (1) and (-) methyl 1, 4-di-O-caffeoylquinate (2), together with 35 known compounds (3-37). Their structures were elucidated by spectroscopic data and first-order multiplet analysis. All the isolated compounds were tested for their xanthine oxidase inhibitory activity with an in vitro enzyme inhibitory screening assay. Among the tested compounds, 1 (IC 11.94 μmol·L) and 2 (IC 15.04 μmol·L) showed a good inhibitory activity. The current results supported the medical use of the plant.


Assuntos
Adenina , Química , Medicamentos de Ervas Chinesas , Química , Farmacologia , Ativação Enzimática , Flavonoides , Química , Gnaphalium , Química , Supressores da Gota , Química , Farmacologia , Hidroxibenzoatos , Química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Compostos Fitoquímicos , Química , Farmacologia , Componentes Aéreos da Planta , Química , Extratos Vegetais , Química , Farmacologia , Ácido Quínico , Química , Xantina Oxidase
10.
Clinical Nutrition Research ; : 126-135, 2018.
Artigo em Inglês | WPRIM | ID: wpr-713977

RESUMO

The prevalence of gout is increasing worldwide, and control of serum uric acid level has been regarded as one of the therapeutic methods for gout. Inhibition of xanthine oxidase (XO) activity which can oxidize hypoxanthine to uric acid has been commonly proposed to decrease serum uric acid level. The aim of this study was to demonstrate the hypouricemic effect of ethanol extract of Aster glehni leaves (EAG) by in vitro and in vivo study in potassium oxonate (PO)-induced hyperuricemic rats. EAG possessed 132.5 ± 6.8 mg QE/g of total flavonoid and showed antioxidant activity. EAG showed in vitro and in vivo inhibitory activity against XO and significantly decreased serum uric acid level in PO-induced hyperuricemic rats without liver toxicity. These results show that EAG significantly attenuates hyperuricemia by inhibiting XO activity, which resulted in the decrease of serum uric acid level. Therefore, EAG might possess a potential therapeutic ability for improving gout.


Assuntos
Animais , Ratos , Etanol , Gota , Hiperuricemia , Hipoxantina , Técnicas In Vitro , Fígado , Potássio , Prevalência , Ácido Úrico , Xantina Oxidase
11.
Kidney Research and Clinical Practice ; : 207-208, 2017.
Artigo em Inglês | WPRIM | ID: wpr-218957

RESUMO

No abstract available.


Assuntos
Alopurinol , Febuxostat , Xantina Oxidase , Xantina
12.
Journal of Veterinary Science ; : 193-200, 2017.
Artigo em Inglês | WPRIM | ID: wpr-109779

RESUMO

To investigate the effects of molybdenum (Mo) and/or cadmium (Cd) on antioxidant function and the apoptosis-related genes in duck spleens. Sixty healthy 11-day-old ducks were randomly divided into six groups of 10 ducks (control, low Mo group, high Mo, Cd, low Mo + Cd, and high Mo + Cd groups). All were fed a basal diet containing low or high dietary doses of Mo and/or Cd. Relative spleen weight, antioxidant indices, apoptosis-related gene mRNA expression levels, and ultrastructural changes were evaluated after 120 days. The results showed that the relative spleen weight decreased significantly in the high Mo + Cd treatment group which compared with control group. Malondialdehyde levels increased and xanthine oxidase and catalase activities decreased in the Mo and/or Cd groups compared with levels in the control group. Bak-1 and Caspase-3 expressions were upregulated in the high Mo + Cd group, while Bcl-2 was downregulated. In addition, mitochondrial crest fracture, swelling, vacuolation, deformed nuclei, and karyopyknosis in both Mo + Cd treated groups were more severe than in the other groups. The results suggest that Mo and/or Cd can induce oxidative stress and apoptosis of spleen via effects on the mitochondrial intrinsic pathway. Moreover, the results indicate the two elements have a possible synergistic relationship.


Assuntos
Apoptose , Cádmio , Caspase 3 , Catalase , Dieta , Patos , Malondialdeído , Molibdênio , Estresse Oxidativo , RNA Mensageiro , Baço , Xantina Oxidase
13.
The Korean Journal of Physiology and Pharmacology ; : 371-376, 2017.
Artigo em Inglês | WPRIM | ID: wpr-727979

RESUMO

The caudal subnucleus of the spinal trigeminal nucleus (medullary dorsal horn; MDH) receives direct inputs from small diameter primary afferent fibers that predominantly transmit nociceptive information in the orofacial region. Recent studies indicate that reactive oxygen species (ROS) is involved in persistent pain, primarily through spinal mechanisms. In this study, we aimed to investigate the role of xanthine/xanthine oxidase (X/XO) system, a known generator of superoxide anion (O₂(·−)), on membrane excitability in the rat MDH neurons. For this, we used patch clamp recording and confocal imaging. An application of X/XO (300 µM/30 mU) induced membrane depolarization and inward currents. When slices were pretreated with ROS scavengers, such as phenyl N-tert-butylnitrone (PBN), superoxide dismutase (SOD), and catalase, X/XO-induced responses decreased. Fluorescence intensity in the DCF-DA and DHE-loaded MDH cells increased on the application of X/XO. An anion channel blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), significantly decreased X/XO-induced depolarization. X/XO elicited an inward current associated with a linear current-voltage relationship that reversed near −40 mV. X/XO-induced depolarization reduced in the presence of La³⁺, a nonselective cation channel (NSCC) blocker, and by lowering the external sodium concentration, indicating that membrane depolarization and inward current are induced by influx of Na⁺ ions. In conclusion, X/XO-induced ROS modulate the membrane excitability of MDH neurons, which was related to the activation of NSCC.


Assuntos
Animais , Ratos , Catalase , Dor Facial , Fluorescência , Íons , Membranas , Neurônios , Oxirredutases , Células do Corno Posterior , Espécies Reativas de Oxigênio , Sódio , Corno Dorsal da Medula Espinal , Superóxido Dismutase , Superóxidos , Núcleo Espinal do Trigêmeo , Xantina Oxidase
14.
Artigo em Inglês | AIM | ID: biblio-1260359

RESUMO

Increased uric acid levels are correlated with cardiovascular disease, particularly with ischaemic heart disease. Xanthine oxidase inhibitors, especially allopurinol, lower the risk of ischaemic heart disease due to their effects on reactive oxygen species and endothelial function. In chronic stable angina pectoris, allopurinol increases the median time to ST depression, time to chest pain, and total exercise time. On the other hand, it has been reported that allopurinol has a beneficial effect on ischaemic patients referred for angioplasty, but there are insufficient data regarding its effect on acute myocardial infarction patients. Moreover, other important actions of allopurinol are regression of left ventricular hypertrophy and improvement in the results of cardiac rehabilitation. The efficacy of allopurinol has recently been acknowledged by the European Society of Cardiology guidelines for stable angina pectoris, but the particular role of allopurinol in ischaemic heart disease patients is not fully established.


Assuntos
Alopurinol , Isquemia Miocárdica , África do Sul , Xantina Oxidase
15.
Braz. j. pharm. sci ; 52(4): 787-794, Oct.-Dec. 2016. tab, graf
Artigo em Inglês | LILACS | ID: biblio-951889

RESUMO

ABSTRACT Heroin is known to enhance catabolism and inhibit anabolism of purine nucleotides, leading to purine nucleotide deficiencies in rat brains. Here, we determined the effect of exogenous purine nucleotide administration on purine nucleotide metabolism in the brains of heroin-dependent rats. Heroin was administrated in increasing doses for 9 consecutive days to induce addiction, and the biochemical changes associated with heroin and purine nucleotide administration were compared among the treated groups. HPLC was performed to detect the absolute concentrations of purine nucleotides in the rat brain cortices. The enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the treated rat cortices were analyzed, and qRT-PCR was performed to determine the relative expression of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT), and adenosine kinase (AK). Heroin increased the enzymatic activity of ADA and XO, and up-regulated the transcription of ADA and XO. Alternatively, heroin decreased the transcription of AK, APRT, and HGPRT in the rat cortices. Furthermore, purine nucleotide administration alleviated the effect of heroin on purine nucleotide content, activity of essential purine nucleotide metabolic enzymes, and transcript levels of these genes. Our findings therefore represent a novel, putative approach to the treatment of heroin addiction.


Assuntos
Animais , Masculino , Ratos , Nucleosídeos de Purina/análise , Nucleotídeos de Purina/efeitos adversos , Heroína/efeitos adversos , Xantina Oxidase/análise , Adenosina Desaminase/análise , Dependência de Heroína/classificação
16.
International Journal of Oral Biology ; : 141-147, 2016.
Artigo em Coreano | WPRIM | ID: wpr-124488

RESUMO

Reactive oxygen species (ROS) and nitrogen species (RNS) are both important signaling molecules involved in pain transmission in the dorsal horn of the spinal cord. Xanthine oxidase (XO) is a well-known enzyme for the generation of superoxide anions (O₂˙⁻), while S-nitroso-N-acetyl-DL-penicillamine (SNAP) is a representative nitric oxide (NO) donor. In this study, we used patch clamp recording in spinal slices of rats to investigate the effects of O₂˙⁻ and NO on the excitability of substantia gelatinosa (SG) neurons. We also used confocal scanning laser microscopy to measure XO- and SNAP-induced ROS and RNS production in live slices. We observed that the ROS level increased during the perfusion of xanthine and xanthine oxidase (X/XO) compound and SNAP after the loading of 2',7'-dichlorofluorescin diacetate (H₂DCF-DA), which is an indicator of intracellular ROS and RNS. Application of ROS donors such as X/XO, β-nicotinamide adenine dinucleotide phosphate (NADPH), and 3-morpholinosydnomimine (SIN-1) induced a membrane depolarization and inward currents. SNAP, an RNS donor, also induced membrane depolarization and inward currents. X/XO-induced inward currents were significantly decreased by pretreatment with phenyl N-tert-butylnitrone (PBN; nonspecific ROS and RNS scavenger) and manganese(III) tetrakis(4-benzoic acid) porphyrin (MnTBAP; superoxide dismutase mimetics). Nitro-L-arginine methyl ester (NAME; NO scavenger) also slightly decreased X/XO-induced inward currents, suggesting that X/XO-induced responses can be involved in the generation of peroxynitrite (ONOO⁻). Our data suggest that elevated ROS, especially O₂˙⁻, NO and ONOO⁻, in the spinal cord can increase the excitability of the SG neurons related to pain transmission.


Assuntos
Animais , Humanos , Ratos , Adenina , Membranas , Microscopia Confocal , Neurônios , Óxido Nítrico , Nitrogênio , Perfusão , Ácido Peroxinitroso , Espécies Reativas de Oxigênio , Medula Espinal , Corno Dorsal da Medula Espinal , Substância Gelatinosa , Superóxido Dismutase , Superóxidos , Doadores de Tecidos , Xantina , Xantina Oxidase
17.
Pakistan Journal of Pharmaceutical Sciences. 2016; 29 (2): 429-432
em Inglês | IMEMR | ID: emr-176372

RESUMO

In the present research study 2-Aminoanthraquinone were scrutinized for their antimalarial and Xanthine oxidase inhibitor potential. It demonstrated marked concentration dependent antimalarial activity with maximum effect of 89.06% and with IC[50] of 34.17 micro M. Regarding Xanthine oxidase inhibitor activity, it evoked significant effect with 57.45% activity with IC[50] value of 81.57.19 micro M. In conclusion, 2-Aminoanthraquinone showed potent antimalarial and xanthine oxidase inhibitory activity


Assuntos
Antimaláricos , Xantina Oxidase/antagonistas & inibidores , Técnicas In Vitro
18.
China Journal of Chinese Materia Medica ; (24): 3818-3825, 2015.
Artigo em Chinês | WPRIM | ID: wpr-237725

RESUMO

Human xanthine oxidase is considered to be a target for therapy of hyperuricemia. Cichorium intybus is a Chinese plant medicine which widely used in Xinjiang against various diseases. In order to screen the inhibitors of xanthine oxidase from C. intybus and to explore main pharmacological actions of cichory a compound collection of C. intybus was built via consulting related references about chemical research on cichory. The three-dimensional crystal structure of xanthine oxidase (PDB code: 1N5X) from Protein Data Bank was downloaded.. Autodock 4.2 was employed to screen the inhibitors of xanthine oxidase from cichory 70 compounds were found to possess quite low binding free energy comparing with TEI (febuxostat). C. intybus contains constituents possessing potential inhibitive activity against xanthine oxidase. It can explain the main pharmacological actions of cichory which can significantly lower the level of serum uric acid.


Assuntos
Humanos , Cichorium intybus , Química , Bases de Dados de Proteínas , Medicamentos de Ervas Chinesas , Química , Inibidores Enzimáticos , Química , Simulação de Acoplamento Molecular , Estrutura Molecular , Xantina Oxidase , Metabolismo
19.
Acta Pharmaceutica Sinica ; (12): 447-452, 2015.
Artigo em Chinês | WPRIM | ID: wpr-251759

RESUMO

A double targets of high throughput screening model for xanthine oxidase inhibitors and superoxide anion scavengers was established. In the reaction system of xanthine oxidase, WST-1 works as the probe for the ultra oxygen anion generation, and product uric acid works as xanthine oxidase activity indicator. By using SpectraMax M5 continuous spectrum enzyme sign reflectoscope reflector, the changes of these indicators' concentration were observed and the influence factors of this reaction system to establish the high throughput screening model were studied. And the model is confirmed by positive drugs. In the reaction system, the final volume of reaction system is 50 μL and the concentrations of xanthine oxidase is 4 mU x mL(-1), xanthine 250 μmol x L(-1) and WST-1 100 μmol x L(-1), separately. The Z'-factor of model for xanthine oxidase inhibitors is 0.537 4, S/N is 47.519 9; the Z'-factor of model for superoxide anion scavengers is 0.507 4, S/N is 5.388 9. This model for xanthine oxidase inhibitors and superoxide anion scavengers has more common characteristics of the good stability, the fewer reagent types and quantity, the good repeatability, and so on. And it can be widely applied in high-throughput screening research.


Assuntos
Inibidores Enzimáticos , Farmacologia , Sequestradores de Radicais Livres , Farmacologia , Ensaios de Triagem em Larga Escala , Superóxidos , Ácido Úrico , Xantina , Xantina Oxidase
20.
Chinese journal of integrative medicine ; (12): 229-233, 2015.
Artigo em Inglês | WPRIM | ID: wpr-267198

RESUMO

<p><b>OBJECTIVE</b>To observe the protective effects of safflor Injection (SI) and extract of Ginkgo biloba (EGB) on lung ischemia-reperfusion injury (LIRI) and investigate its mechanism.</p><p><b>METHODS</b>In vivo rabbit model of LIRI was reconstructed. Forty rabbits were randomly and equally divided into four groups: sham-operation group (sham group), ischemia-reperfusion group (model group), ischemia-reperfusion plus SI group (safflor group) and ischemia-reperfusion plus EGB injection group (EGB group). Malondialdehyde (MDA) content, superoxide dismutase (SOD) and xanthine oxidase (XO) activity in serum were measured. The wet/dry weight ratio (W/D) of the lung tissue and activity of myeloperoxidase (MPO) were also tested. Ultrastructure change of the lung tissue was observed by the electron microscope. The expression of intercellular adhesion molecule-1 (ICAM-1) was measured by immunohistochemistry (IHC).</p><p><b>RESULTS</b>In the model group, MDA and XO increased and SOD decreased in serum compared with the sham group (P<0.01). The values of W/D, MPO and ICAM-1 of the model group were higher than those of the sham group (P<0.01), but those of the safflor group and EGB group were significantly lower than those of the model group (P<0.01). The IHC demonstrated that ICAM-1 expression in lung tissue of the model group was significantly higher than those of the safflor group (P<0.01). Compared with safflor group, in the EGB group MDA, XO, MPO decreased, SOD and ICAM-1 expression increased (P<0.05), but the change of W/D was not statistically significant (P>0.05).</p><p><b>CONCLUSIONS</b>SI and EGB may attenuate LIRI through antioxidation, inhibition of neutrophil aggregation and down-regulation of ICAM-1 expression. But EGB had more effect on the antioxidation, while SI did better on regulating ICAM-1 expression.</p>


Assuntos
Animais , Feminino , Masculino , Coelhos , Ginkgo biloba , Química , Imuno-Histoquímica , Injeções , Molécula 1 de Adesão Intercelular , Metabolismo , Pulmão , Patologia , Malondialdeído , Metabolismo , Extratos Vegetais , Farmacologia , Usos Terapêuticos , Substâncias Protetoras , Farmacologia , Usos Terapêuticos , Traumatismo por Reperfusão , Sangue , Tratamento Farmacológico , Óleo de Cártamo , Farmacologia , Usos Terapêuticos , Superóxido Dismutase , Sangue , Xantina Oxidase , Sangue
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