Xanthine Oxidase Research Articles

Untargeted metabolomics reveals the regulatory effect of geniposidic acid on lipid accumulation in HepG2 cells and Caenorhabditis elegans and validation in hyperlipidemic hamsters

BackgroundGeniposidic acid (GPA) alleviates oxidative stress and inflammation in mice However, whether it can effectively regulate lipid accumulation and prevent hyperlipidemia requires further investigation. PurposeThis study combined the untargeted metabolomics of cells and a Caenorhabditis elegans model to evaluate the anti-hyperlipidemic potential of GPA by modulating oxidative stress and regulating lipid metabolism. A golden hamster model of hyperlipidemia was used to further validate the lipid-lowering effect and mechanism of action of GPA. MethodsChemical staining, immunofluorescence, and flow cytometry were performed to examine the effects of GPA on lipid accumulation and oxidative stress. Untargeted metabolomic analysis of cells and C. elegans was performed using ultra-performance liquid chromatography coupled with quadrupole electrostatic field Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap MS) to identify biomarkers altered by GPA action, analyze the affected metabolic pathways, and validate the mechanisms by which GPA regulates lipid metabolism and oxidative stress. A golden hamster model of hyperlipidemia was established to test the lipid-lowering effects of GPA. Body weight, biochemical markers, rate-limiting enzymes, and key proteins were assessed. Hematoxylin and eosin (H&E) and Oil Red O staining were performed. ResultsPhenotypic data showed that GPA decreased free fatty acid (FFA)-induced lipid buildup and high reactive oxygen species (ROS) levels, reversed the decrease in mitochondrial membrane potential (MMP), and increased the cellular reduced glutathione/oxidized glutathione disulfide (GSH/GSSG) ratio. GPA also reduces high glucose-induced lipid build-up and ROS production in C. elegans. Metabolomic analysis showed that GPA affected purine, lipid, and amino acid metabolism. Moreover, GPA inhibited xanthine oxidase (XOD), glutamate dehydrogenase (GLDH), fatty acid synthase (FAS), phosphorylation of P38 MAPK, and upregulated the expression of SIRT3 and CPT1A protein production to control lipid metabolism and produce antioxidant benefits in cells and golden hamsters. ConclusionCurrent evidence suggests that GPA can effectively regulate lipid metabolism and the oxidative stress response, and has the potential to prevent hyperlipidemia. This study also provided an effective method for evaluating the mechanism of action of GPA.

Phytochemical screening and biological evaluation of Greek sage (Salvia fruticosa Mill.) extracts

This study explores the influence of extraction solvents on the composition and bioactivity of Salvia fruticosa extracts. Ultrasound-assisted extraction with water, ethanol and their mixtures in variable proportions was used to produce four different extracts. An untargeted UPLC/MS‑based metabolomics was performed to discover metabolites profile variation between the extracts. In the analyzed samples, 2704 features had been detected, of which 95 were tentatively identified. The concentrations of the important metabolites, namely, caffeic acid, carnosic acid, carnosol, rosmarinic acid, salvianolic acid B and scutellarin, were determined, using UPLC-PDA methods. Rosmarinic acid was the dominant metabolite and antioxidant in all tested extracts, except the aqueous extract, in which scutellarin was the most abundant compound. The extracts and standards were examined for antioxidant activity and xanthine oxidase (XO) inhibitory activity. The most diverse in terms of chemical composition and rich in antioxidant compounds was 70% ethanolic extract and the strongest antioxidant was caffeic acid. All analyzed extracts showed the ability to inhibit XO activity, but the highest value was recorded for 30% ethanolic extract. Among tested standards, the most potent XO inhibitor was caffeic acid. The results suggest that the leaves of Greek sage are a source of natural XO inhibitors and may be an alternative to drugs produced by chemical synthesis.

Chemical Comparison and Identification of Xanthine Oxidase Inhibitors of Dioscoreae Hypoglaucae Rhizoma and Dioscoreae Spongiosae Rhizoma by Chemometric Analysis and Spectrum-Effect Relationship.

Dioscoreae hypoglaucae Rhizoma (DH) and Dioscoreae spongiosae Rhizoma (DS) are two similar Chinese herbal medicines derived from the Dioscorea family. DH and DS have been used as medicines in China and other Asian countries for a long time, but study on their phytochemicals and bioactive composition is limited. This present study aimed to compare the chemical compositions of DH and DS, and explore the anti-xanthine oxidase components based on chemometric analysis and spectrum-effect relationship. Firstly, an HPLC method was used to establish the chemical fingerprints of DH and DS samples, and nine common peaks were selected. Then, hierarchical clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were employed to compare and discriminate DH and DS samples based on the fingerprints data, and four steroidal saponins compounds (protodioscin, protogracillin, dioscin, gracillin) could be chemical markers responsible for the differences between DH and DS. Meanwhile, the anti-xanthine oxidase activities of these two herbal medicines were evaluated by xanthine oxidase inhibitory assay in vitro. Pearson correlation analysis and partial least squares regression analysis were subsequently used to investigate the spectrum-effect relationship between chemical fingerprints and xanthine oxidase inhibitory activities. The results showed that four steroidal saponins, including protodioscin, protogracillin, methyl protodioscin and pseudoprogracillin could be potential anti-xanthine oxidase compounds in DH and DS. Furthermore, the xanthine oxidase inhibitory activities of the four selected inhibitors were validated by anti-xanthine oxidase inhibitory assessment and molecular docking experiments. The present work provided evidence for understanding of the chemical differences and the discovery of the anti-xanthine oxidase constituent of DH and DS, which could be useful for quality evaluation and bioactive components screening of these two herbal medicines.

Maternal nano-titanium dioxide inhalation exposure alters placental cyclooxygenase and oxidant balance in a sexually dimorphic manner

The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulation, and thus impacts fetal growth and development. We have previously shown that nano-titanium dioxide (nano-TiO2) inhalation exposure during gestation decreased fetal female pup and placenta mass [1], which persists in the following generation [2]. In utero exposed females, once mated, their offspring's placentas had increased capacity for H2O2 production. Generation of oxidants such as hydrogen peroxide (H2O2), have been shown to impact cyclooxygenase activity, specifically metabolites such as prostacyclin (PGI2) or thromboxane (TXA2). Therefore, we hypothesized that maternal nano-TiO2 inhalation exposure during gestation results in alterations in placental production of prostacyclin and thromboxane mediated by enhanced H2O2 production in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols or filtered air (sham-control) from gestational day (GD) 10–19. Dams were euthanized on GD 20, and fetal serum and placental tissue were collected based on fetal sex. Fetal placental zones (junctional zone (JZ) and labyrinth zone (LZ)) were assessed for xanthine oxidoreductase (XOR) activity, H2O2, and catalase activity, as well as 6-keto-PGF1α and TXB2 levels. Nano-TiO2 exposed fetal female LZ demonstrated significantly greater XOR activity compared to exposed males. Exposed fetal female LZ also demonstrated significantly diminished catalase activity compared to sham-control females. Exposed fetal female LZ had significantly increased abundance of 6-keto-PGF1α compared to sham-control females and increased TXB2 compared to exposed males. In the aggregate these data indicate that maternal nano-TiO2 inhalation exposure has a greater impact on redox homeostasis and PGI2/TXA2 balance in the fetal female LZ. Future studies need to address if treatment with an XO inhibitor during gestation can prevent diminished fetal female growth during maternal nano-TiO2 inhalation exposure.

BCNO quantum dots-based ratiometric fluorescence platform integrated with portable device: Hypoxanthine sensing for on-site assessment of meat freshness with deep learning

Deep learning algorithms have been applied to digital image colorimetry (DIC) to improve color measurement and analysis, enabling the identification and quantification of analytes. In this work, we developed a smartphone-assisted platform for the detection of hypoxanthine (Hx) based on a ratiometric fluorescent probe (RF-probe) and deep learning algorithm for the first time with advantages of high sensitivity, in-field and simple operation, and accurate detection. Through an enzymatic cascade reaction, xanthine oxidase (XOD) degraded Hx to uric acid (UA) and H2O2, o-phenylenediamine (OPD) was converted to 2,3-diaminophenoxazine (DAP) by catalytic oxidation of H2O2 and OPD under horseradish peroxidase (HRP). The presence of DAP led to fluorescence quenching of BCNO quantum dots (BCNO QDs) at 440 nm and fluorescence enhancement of DAP at 570 nm due to the internal filtration effect (IFE). With the addition of Hx, the fluorescence color changed from blue to yellow. A good linear relationship was between I570/I440 and the Hx concentration in the range of 3-100 µM with a detection limit of 50 nM. Fluorescent color images of solution and test strips were acquired and extracted with a smartphone of our designed miniature device, which could be used to establish DIC for the detection of Hx with the linear relationship ranging from 0-100 μM and 0-40 μM, respectively. Then YOLOv5-assisted deep learning was applied to recognize and deal with the images, which offered improved accuracy, faster inference speed, flexibility, and efficient training. Therefore, our simple DIC platform was established for the in-field detection of Hx in real meat samples which was significant for the analysis of meat freshness and provided broad application potential for the analysis of other targets in food safety.

Molybdenum - a scoping review for Nordic Nutrition Recommendations 2023.

Molybdenum is an essential element in the form of the molybdenum cofactor (Moco). In humans, Moco is required for four enzymes: xanthine oxidase (XO), aldehyde oxidase, sulfite oxidase (SO), and mitochondrial amidoxime-reducing component (mARC). The enzymes are involved in the oxidation of purines to uric acid, metabolism of aromatic aldehydes and heterocyclic compounds, and in the catabolism of sulfur amino acids. Molybdenum cofactor deficiency is a rare autosomal recessive syndrome due to a defective synthesis of Moco, resulting in a deficiency of all the molybdoenzymes. There are no reports on clinical signs of dietary molybdenum deficiency in otherwise healthy humans. Water-soluble molybdate is efficiently absorbed from the digestive tract. The body retention is regulated by urinary excretion. Plasma molybdenum reflects long-term intake and 24-h urinary excretion is related to recent intake. There are no biochemical markers of molybdenum status. Cereal products are the main contributors to molybdenum dietary intake, estimated to 100-170 μg/day in Nordic studies. Little data are available on molybdenum toxicity in humans. A tolerable upper intake level of molybdenum has been based on reproductive toxicity in rats, but the effects have not been reproduced in more recent studies. The U.S. Institute of Medicine (IOM, present National Academy of Sciences, Engineering, and Medicine; NASEM) established a Recommended Dietary Allowance of 45 μg/day in adult men and women in 2001, based on a small study reporting urinary excretion in balance with intake at 22 μg/day. The European Food Safety Authority (EFSA) considered in 2013 the evidence to be insufficient to derive an Average Requirement and a Population Reference Intake, but proposed an Adequate Intake of 65 μg/day for adults.

Understanding Hyperuricemia: Pathogenesis, Potential Therapeutic Role of Bioactive Peptides, and Assessing Bioactive Peptide Advantages and Challenges.

Hyperuricemia is a medical condition characterized by an elevated level of serum uric acid, closely associated with other metabolic disorders, and its global incidence rate is increasing. Increased synthesis or decreased excretion of uric acid can lead to hyperuricemia. Protein peptides from various food sources have demonstrated potential in treating hyperuricemia, including marine organisms, ovalbumin, milk, nuts, rice, legumes, mushrooms, and protein-rich processing by-products. Through in vitro experiments and the establishment of cell or animal models, it has been proven that these peptides exhibit anti-hyperuricemia biological activities by inhibiting xanthine oxidase activity, downregulating key enzymes in purine metabolism, regulating the expression level of uric acid transporters, and restoring the composition of the intestinal flora. Protein peptides derived from food offer advantages such as a wide range of sources, significant therapeutic benefits, and minimal adverse effects. However, they also face challenges in terms of commercialization. The findings of this review contribute to a better understanding of hyperuricemia and peptides with hyperuricemia-alleviating activity. Furthermore, they provide a theoretical reference for developing new functional foods suitable for individuals with hyperuricemia.

Uric acid–reducing efficacy of Plectranthus amboinicus (Lour.) Spreng in mice with potassium oxonate-induced hyperuricemia

Plectranthus amboinicus (Lour.) Spreng is a type of Lamiaceae perennial herb that is widely used in folk treatments for respiratory and skin diseases. Notably, research on the hypouricemic effect of P. amboinicus is limited. This study investigated the uric acid–reducing efficacy of P. amboinicus in mice with potassium oxonate-induced hyperuricemia by performing an in vitro xanthine-oxidase-inhibition-activity-guided test of P. amboinicus extract (PAE) and its fractions. The ethyl acetate fraction (EAF) of PAE exhibited optimal efficacy in terms of the phenolic content, DPPH scavenging activity, and xanthine oxidase inhibition. We further demonstrated the uric acid–reducing activity of EAF in a mouse model of potassium bromate–induced hyperuricemia. The results can serve as a useful preclinical reference for researching the gout prevention effects of functional foods.
 Keywords: Plectranthus amboinicus (Lour.) Spreng, hyperuricemia, uric acid–reducing activity

Response to febuxostat according to clinical subtypes of hyperuricemia: a prospective cohort study in primary gout

BackgroundWhile xanthine oxidase inhibitors target uric acid production, renal urate underexcretion is the predominant subtypes in gout. This study was to compare treatment response to the XOI febuxostat in a gout cohort according to clinical subtypes of hyperuricemia.MethodsA prospective cohort study was conducted to compare the efficacy and safety of febuxostat (initially 20 mg daily, escalating to 40 mg daily if not at target) in 644 gout patients with the three major clinical subtypes for 12 weeks. Hyperuricemia was defined as the renal overload subtype, the renal underexcretion subtype, or the combined subtype based on UUE > or ≤ 600 mg/d/1.73 m2 and FEUA < or ≥ 5.5%. The primary endpoint was the rate of achieving serum urate (SU) < 6 mg/dL at week 12.ResultsFewer participants with combined subtype achieved the SU target, 45.5% compared with 64.8% with overload subtype (P = 0.007), and 56.6% with underexcretion subtype (P = 0.022). More participants with combined subtype (82%) had febuxostat escalated to 40 mg than those with overload (62%, P = 0.001) or underexcretion subtype (68%, P = 0.001). In all participants, combined subtype hyperuricemia (OR = 0.64, 95%CI 0.41–0.99, P = 0.048) and baseline SU (OR = 0.74, 95%CI 0.62–0.89, P = 0.001) were independently associated with lower rates of achieving SU target.ConclusionsPeople with combined subtype have a lower response to febuxostat, compared to those with either overload or underexcretion subtype. Assessment of hyperuricemia subtype may provide useful clinical data in predicting febuxostat response.

The role of melatonin in preventing amiodarone-induced rat liver damage.

Long-term exposure to amiodarone, an antiarrhythmic drug, can induce different organ damage, including liver. Cell damage included by amiodarone is a consequence of mitochondrial damage, reactive oxygen species production, and cell energy depletion leading to programmed cell death. In the present study, hepatoprotective potential of neurohormone melatonin (50mg/kg/day) was evaluated in a chronic experimental model of liver damage induced by a 4-week application of amiodarone (70mg/kg/day). The obtained results indicate that amiodarone induces an increase in xanthine oxidase activity, as well as the content of the lipid and protein oxidatively modified products and p53 levels. Microscopic analysis further corroborated the biochemical findings revealing hepatocyte degeneration, apoptosis, and occasional necrosis, with the activation of Kupffer cells. Coadministration of melatonin and amiodaron prevented an increase in certain damage associated parameters, due to its multiple targets. In conclusion, the application of melatonin together with amiodarone prevented an increase in tissue oxidative damage parameters and moderately prevented liver cell apoptosis, indicating that the damage of hepatocytes provoked by amiodarone supersedes the protective properties of melatonin in a given dose.

Xanthine or hypoxanthine or both may play therapeutical effect in Parkinson's disease through the endocannabinoid system

Parkinson's disease (PD) is a common neurodegenerative disorder. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra striata and the extensive accumulation of α-synuclein in different brain regions. The substantia nigra and striatum are brain regions with high expression of cannabinoid receptors, and the role of the endogenous cannabinoid system (ECS) has been explored in PD. The ECS may be a promising target for the treatment of PD. The correlation between PD and serum uric acid levels has been demonstrated in a large number of studies, but a causal relationship between the two has not been proven. Xanthine and hypoxanthine are upstream metabolite of uric acid, and they have been shown to be effective in relieving PD symptoms. Therefore, we hypothesized that xanthine or hypoxanthine or both may increase the inhibitory properties of GABAergic neurons by increasing the sensitivity of cannabinoid receptors on GABAergic neurons in the striatum, thereby activating the direct nigrostriatal pathway to ameliorate Parkinson's disease symptoms. The proposed hypothesis can be tested in animal and cellular intervention experiments. If this approach is found to be effective in improving PD symptoms with minimal adverse events, exogenous supplementation of xanthine/ hypoxanthine or the use of xanthine oxidase to block its metabolism to elevate hypoxanthine levels could potentially be an effective addition to PD therapy.

Inhibition of Xanthine Oxidase by Pyrazolone Derivatives Bearing a 4-(Furan-2-yl)benzoic Acid Moiety

The pyrazolone-based 4-(furan-2-yl)benzoic acids have been synthesized and studied as xanthine oxidase inhibitors. This enzyme is one of the therapeutic targets for the treatment of hyperuricemia and related diseases. The compounds studied have found to exhibit low micromolar IC50 values relative to the enzyme in vitro, depending on substituents in position 3 of the pyrazolone ring. However, the inhibitory effects observed are reduced in the presence of bovine serum albumin or Tween-80. Among the pyrazolone derivatives synthesized, 4-(5-((3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)methyl)furan-2-yl)benzoic acid has been found to be the most potent inhibitor of xanthine oxidase. Kinetic results have shown that this compound is a mixed-type inhibitor with higher affinity to the free enzyme than to the enzyme-substrate complex. The results of the molecular docking and molecular dynamics show that the carboxylic group of the inhibitor can form a salt bridge with Arg880 and a hydrogen bond with Thr1010. These interactions can be key factors in the enzyme-inhibitor complex stabilization.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1−2), two new geranyl glucosides (3−4), and nine known compounds (5–13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Signal-enhanced multi-core fiber-based WaveFlex biosensor for ultra-sensitive xanthine detection.

In this work, we introduce a novel multimode fiber (MMF) - seven core fiber (SCF) - MMF (MCM) optical fiber biosensor, also known as the WaveFlex biosensor (plasma wave assisted fiber biosensor), based on localized surface plasmon resonance (LSPR) for qualitative detection of xanthine. Xanthine is a purine base widely distributed in human blood and tissues, and commonly used as an indicator for various disease detections. The MCM sensor incorporates a tapered optical fiber structure, fabricated using the combiner manufacturing system (CMS), and is designed with SCF and MMF. By effectively harnessing LSPR, the sensor boosts the attachment points of biomolecules on the probe surface through immobilized tungsten disulfide (WS2)-thin layers, gold nanoparticles (AuNPs), and carbon nitride quantum dots (C3N-QDs). The functionalization of xanthine oxidase (XO) on the sensing probe further enhances the sensor's specificity. The proposed WaveFlex biosensor exhibits a remarkable sensitivity of 3.2 nm/mM and a low detection limit of 96.75 µM within the linear detection range of 100 - 900 µM. Moreover, the sensor probe demonstrates excellent reusability, reproducibility, stability, and selectivity. With its sensitivity, biocompatibility, and immense potential for detecting human serum and fish products, this WaveFlex biosensor presents a promising platform for future applications.

Eupatilin inhibits xanthine oxidase in vitro and attenuates hyperuricemia and renal injury in vivo

Uric acid (UA) is the final metabolite of purines in the liver that can cause hyperuricemia at high levels. The kidneys are the main excretory organs for UA. The excessive accumulation of UA in the kidneys causes the development of hyperuricemia that often leads to renal injury. Eupatilin (Eup) is a flavonoid natural product that possesses various pharmacological properties such as antioxidant, anti-cancer, and anti-inflammatory. We were interested in exploring the potential role of Eup in lowering UA and nephroprotective. We initially investigated the effects of Eup on xanthin oxidase (XOD) activity in vitro, followed by investigating its ability to lower UA levels, anti-inflammatory effects, nephroprotective effects, and the underlying mechanisms using hyperuricemia rats sustained at high UA level. The results showed that Eup had an inhibitory effect on XOD activity in vitro and significantly reduced serum UA, creatinine, BUN, IL-1β and IL-6 levels in hyperuricemic rats, ameliorating inflammation, renal oxidative stress and pathological injury. Furthermore, Eup inhibited ADA and XOD enzyme activities in the liver and serum and modulated GLUT9, URAT1 and ABCG2 protein expression in the kidneys and ileum. Our findings provide a scientific basis for suggesting Eup as an option for a potential treatment for hyperuricemia.

Antibacterial and Antioxidant Superoxide Anion Radical Inhibitors from Myrmecodia pendans: An In silico Study

Background: Background: Ant-nest (Myrmecodia pendans) is an epiphytic plant that can prevent several diseases, including bacterial infections. Diarrhea is caused by Escherichia coli bacteria, while infections in the oral cavity can be caused by Enterococcus faecalis bacteria. Antibacterial activity is also influenced by conditions of Reactive Oxygen Species (ROS). Antioxidants are needed to inhibit the formation of excess ROS in the body. Superoxide anion radicals are included in the generation of ROS, which is produced by several enzymes, such as nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase or commonly known as Nox and xanthine oxidase (XO). Objective: This study aimed to determine the potential of M. pendans as an antibacterial in vitro and in silico correlation in the formation of superoxide anion radicals. Methods: The compounds were obtained by column chromatography method, followed by a spectroscopic examination. In vitro test using the disc diffusion method and in silico test using AutoDock 4.2 program were conducted with positive control fosfomycin and allopurinol, tethered to MurA, Nox, and XO enzymes, and visualized using the Discovery Studio 2020. Results: Compound 1 (oleanolic acid) and compound 2 (pomolic acid) demonstrated antibacterial activity against E. coli but no activity against E. faecalis. Compound 3 (3-hydroxy-eupan-20,24-dien-26-oic acid) demonstrated no activity against these two bacteria. Based on the in silico results, compound 3 had the best binding energy affinity for all MurA, Nox, and XO enzymes of -6.89, -9.35, and -9.75 Kcal/mol, respectively. Similarly, compounds 1 and 2 had good binding energies for Nox protein of -9.29 Kcal/mol and -6.54 Kcal/mol and XO of -7.66 and -4.7 Kcal/mol, respectively. Conclusion: In vitro results against E. coli and E. faecalis bacteria showed inhibition by compounds 1 and 2 but not by compound 3. Meanwhile, in in silico analysis, all the compounds showed potential as an inhibitor of superoxide anion radicals generated by enzymes Nox and XO.

Virtual screening and structure optimization of xanthine oxidase inhibitory peptides from whole protein sequences of Pacific white shrimp via molecular docking.

Xanthine oxidase (XO) inhibitory peptides are safer than conventional pharmacological therapy in relieving hyperuricemia. However, traditional enzymatic hydrolysis, separation, and purification techniques for bio-active peptide preparation are time-consuming, inefficient, and labor-intensive. In this study, molecular docking and BLAST were used to virtually screen XO inhibitory peptides from whole protein sequences of Pacific white shrimp according to the bio-active peptides database, and the structure of peptides was optimized based on the structure-effective relationship. Seven new XO inhibitory peptides were virtual screened rapidly from Pacific white shrimp, and YNITGW (IC50=9.78±0.13mM) showed the strongest activity. The results of YNITGW optimization showed that the insertion of Trp residue in the middle position of peptides could effectively enhance the activity. This study revealed that screening and optimizing peptides by molecular docking were a novel and feasible method to obtain bio-active peptides.

Temporal change of serum xanthine oxidase levels and its relation to clinical outcome of severe traumatic brain injury: a prospective cohort study.

Xanthine oxidase (XO) may be involved in the induction of oxidative stress and inflammation. We measured serum XO levels at multiple days to determine whether it is associated with the severity and prognosis of severe traumatic brain injury (sTBI). In this prospective cohort study, we quantified serum XO levels in 112 sTBI patients and 112 controls. Serum XO levels of patients were measured at admission and at days 1, 3, 5, 7, and 10 after sTBI. Extended Glasgow outcome scale scores of 1-4 at post-trauma 180 days were defined as a poor prognosis. Multivariate analysis was employed to determine the relationship between poor prognosis and serum XO levels at multiple days. Serum XO levels were significantly increased at admission among patients, afterwards elevated gradually, peaked at day 3, and then diminished gradually until day 10, and were substantially higher during 10 days in patients than in controls. Serum XO levels at 6 different days were all correlated with admission Rotterdam computed tomography (CT) scores and Glasgow coma scale (GCS) scores. Serum XO levels at 6 different days were all substantially higher in patients with poor prognosis than in those with good prognosis. Serum XO levels at days 7 and 10, but not at days 1, 3, and 5, had significantly lower area under receiver operating characteristic (AUC) than those at admission. Serum XO levels at admission and at days 1 and 3, but not at day 5, were independently associated with 180-day poor prognosis. Prognostic prediction model containing GCS scores, Rotterdam CT scores, and serum XO levels at admission (or at days 1 and 3) showed substantially higher AUC than GCS scores and Rotterdam CT scores alone. The models were visually described using nomograms, which were comparatively stable under calibration curve and were relatively of clinical benefit under decision curve. Elevated serum XO levels during early period of sTBI are more closely associated with trauma severity and clinical adverse outcomes, assuming that serum XO may serve as a potential prognostic biomarker in sTBI.

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

Synthesis of 1,4-disubstituted-1,2,3-Triazole derivatives for investigation of inhibition and molecular docking studies against Xanthine Oxidase

Inhibitory capacity of extracts and main constituents of hop flowers

BackgroundHops (Humulus lupulus Linn.) produce flowers that are used on an industrial scale to impart sensory properties to beer and have some pharmacologic properties already published in the literature. Gout, type 2 diabetes and Alzheimer’s are diseases the appearance/aggravation of which is related to the action of enzymes such as xanthine oxidase, α-glucosidase and acetylcholinesterase, respectively, which are associated with oxidative stress. Our hypothesis is that the extracts and chemical constituents isolated from the flowers of hops act as enzyme inhibitors and scavenge free radicals. Hexane and methanol extracts were obtained from flowers of different cultivars produced in Brazil and from commercial pellets, with the contents of bitter acids and xanthohumol determined by high-performance liquid chromatography (HPLC), after QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) extraction and were evaluated for their pharmacologic properties.ResultsThe extracts and analytical standards showed a significant capacity against oxidative stress in all evaluated methods (DPPH·, ABTS·+, HO·). Xanthohumol and extracts with a high concentration of this compound demonstrated a strong capacity to inhibit the xanthine oxidase and significantly reduce the formation of uric acid. The results with the α-glucosidase revealed promising pharmacologic action for all samples, even more effective than the commercial drug (acarbose). The acetylcholinesterase inhibition assays were effective for hexane extracts and ICE-4, with values obtained close to the eserine.ConclusionIt can be concluded with the results obtained that extracts and patterns of hop flowers showed promising potential to combat oxidative stress and complementary treatment of gout, type 2 diabetes and Alzheimer’s disease.