Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.097
Filtrar
1.
Eur J Med Chem ; 271: 116443, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691887

RESUMO

Xanthine oxidase (XO) is a key enzyme for the production of uric acid in the human body. XO inhibitors (XOIs) are clinically used for the treatment of hyperuricemia and gout, as they can effectively inhibit the production of uric acid. Previous studies indicated that both indole and isoxazole derivatives have good inhibitory effects against XO. Here, we designed and synthesized a novel series of N-5-(1H-indol-5-yl)isoxazole-3-carboxylic acids according to bioisosteric replacement and hybridization strategies. Among the obtained target compounds, compound 6c showed the best inhibitory activity against XO with an IC50 value of 0.13 µM, which was 22-fold higher than that of the classical antigout drug allopurinol (IC50 = 2.93 µM). Structure-activity relationship analysis indicated that the hydrophobic group on the nitrogen atom of the indole ring is essential for the inhibitory potencies of target compounds against XO. Enzyme kinetic studies proved that compound 6c acted as a mixed-type XOI. Molecular docking studies showed that the target compound 6c could not only retain the key interactions similar to febuxostat at the XO binding site but also generate some new interactions, such as two hydrogen bonds between the oxygen atom of the isoxazole ring and the amino acid residues Ser876 and Thr1010. These results indicated that 5-(1H-indol-5-yl)isoxazole-3-carboxylic acid might be an efficacious scaffold for designing novel XOIs and compound 6c has the potential to be used as a lead for further the development of novel anti-gout candidates.


Assuntos
Ácidos Carboxílicos , Desenho de Fármacos , Inibidores Enzimáticos , Isoxazóis , Xantina Oxidase , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Relação Estrutura-Atividade , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Isoxazóis/química , Isoxazóis/farmacologia , Isoxazóis/síntese química , Ácidos Carboxílicos/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/síntese química , Estrutura Molecular , Humanos , Simulação de Acoplamento Molecular , Indóis/farmacologia , Indóis/química , Indóis/síntese química , Relação Dose-Resposta a Droga
2.
Front Immunol ; 15: 1362642, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38745649

RESUMO

Hyperuricaemia (HUA) is a metabolic disorder characterised by high blood uric acid (UA) levels; moreover, HUA severity is closely related to the gut microbiota. HUA is also a risk factor for renal damage, diabetes, hypertension, and dyslipidaemia; however, current treatments are associated with detrimental side effects. Alternatively, Fangyukangsuan granules are a natural product with UA-reducing properties. To examine their efficacy in HUA, the binding of small molecules in Fangyukangsuan granules to xanthine oxidase (XOD), a key factor in UA metabolism, was investigated via molecular simulation, and the effects of oral Fangyukangsuan granule administration on serum biochemical indices and intestinal microorganisms in HUA-model rats were examined. Overall, 24 small molecules in Fangyukangsuan granules could bind to XOD. Serum UA, creatinine, blood urea nitrogen, and XOD levels were decreased in rats treated with Fangyukangsuan granules compared to those in untreated HUA-model rats. Moreover, Fangyukangsuan granules restored the intestinal microbial structure in HUA-model rats. Functional analysis of the gut microbiota revealed decreased amino acid biosynthesis and increased fermentation of pyruvate into short-chain fatty acids in Fangyukangsuan granule-treated rats. Together, these findings demonstrate that Fangyukangsuan granules have anti-hyperuricaemic and regulatory effects on the gut microbiota and may be a therapeutic candidate for HUA.


Assuntos
Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Hiperuricemia , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Masculino , Ácido Úrico/sangue , Xantina Oxidase/metabolismo , Ratos Sprague-Dawley
3.
Ann Med ; 56(1): 2352022, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38753584

RESUMO

Uric acid (UA) levels in blood serum have been associated with hypertension, indicating a potential causal relationship between high serum UA levels and the progression of hypertension. Therefore, the reduction of serum UA level is considered a potential strategy for lowering and mitigating blood pressure. If an individual is at risk of developing or already manifesting elevated blood pressure, this intervention could be an integral part of a comprehensive treatment plan. By addressing hyperuricaemia, practitioners may subsidize the optimization of blood pressure regulation, which illustrates the importance of addressing UA levels as a valuable strategy within the broader context of hypertension management. In this analysis, we outlined the operational principles of effective xanthine oxidase inhibitors for the treatment of hyperuricaemia and hypertension, along with an exploration of the contribution of nanotechnology to this field.


Assuntos
Hipertensão , Hiperuricemia , Ácido Úrico , Xantina Oxidase , Humanos , Hiperuricemia/tratamento farmacológico , Hipertensão/tratamento farmacológico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Pressão Sanguínea/efeitos dos fármacos , Nanotecnologia/métodos , Anti-Hipertensivos/uso terapêutico
4.
Chem Biol Interact ; 396: 111034, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38723799

RESUMO

This study aimed to explore the antioxidant and prooxidative activity of two natural furanocoumarin derivatives, Bergaptol (4-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, BER) and Xanthotoxol (9-Hydroxy-7H-furo [3,2-g] [1]benzopyran-7-one, XAN). The collected thermodynamic and kinetic data demonstrate that both compounds possess substantial antiradical activity against HO• and CCl3OO• radicals in physiological conditions. BER exhibited better antiradical activity in comparison to XAN, which can be attributed to the enhanced deprotonation caused by the positioning of the -OH group on the psoralen ring. In contrast to highly reactive radical species, newly formed radical species BER• and XAN• exhibited negligible reactivity towards the chosen constitutive elements of macromolecules (fatty acids, amino acids, nucleobases). Furthermore, in the presence of O2•─, the ability to regenerate newly formed radicals BER• and XAN• was observed. Conversely, in physiological conditions in the presence of Cu(II) ions, both compounds exhibit prooxidative activity. Nevertheless, the prooxidative activity of both compounds is less prominent than their antioxidant activity. Furthermore, it has been demonstrated that anionic species can engage in the creation of a chelate complex, which restricts the reduction of metal ions when reducing agents are present (O2•─ and Asc─). Moreover, studies have demonstrated that these chelating complexes can be coupled with other radical species, hence enhancing their ability to inactivate radicals. Both compounds exhibited substantial inhibitory effects against enzymes involved in the direct or indirect generation of ROS: Xanthine Oxidase (XOD), Lipoxygenase (LOX), Myeloperoxidase (MPO), NADPH oxidase (NOX).


Assuntos
Antioxidantes , Furocumarinas , Furocumarinas/química , Furocumarinas/farmacologia , Cinética , Antioxidantes/química , Antioxidantes/farmacologia , Teoria da Densidade Funcional , Oxirredução , Termodinâmica , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lipoxigenase/metabolismo , Xantina Oxidase/metabolismo , Xantina Oxidase/antagonistas & inibidores , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia
5.
J Agric Food Chem ; 72(21): 12083-12099, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38757561

RESUMO

The development of food-derived antihyperuricemic substances is important for alleviating hyperuricemia (HUA) and associated inflammation. Here, novel peptides fromThunnus albacares (TAP) with strong antihyperuricemic activity were prepared. TAP was prepared by alkaline protease (molecular weight <1000 Da), with an IC50 value of xanthine oxidase inhibitory activity of 2.498 mg/mL, and 5 mg/mL TAP could reduce uric acid (UA) by 33.62% in human kidney-2 (HK-2) cells (P < 0.01). Mice were fed a high-purine diet and injected with potassium oxonate to induce HUA. Oral administration of TAP (600 mg/kg/d) reduced serum UA significantly by 42.22% and increased urine UA by 79.02% (P < 0.01) via regulating urate transporters GLUT9, organic anion transporter 1, and ATP-binding cassette subfamily G2. Meantime, TAP exhibited hepatoprotective and nephroprotective effects, according to histological analysis. Besides, HUA mice treated with TAP showed anti-inflammatory activity by decreasing the levels of toll-like receptor 4, nuclear factors-κB p65, NLRP3, ASC, and Caspase-1 in the kidneys (P < 0.01). According to serum non-targeted metabolomics, 91 differential metabolites between the MC and TAP groups were identified, and purine metabolism was considered to be the main pathway for TAP alleviating HUA. In a word, TAP exhibited strong antihyperuricemic activity both in vitro and in vivo.


Assuntos
Hiperuricemia , Peptídeos , Atum , Ácido Úrico , Animais , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Camundongos , Humanos , Ácido Úrico/metabolismo , Ácido Úrico/sangue , Peptídeos/administração & dosagem , Peptídeos/química , Peptídeos/farmacologia , Masculino , Proteínas de Peixes/química , Xantina Oxidase/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/genética , Linhagem Celular , Rim/efeitos dos fármacos , Rim/metabolismo
6.
J Pharm Biomed Anal ; 246: 116164, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38776585

RESUMO

Evaluating the quality of herbal medicine based on the content and activity of its main components is highly beneficial. Developing an eco-friendly determination method has significant application potential. In this study, we propose a new method to simultaneously predict the total flavonoid content (TFC), xanthine oxidase inhibitory (XO) activity, and antioxidant activity (AA) of Prunus mume using near-infrared spectroscopy (NIR). Using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetric method, uric acid colorimetric method, and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) free radical scavenging activity as reference methods, we analyzed TFC, XO, and AA in 90 P. mume samples collected from different locations in China. The solid samples were subjected to NIR. By employing spectral preprocessing and optimizing spectral bands, we established a rapid prediction model for TFC, XO, and AA using partial least squares regression (PLS). To improve the model's performance and eliminate irrelevant variables, competitive adaptive reweighted sampling (CARS) was used to calculate the pretreated full spectrum. Evaluation model indicators included the root mean square error of cross-validation (RMSECV) and determination coefficient (R2) values. The TFC, XO, and AA model, combining optimal spectral preprocessing and spectral bands, had RMSECV values of 0.139, 0.117, and 0.121, with RCV2 values exceeding 0.92. The root mean square error of prediction (RMSEP) for the TFC, XO, and AA model on the prediction set was 0.301, 0.213, and 0.149, with determination coefficient (RP2) values of 0.915, 0.933, and 0.926. The results showed a strong correlation between NIR with TFC, XO, and AA in P. mume. Therefore, the established model was effective, suitable for the rapid quantification of TFC, XO, and AA. The prediction method is simple and rapid, and can be extended to the study of medicinal plant content and activity.


Assuntos
Antioxidantes , Flavonoides , Prunus , Espectroscopia de Luz Próxima ao Infravermelho , Xantina Oxidase , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Flavonoides/análise , Prunus/química , Xantina Oxidase/antagonistas & inibidores , Antioxidantes/análise , Análise dos Mínimos Quadrados , Inibidores Enzimáticos/análise , Inibidores Enzimáticos/farmacologia , China
7.
Mol Med Rep ; 30(2)2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38818832

RESUMO

The present review expounds the advancements in the application and mechanisms of flavonoids in gouty arthritis, highlighting their significance in managing the disease. Gouty arthritis is among the most common and severe inflammatory diseases, caused by hyperuricemia and the deposition of sodium urate crystals in the joints and surrounding tissues, posing a serious threat to human life and health. Flavonoids, extracted from various herbs, have attracted significant attention due to their efficacy in improving gouty arthritis. The present study systematically reviews the in vivo studies and in vitro animal studies on flavonoids from herbal medicines for the treatment of gouty arthritis that have been previously published in the PubMed, ScienceDirect, Google Scholar and China National Knowledge Infrastructure databases between 2000 and 2023. The review of the literature indicated that flavonoids can improve gouty arthritis through multiple mechanisms. These include lowering xanthine oxidase activity, inhibiting uric acid (UA) synthesis, regulating UA transporters to promote UA excretion, reducing the inflammatory response and improving oxidative stress. These mechanisms predominantly involve regulating the NOD­like receptor 3 inflammasome, the Toll­like receptor 4/myeloid differentiation factor 88/nuclear factor­κB signaling pathway, and the levels of UA transporter proteins, namely recombinant urate transporter 1, glucose transporter 9, organic anion transporter (OAT)1 and OAT3. Various flavonoids used in traditional Chinese medicine hold therapeutic promise for gouty arthritis and are anticipated to pave the way for novel pharmaceuticals and clinical applications.


Assuntos
Artrite Gotosa , Flavonoides , Ácido Úrico , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/metabolismo , Humanos , Flavonoides/uso terapêutico , Flavonoides/farmacologia , Flavonoides/química , Animais , Ácido Úrico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Xantina Oxidase/metabolismo , Xantina Oxidase/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo
8.
J Ethnopharmacol ; 332: 118362, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38768838

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In ancient times, ginseng was used for hyperuricemia treatment as described in the classic traditional Chinese medical text Shang Han Lun. Recent studies have shown that common ginsenosides and rare ginsenosides (RGS) are the main active compounds in ginseng. RGS have higher activity and are less studied in the treatment of hyperuricemia. AIM OF THE STUDY: To determine whether RGS prevents and ameliorates potassium oxonate(PO)-induced hyperuricemia and concomitant spermatozoa damage in mice and the possible underlying mechanisms. MATERIALS AND METHODS: Potassium oxonate (PO, 300 mg/kg) induced hyperuricemia in mice via the oral administration of RGS (50, 100, or 200 mg/kg) or allopurinol (ALL, 5 mg/kg) for 35 days. Uric acid (UA) and xanthine oxidase (XO) levels were measured to assess the degree of histopathological damage in the liver, kidney, and testis, and renal creatinine (CRE), urea nitrogen (BUN), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and inflammatory factor (IL-1ß) levels were measured to calculate the sperm density. Mechanisms were also explored based on blood and urine metabolomics and the gut microbiota. RESULTS: In this study, we demonstrated that RGS containing Rg3, Rk1, Rg6, and Rg5 could reduce serum UA levels, inhibit serum and hepatic XO activity, reduce renal CRE and BUN levels, further restore renal SOD and GSH activities, reduce the accumulation of MDA in the kidneys, and attenuate the production of renal IL-1ß. RGS was able to restore sperm density. Metabolomic analysis revealed that RGS improved sphingolipid metabolism, pyrimidine metabolism, and other metabolic pathways. 16S rDNA sequencing revealed that RGS could increase gut microbial diversity, restore the Firmicutes/Bacteroidetes (F/B) ratio, and adjust the intestinal microbial balance. Spearman's correlation analysis revealed a correlation between differentially metabolites and the gut microbiota. Lactobacillus and Akkermansia are the core genera. CONCLUSION: RGS can be a candidate for the prevention and amelioration of hyperuricemia and concomitant sperm damage. Its mechanism of action is closely related to sphingolipid metabolism, pyrimidine metabolism, and the modulation of gut microbiota, such as Lactobacillus and Akkermansia.


Assuntos
Microbioma Gastrointestinal , Ginsenosídeos , Hiperuricemia , Metabolômica , Espermatozoides , Animais , Masculino , Hiperuricemia/tratamento farmacológico , Ginsenosídeos/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Camundongos , Ácido Oxônico , Xantina Oxidase/metabolismo , Ácido Úrico/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia
9.
Eur Rev Med Pharmacol Sci ; 28(7): 2817-2826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639521

RESUMO

OBJECTIVE: Testicular ischemia-reperfusion induced by testicular torsion-detorsion increases the level of reactive oxygen species, leading to testicular damage. Allicin, one of the most active ingredients in garlic, is a significant exogenous antioxidant. In the research, the efficacy of allicin in treating testicular ischemia-reperfusion injury was assessed. MATERIALS AND METHODS: The study included sixty Sprague-Dawley male rats. Three groups with 20 rats per group were created as follows: control group, testicular ischemia/reperfusion-induced group, and testicular ischemia-reperfusion plus treatment with allicin group. The control group underwent a sham operation of the left testis without other interventions. In the testicular ischemia/reperfusion-induced group, rat left testis was subjected to 720° torsion for two hours and then detorsion. In the allicin-treated group, in addition to testicular ischemia-reperfusion, 50 mg/kg of allicin was injected intraperitoneally, starting immediately following detorsion. Testicular tissue samples were obtained to measure the protein expression of xanthine oxidase, which is a major source of reactive oxygen species formation, malondialdehyde level (a reliable marker of reactive oxygen species), and testicular spermatogenic function. RESULTS: Testicular ischemia-reperfusion significantly increased the expression of xanthine oxidase and malondialdehyde levels in ipsilateral testes while reducing testicular spermatogenic function. The expression of xanthine oxidase and malondialdehyde levels were significantly lower in ipsilateral testes, whereas testicular spermatogenic function in the allicin-treated group was significantly higher compared with those in the testicular ischemia-reperfusion group. CONCLUSIONS: Our findings indicate that allicin administration improves ischemia/reperfusion-induced testicular damage by limiting reactive oxygen species generation via inhibition of xanthine oxidase expression.


Assuntos
Dissulfetos , Traumatismo por Reperfusão , Torção do Cordão Espermático , Ácidos Sulfínicos , Ratos , Masculino , Animais , Humanos , Torção do Cordão Espermático/tratamento farmacológico , Torção do Cordão Espermático/complicações , Torção do Cordão Espermático/metabolismo , Ratos Sprague-Dawley , Xantina Oxidase/metabolismo , Xantina Oxidase/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Testículo , Traumatismo por Reperfusão/metabolismo , Antioxidantes/farmacologia , Isquemia/metabolismo , Malondialdeído/metabolismo
10.
Biomolecules ; 14(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38672506

RESUMO

Parkinson's disease (PD) is a neurodegenerative movement disorder associated with a loss of dopamine neurons in the substantia nigra. The diagnosis of PD is sensitive since it shows clinical features that are common with other neurodegenerative diseases. In addition, most symptoms arise at the late stage of the disease, where most dopaminergic neurons are already damaged. Several studies reported that oxidative stress is a key modulator in the development of PD. This condition occurs due to excess reactive oxygen species (ROS) production in the cellular system and the incapability of antioxidants to neutralize it. In this study, we focused on the pathology of PD by measuring serum xanthine oxidase (XO) activity, which is an enzyme that generates ROS. Interestingly, the serum XO activity of patients with PD was markedly upregulated compared to patients with other neurological diseases (ONDs) as a control. Moreover, serum XO activity in patients with PD showed a significant correlation with the disease severity based on the Hoehn and Yahr (HY) stages. The investigation of antioxidant status also revealed that serum uric acid levels were significantly lower in the severe group (HY ≥ 3) than in the ONDs group. Together, these results suggest that XO activity may contribute to the development of PD and might potentially be a biomarker for determining disease severity in patients with PD.


Assuntos
Antioxidantes , Doença de Parkinson , Ácido Úrico , Xantina Oxidase , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/metabolismo , Xantina Oxidase/sangue , Xantina Oxidase/metabolismo , Masculino , Feminino , Idoso , Antioxidantes/metabolismo , Pessoa de Meia-Idade , Ácido Úrico/sangue , Biomarcadores/sangue , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Espécies Reativas de Oxigênio/sangue
11.
J Asian Nat Prod Res ; 26(5): 555-561, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38563409

RESUMO

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).


Assuntos
Pironas , Talaromyces , Xantina Oxidase , Talaromyces/química , Estrutura Molecular , Pironas/química , Pironas/farmacologia , Pironas/isolamento & purificação , Xantina Oxidase/antagonistas & inibidores , Ressonância Magnética Nuclear Biomolecular , Naftalenos/química , Naftalenos/isolamento & purificação , Naftalenos/farmacologia , Dicroísmo Circular
12.
Talanta ; 274: 126007, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38583331

RESUMO

Hypoxanthine (Hx), produced by adenosine triphosphate (ATP) metabolism, is a valuable indicator that determines the quality and degradation status of meat products and is also an important biochemical marker to certain diseases such as gout. The rapid emergence of paper-based enzyme biosensors has already revolutionized its on-site determination. But it is still limited by the complex patterning and fabrication, unstable enzyme and uneven coloration. This work aims to develop an eco-friendly method to construct engineered paper microfluidic, which seeks to produce reaction and non-reaction zones without any patterning procedure. Chito-oligosaccharide (COS), derived from shrimp shells, was used to modify nitrocellulose membranes and immobilize xanthine oxidase (XOD) and chromogenic agent of nitro blue tetrazolium chloride (NBT). After modification, micro fluids could converge into the modification area and Hx could be detected by XOD-catalyzed conversion. Due to the positively charged cationic basic properties of COS, the enzyme storage stability and the color homogeneity could be greatly strengthened through the electrostatic attraction between COS and XOD and formazan product. The detection limit (LOD) is 2.30 µM; the linear range is 0.05-0.35 mM; the complete test time can be as short as 5 min. The COS-based biosensor shows high specificity and can be used directly for Hx in complex samples such as fish and shrimp samples, and different broths. This biosensor is eco-friendly, nontechnical, economical and therefore a compelling platform for on-site or home-based detection of food freshness.


Assuntos
Técnicas Biossensoriais , Colódio , Hipoxantina , Oligossacarídeos , Xantina Oxidase , Animais , Oligossacarídeos/química , Oligossacarídeos/análise , Técnicas Biossensoriais/métodos , Hipoxantina/análise , Hipoxantina/química , Colódio/química , Xantina Oxidase/química , Xantina Oxidase/metabolismo , Peixes , Quitina/química , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Química Verde/métodos , Propriedades de Superfície , Limite de Detecção
13.
Food Chem ; 450: 139242, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38631208

RESUMO

The development of facile, low-cost reliable, and precise onsite assays for the bioactive component hypoxanthine (Hx) in meat products is significant for safeguarding food safety and public health. Herein, we proposed a smartphone-assissted aggregation-induced emission (AIE) fluorogen tetraphenylethene (TPE)-incorporated amorphous Fe-doped phosphotungstates (Fe-Phos@TPE) nanozyme-based ratiometric fluorescence-colorimetric dual-mode biosensor for achieving the onsite visual detection of Hx. When the Hx existed, xanthine oxidase (XOD) catalyzed Hx into H2O2 to be further catalyzed into •OH by the prominent peroxidase activity of Fe-Phos@TPE at pH = 6.5, resulting in the oxidization of nonfluorescent o-phenylenediamine (OPD, naked-eye colorless) to be yellow fluorescent emissive 2,3-diaminophenazine (DAP, naked-eye dark yellow) at 550 nm as well as the intrinsic blue fluorescence of Fe-Phos@TPE at 440 nm to be decreased via inner-filter effect (IFE) action, thereby realizing a multi-enzyme cascade catalytic reaction at near-neutral pH to overcome the traditional acidity dependence-induced time-consuming and low sensitivity troublesome.


Assuntos
Técnicas Biossensoriais , Hipoxantina , Produtos da Carne , Técnicas Biossensoriais/instrumentação , Hipoxantina/análise , Hipoxantina/química , Produtos da Carne/análise , Xantina Oxidase/química , Xantina Oxidase/metabolismo , Contaminação de Alimentos/análise , Animais , Corantes Fluorescentes/química , Fluorescência , Smartphone , Colorimetria/métodos
14.
Food Chem ; 451: 139453, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38677136

RESUMO

Establishing a rapid and accurate method for monitoring the freshness of aquatic products is of great importance. Hypoxanthine has been considered an essential indicator of aquatic products' freshness. Here, a novel smartphone colorimetric / inductively coupled plasma mass spectrometry (ICP-MS) / photothermal three-mode sensing strategy was established for monitoring hypoxanthine. Hypoxanthine can be catalyzed by xanthine oxidase to H2O2 and uric acid, which can simultaneously degrade MnO2 nanosheets (NSs) to Mn2+. After filter-assisted separation, the smartphone and ICP-MS were performed by monitoring the color of the membrane and the Mn2+ in the filtrate. Additionally, MnO2 NSs can facilitate the oxidation of dopamine to form polydopamine nanoparticles, which exhibit strong photothermal efficiency. The approach successfully monitored the deterioration of aquatic products under various storage conditions through portable thermometers and smartphones with low limits of detection (LODs), providing a potential application for in-situ evaluation of the freshness of aquatic products.


Assuntos
Técnicas Biossensoriais , Hipoxantina , Óxidos , Hipoxantina/análise , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Óxidos/química , Animais , Compostos de Manganês/química , Armazenamento de Alimentos , Contaminação de Alimentos/análise , Alimentos Marinhos/análise , Limite de Detecção , Colorimetria/métodos , Colorimetria/instrumentação , Espectrometria de Massas , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Peixes , Xantina Oxidase/química , Xantina Oxidase/metabolismo , Smartphone , Indóis , Polímeros
15.
Food Chem ; 451: 139444, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38678657

RESUMO

Hyperuricemia (HU) is a metabolic disorder caused by the overproduction or underexcretion of uric acid (UA) in the human body. Several approved drugs for the treatment of HU are available in the market; however, all these allopathic drugs exhibit multiple side effects. Therefore, the development of safe and effective anti-HU drugs is an urgent need. Natural compounds derived from foods and plants have the potential to decrease UA levels. Recently, food-derived bioactive peptides (FBPs) have gained attention as a functional ingredient owing to their biological activities. In the current review, we aim to explore the urate-lowering potential and the underlying mechanisms of FBPs. We found that FBPs mitigate HU by reducing blood UA levels through inhibiting key enzymes such as xanthine oxidase, increasing renal UA excretion, inhibiting renal UA reabsorption, increasing anti-oxidant activities, regulating inflammatory mediators, and addressing gut microbiota dysbiosis. In conclusion, FBPs exhibit strong potential to ameliorate HU.


Assuntos
Hiperuricemia , Peptídeos , Ácido Úrico , Humanos , Peptídeos/farmacologia , Peptídeos/química , Peptídeos/administração & dosagem , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Animais , Ácido Úrico/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Antioxidantes/química , Antioxidantes/farmacologia , Xantina Oxidase/metabolismo , Peptídeos Bioativos de Alimentos
16.
Eur J Pharm Sci ; 198: 106778, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38653341

RESUMO

Uric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 µM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50 % of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments.


Assuntos
Benzaldeídos , Gota , Hiperuricemia , Semicarbazidas , Xantina Oxidase , Animais , Hiperuricemia/tratamento farmacológico , Masculino , Semicarbazidas/farmacologia , Semicarbazidas/uso terapêutico , Semicarbazidas/química , Camundongos , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Benzaldeídos/química , Gota/tratamento farmacológico , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Ácido Úrico/sangue , Humanos
17.
Am J Physiol Renal Physiol ; 326(6): F1004-F1015, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38634129

RESUMO

Humans are predisposed to gout because they lack uricase that converts uric acid to allantoin. Rodents have uricase, resulting in low basal serum uric acid. A uricase inhibitor raises serum uric acid in rodents. There were two aims of the study in polycystic kidney disease (PKD): 1) to determine whether increasing serum uric acid with the uricase inhibitor, oxonic acid, resulted in faster cyst growth and 2) to determine whether treatment with the xanthine oxidase inhibitor, oxypurinol, reduced the cyst growth caused by oxonic acid. Orthologous models of human PKD were used: PCK rats, a polycystic kidney and hepatic disease 1 (Pkhd1) gene model of autosomal recessive PKD (ARPKD) and Pkd1RC/RC mice, a hypomorphic Pkd1 gene model. In PCK rats and Pkd1RC/RC mice, oxonic acid resulted in a significant increase in serum uric acid, kidney weight, and cyst index. Mechanisms of increased cyst growth that were investigated were proinflammatory cytokines, the inflammasome, and crystal deposition in the kidney. Oxonic acid resulted in an increase in proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice. Oxonic acid did not cause activation of the inflammasome or uric acid crystal deposition in the kidney. In Pkd1RC/RC male and female mice analyzed together, oxypurinol decreased the oxonic acid-induced increase in cyst index. In summary, increasing serum uric acid by inhibiting uricase with oxonic acid results in an increase in kidney weight and cyst index in PCK rats and Pkd1RC/RC mice. The effect is independent of inflammasome activation or crystal deposition in the kidney.NEW & NOTEWORTHY This is the first reported study of uric acid measurements and xanthine oxidase inhibition in polycystic kidney disease (PKD) rodents. Raising serum uric acid with a uricase inhibitor resulted in increased kidney weight and cyst index in Pkd1RC/RC mice and PCK rats, elevated levels of proinflammatory cytokines in the serum and kidney in Pkd1RC/RC mice, and no uric acid crystal deposition or activation of the caspase-1 inflammasome in the kidney.


Assuntos
Modelos Animais de Doenças , Rim , Doenças Renais Policísticas , Urato Oxidase , Ácido Úrico , Animais , Ácido Úrico/sangue , Doenças Renais Policísticas/patologia , Doenças Renais Policísticas/metabolismo , Doenças Renais Policísticas/tratamento farmacológico , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Oxipurinol/farmacologia , Ácido Oxônico/farmacologia , Inibidores Enzimáticos/farmacologia , Ratos , Feminino , Inflamassomos/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Camundongos , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo , Ratos Sprague-Dawley , Camundongos Endogâmicos C57BL
18.
Int J Mol Sci ; 25(5)2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38474193

RESUMO

Upregulation of free radical-generating NADPH oxidases (NOX), xanthine oxidoreductase (XOR), and neutrophil infiltration-induced, NOX2-mediated respiratory burst contribute to renal ischemia-reperfusion injury (IRI), but their roles may depend on the severity of IRI. We investigated the role of NOX, XOR, and neutrophils in developing IRI of various severities. C57BL/6 and Mcl-1ΔMyelo neutrophil-deficient mice were used. Oxidases were silenced by RNA interference (RNAi) or pharmacologically inhibited. Kidney function, morphology, immunohistochemistry and mRNA expression were assessed. After reperfusion, the expression of NOX enzymes and XOR increased until 6 h and from 15 h, respectively, while neutrophil infiltration was prominent from 3 h. NOX4 and XOR silencing or pharmacological XOR inhibition did not protect the kidney from IRI. Attenuation of NOX enzyme-induced oxidative stress by apocynin and neutrophil deficiency improved kidney function and ameliorated morphological damage after mild but not moderate/severe IRI. The IR-induced postischemic renal functional impairment (BUN, Lcn-2), tubular necrosis score, inflammation (TNF-α, F4/80), and decreases in the antioxidant enzyme (GPx3) mRNA expression were attenuated by both apocynin and neutrophil deficiency. Inhibition of NOX enzyme-induced oxidative stress or the lack of infiltration by NOX2-expressing neutrophils can attenuate reperfusion injury after mild but not moderate/severe renal IR.


Assuntos
Acetofenonas , Injúria Renal Aguda , Traumatismo por Reperfusão , Camundongos , Animais , NADPH Oxidases/metabolismo , Neutrófilos/metabolismo , Camundongos Endogâmicos C57BL , Rim/metabolismo , Traumatismo por Reperfusão/genética , Xantina Desidrogenase/metabolismo , RNA Mensageiro
19.
Fitoterapia ; 175: 105926, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38537887

RESUMO

Hyperuricemia (HUA) is a metabolic disease characterized by the increase of serum uric acid (UA) level. Sargentodoxae Caulis (SC) is a commonly used herbal medicine for the treatment of gouty arthritis, traumatic swelling, and rheumatic arthritis in clinic. In this study, a total of fifteen compounds were identified in SC water extract using UHPLC-Q-TOF-MS/MS, including three phenolic acids, seven phenolic glycosides, four organic acids, and one lignan. Then, to study the hypouricemia effect of SC, a HUA mouse model was induced using a combination of PO, HX, and 20% yeast feed. After 14 days of treatment with the SC water extract, the levels of serum UA, creatinine (CRE), blood urea nitrogen (BUN) were reduced significantly, and the organ indexes were restored, the xanthine oxidase (XOD) activity were inhibited as well. Meanwhile, SC water extract could ameliorate the pathological status of kidneys and intestine of HUA mice. Additionally, quantitative real-time PCR (qRT-PCR) and western blotting results showed that SC water extract could increase the expression of ATP binding cassette subfamily G member 2 (ABCG2), organic cation transporter 1 (OCT1), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3), whereas decrease the expression of glucose transporter 9 (GLUT9). This study provided a data support for the clinical application of SC in the treatment of HUA.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Hiperuricemia , Ácido Úrico , Xantina Oxidase , Animais , Camundongos , Hiperuricemia/tratamento farmacológico , Masculino , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácido Úrico/sangue , Xantina Oxidase/metabolismo , Modelos Animais de Doenças , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Rim/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Transportadores de Ânions Orgânicos/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia
20.
Inflammopharmacology ; 32(3): 1929-1940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38556563

RESUMO

Gout is a metabolic condition characterized by the accumulation of urate crystals in the synovial joints. These crystal depositions result in joint swelling and increased concentration of serum uric acid in blood. The commercially available drugs lower serum uric acid levels and reduce inflammation, but these standard therapies have many side effects. This study aimed to investigate anti-gout and anti-inflammatory properties of curcumin nanoparticles (CNPs). For this purpose, CNPs were prepared by dissolving curcumin into dichloromethane. Then, gout was induced by injecting monosodium urate crystals (MSU) in the ankle joint and in the intra-peritoneal cavity which caused ankle swelling and increased blood uric acid levels. CNPs in different concentrations (5, 10, and 20 ppm) and allopurinol were orally administered. The MSU crystals increased the xanthine oxidase levels both in serum and the liver. Moreover, MSU crystals increased the serum levels of interleukin 1ß, interleukin-6, tumor necrosis factor-alpha, liver function tests markers, renal function tests markers, and lipid profiles. However, the administration of CNPs decreased the levels of all these variables. CNPs increased the serum high-density lipoprotein and interleukin-10 levels. Moreover, CNPs also reduced ankle swelling significantly. Hence, the levels of xanthine oxidase, uric acid and ankle swelling were reduced significantly by oral administration of CNPs. Our findings indicate that CNPs through their anti-inflammatory properties significantly alleviate gouty arthritis. Thus, the study concluded that CNPs can be developed as an efficient anti-gout agent with minimal side effects.


Assuntos
Anti-Inflamatórios , Artrite Gotosa , Curcumina , Camundongos Endogâmicos BALB C , Nanopartículas , Ácido Úrico , Animais , Curcumina/farmacologia , Curcumina/administração & dosagem , Ácido Úrico/sangue , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/induzido quimicamente , Camundongos , Nanopartículas/administração & dosagem , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/administração & dosagem , Masculino , Xantina Oxidase/metabolismo , Supressores da Gota/farmacologia , Supressores da Gota/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...