Exploring the Phytochemical Composition and the Bioactive Properties of Malbec and Torrontés Wine Pomaces from the Calchaquíes Valleys (Argentina) for Their Sustainable Exploitation.

Hydroalcoholic extracts from Malbec and Torrontés wine pomaces (Vitis vinifera L.) originating from the high-altitude vineyards of Argentina's Calchaquí Valleys were characterized. Total phenolics, hydroxycinnamic acids, orthodiphenols, anthocyanins, non-flavonoid phenolics, total flavonoids, flavones/flavonols, flavanones/dihydroflavonols, and tannins were quantified through spectrophotometric methods, with the Malbec extract exhibiting higher concentrations in most of phytochemical groups when compared to Torrontés. HPLC-DAD identified more than 30 phenolic compounds in both extracts. Malbec displayed superior antiradical activity (ABTS cation, nitric oxide, and superoxide anion radicals), reduction power (iron, copper, and phosphomolybdenum), hypochlorite scavenging, and iron chelating ability compared to Torrontés. The cytotoxicity assessments revealed that Torrontés affected the viability of HT29-MTX and Caco-2 colon cancer cells by 70% and 50%, respectively, at the highest tested concentration (1 mg/mL). At the same time, both extracts did not demonstrate acute toxicity in Artemia salina or in red blood cell assays at 500 µg/mL. Both extracts inhibited the lipoxygenase enzyme (IC50: 154.7 and 784.7 µg/mL for Malbec and Torrontés), with Malbec also reducing the tyrosinase activity (IC50: 89.9 µg/mL), and neither inhibited the xanthine oxidase. The substantial phenolic content and diverse biological activities in the Calchaquí Valleys' pomaces underline their potentialities to be valorized for pharmaceutical, cosmetic, and food industries.

GKT137831 and hydrogen peroxide increase the release of 6-nitrodopamine from the human umbilical artery, rat-isolated right atrium, and rat-isolated vas deferens.

Introduction: The human umbilical artery (HUA), rat-isolated right atrium, and rat-isolated vas deferens present a basal release of 6-nitrodopamine (6-ND). The basal release of 6-ND from these tissues was significantly decreased (but not abolished) when the tissues were pre-incubated with Nω-nitro-L-arginine methyl ester (L-NAME). Methods: In this study, the effect of the pharmacological modulation of the redox environment on the basal release of 6-ND was investigated. The basal release of 6-ND was measured using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results and Discussion: Pre-incubation (30 min) of the tissues with GKT137831 (1 µM) caused a significant increase in the basal release of 6-ND from all tissues. In the HUA, pre-incubation with diphenyleneiodonium (DPI) (100 µM) also caused significant increases in the basal release of 6-ND. Preincubation of the HUA with hydrogen peroxide (H2O2) (100 µM) increased 6-ND basal release, whereas pre-incubation with catalase (1,000 U/mL) significantly decreased it. Pre-incubation of the HUA with superoxide dismutase (SOD) (250 U/mL; 30 min) also significantly increased the basal release of 6-ND. Preincubation of the HUA with either allopurinol (100 µM) or uric acid (1 mM) had no effect on the basal release of 6-ND. Pre-treatment of the HUA with L-NAME (100 µM) prevented the increase in the basal release of 6-ND induced by GKT137831, diphenyleneiodonium, and H2O2. The results obtained indicate a major role of endogenous H2O2 and peroxidases as modulators of 6- ND biosynthesis/release and a lack of peroxynitrite contribution.

Potential of milk-derived bioactive peptides as antidiabetic, antihypertensive, and xanthine oxidase inhibitors: a comprehensive bibliometric analysis and updated review.

Bioactive peptides consist of small protein fragments, which are inactive in their original conformation, and they become active when released from these through enzymatic hydrolysis or fermentation processes. The bioactivity of such peptides has been extensively reported in the literature as contributors to organic homeostasis processes, as well as in immunomodulation, organism defense against oxidative processes, among others. In this study, reports of the activity of BPs isolated from milk with the potential glycemic control, antihypertensive activity, and inhibitors of uric acid formation were compiled. A systematic literature review and bibliometric analysis were conducted, using the PICO strategy for the research. The temporal analysis of publications revealed a growing interest in the investigation of bioactive peptides with potential antidiabetic, antihypertensive, and xanthine oxidase inhibitory activities, using dairy sources as products for their extraction. The literature analysis also revealed an increase in research involving non-bovine dairy products for bioactive peptide extraction. The collaboration network among authors exhibited weaknesses in scientific cooperation. Regarding the analysis of keywords, the usage of terms such as "bioactive peptides", "antioxidant", "antihypertensive", and "diabetes" was evident, constituting the main research clusters. Peptides with low molecular weight, typically < 10 kDa, of hydrophobic nature with aliphatic and aromatic chains, have significant implications in molecular interactions for the required activities. Although there is a growing interest in the industry regarding the utilization of bioactive peptides as potential drugs, there is a need to address gaps related to elucidating their interactions with cellular targets and their use in human therapy.

Disordered Glucose Levels Are Associated with Xanthine Oxidase Activity in Overweight Type 2 Diabetic Women.

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of ß-cell function (HOMA-ß), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.

Allopurinol for fibromyalgia pain in adults: A randomized controlled trial.

BACKGROUND: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used in the treatment of hyperuricemia and gout. Because it is well known that purines exert multiple affects on pain transmission, we hypothesized that the inhibition of xanthine oxidase by allopurinol could be a valid strategy to treat pain in humans. This study aimed to compare the analgesic efficacy of oral allopurinol versus placebo as an adjuvant therapy in patients displaying fibromyalgia. METHODS: This randomized, double-blinded, placebo-controlled study included 60 women with the diagnosis of fibromyalgia. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 31) or placebo (n = 29) twice daily during 30 days. The patients were submitted to evaluation for pain sensitivity, anxiety, depression, and functional status before treatment, and 15 and 30 days thereafter. RESULTS: Oral administration of allopurinol 300 mg twice daily was ineffective in improving pain scores measured by several tools up to 30 days of treatment (P > 0.05). Additionally, no significant effects of allopurinol over anxiety, depressive symptoms, and functional status of fibromyalgia patients were observed in the present study. CONCLUSIONS: Although previous findings indicated that allopurinol could present intrinsic analgesic effects in both animals and humans, this study showed no benefit of the use of oral allopurinol as an adjuvant strategy during 30 days in women displaying fibromyalgia. However, considering previous promising results, new prospective studies are still valid to further investigate allopurinol and more selective purine derivatives in the management of pain syndromes.

Allopurinol attenuates postoperative pain and modulates the purinergic system in patients undergoing abdominal hysterectomy: a randomized controlled trial.

PURPOSE: Allopurinol is a potent inhibitor of the enzyme xanthine oxidase used primarily in the treatment of hyperuricemia and gout. The aim of this study was to compare the analgesic efficacy of preanesthetic allopurinol versus placebo on postoperative pain and anxiety in patients undergoing abdominal hysterectomy. METHODS: This is a prospective, double-blinded, placebo-controlled, randomized clinical trial. We investigated 54 patients scheduled to undergo elective abdominal hysterectomy. Patients were randomly assigned to receive either oral allopurinol 300 mg (n = 27) or placebo (n = 27) the night before and 1 h before surgery. Patients were submitted to evaluation of pain and anxiety before the treatment, for 24 h postoperatively, 30 and 90 days after surgery. Cerebrospinal fluid was collected at the time of the spinal anesthesia to perform the measurement of the central levels of purines. RESULTS: Preoperative administration of allopurinol was effective in reducing postoperative pain 2 h after surgery. Allopurinol caused a reduction of approximately 40% in pain scores measured by the visual analogue pain scale after surgery (p < 0.05). No differences were found between groups in anxiety scores after surgery. There was a significant change in the cerebrospinal fluid concentrations of xanthine and uric acid before surgery (p < 0.01). CONCLUSION: This study showed a short-term benefit of the use of allopurinol as a preanesthetic medication since it was related to a reduction on pain scores 2 h after surgery. The purinergic system is a potential target for new analgesic drugs. New studies investigating more selective purine derivatives in the management of pain should be performed. TRIAL NUMBER REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC #RBR-9pw58p.

Determination of the Antioxidant Activity of Samples of Tea and Commercial Sources of Vitamin C, Using an Enzymatic Biosensor.

Antioxidants are synthetic or natural compounds capable of preventing or delaying oxidative damage caused by chemical species that can oxidize cell biomolecules, such as proteins, membranes, and DNA, leading to the development of various pathologies, such as cancer, atherosclerosis, Parkinson, Alzheimer, and other diseases serious. In this study, an amperometric biosensor was used to determine the antioxidant activity of teas and effervescent products based on vitamin C, available on the market. A sensor composed of three electrodes was used. The performance of the following electrochemical mediators was evaluated: meldola blue combined with Reineck salt (MBRS), Prussian blue (PB), and cobalt phthalocyanine (CoPC), as well as the time of polymerization in the enzymatic immobilization process and the agitation process during chronoamperometric measurements. Prussian blue proved to be more efficient as a mediator for the desired purposes. After optimizing the construction stages of the biosensor, as well as the operational parameters, it presented stability for a period of 7 months. The results clearly indicate that the biosensor can be successfully used to detect fraud in products called "antioxidants" or even in drugs containing less ascorbic acid than indicated on the labels. The detection limit was set at 4.93 µmol·L-1.

Targeting Xanthine Oxidase by Natural Products as a Therapeutic Approach for Mental Disorders.

Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.

Actions of multiple doses of resveratrol on oxidative and inflammatory markers in plasma and brain of healthy and arthritic rats.

The actions of resveratrol in brain and plasma of rats with adjuvant-induced arthritis were investigated. Resveratrol was administered orally during a period of 23 days. A major concern of the present work was to explore an ample range of daily doses (10-200 mg/kg). Several oxidative and inflammatory markers were measured. Important effects of resveratrol treatment were the normalization of the plasma myeloperoxidase activity (inflammatory marker), the normalization of the brain xanthine oxidase activity (reactive oxygen species source) and the near-normalization of the catalase activity in the brain (antioxidant defence). These effects presented obvious dose dependencies in the range up to 200 mg/kg. Resveratrol also reduced protein and lipid damage within the lowest dose ranges investigated, and its action as a free radical scavenger activity was enhanced in brain mitochondria of arthritic rats. Resveratrol failed in restoring the diminished albumin levels and plasma protein thiols in arthritic rats. The latter, however, were substantially increased in healthy rats at low doses (up to 50 mg/kg), a sign of antioxidant action. This increase was reversed at higher doses, a sign of pro-oxidant action. The observations agree with the notion that low doses of resveratrol might be useful as an adjuvant to the conventional antirheumatic drugs.

Xanthine Oxidase Drives Hemolysis and Vascular Malfunction in Sickle Cell Disease.

OBJECTIVE: Chronic hemolysis is a hallmark of sickle cell disease (SCD) and a driver of vasculopathy; however, the mechanisms contributing to hemolysis remain incompletely understood. Although XO (xanthine oxidase) activity has been shown to be elevated in SCD, its role remains unknown. XO binds endothelium and generates oxidants as a byproduct of hypoxanthine and xanthine catabolism. We hypothesized that XO inhibition decreases oxidant production leading to less hemolysis. Approach and Results: Wild-type mice were bone marrow transplanted with control (AA) or sickle (SS) Townes bone marrow. After 12 weeks, mice were treated with 10 mg/kg per day of febuxostat (Uloric), Food and Drug Administration-approved XO inhibitor, for 10 weeks. Hematologic analysis demonstrated increased hematocrit, cellular hemoglobin, and red blood cells, with no change in reticulocyte percentage. Significant decreases in cell-free hemoglobin and increases in haptoglobin suggest XO inhibition decreased hemolysis. Myographic studies demonstrated improved pulmonary vascular dilation and blunted constriction, indicating improved pulmonary vasoreactivity, whereas pulmonary pressure and cardiac function were unaffected. The role of hepatic XO in SCD was evaluated by bone marrow transplanting hepatocyte-specific XO knockout mice with SS Townes bone marrow. However, hepatocyte-specific XO knockout, which results in >50% diminution in circulating XO, did not affect hemolysis levels or vascular function, suggesting hepatocyte-derived elevation of circulating XO is not the driver of hemolysis in SCD. CONCLUSIONS: Ten weeks of febuxostat treatment significantly decreased hemolysis and improved pulmonary vasoreactivity in a mouse model of SCD. Although hepatic XO accounts for >50% of circulating XO, it is not the source of XO driving hemolysis in SCD.

Uric Acid and Hypertension: An Update With Recommendations.

The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.

Enzymatic Bioautographic Methods.

Enzymatic bioautography enables the detection of enzyme inhibitors absorbed on a thin-layer chromatography plate. Therefore, it is an assay format that is particularly useful for the detection of inhibitors present in complex mixtures. The inhibition properties of compounds separated by thin-layer chromatography can be directly analyzed to produce an inhibition profile. Here, we describe the conditions to detect inhibitor of the enzymes xanthine oxidase and ß-glucosidase immobilized on agar gel.

Lychnophora pinaster ethanolic extract and its chemical constituents ameliorate hyperuricemia and related inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Lychnophora pinaster, known as "Brazilian arnica" is used in folk medicine as alcoholic extract to treat inflammation, pain, rheumatism and bruises. AIM OF THE STUDY: Evaluate the effects of the Lychnophora pinaster's ethanolic extract and its chemical constituents on inflammation and hyperuricemia. MATERIALS AND METHODS: Ethanolic and hexanic extracts were obtained from the aerial parts of L. pinaster. Sesquiterpene E-lychnophoric acid was isolated from hexanic extract and identified by RMN, GC/MS and IR. In vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. pinaster (40, 125, 375 mg/kg), E-lychnophoric acid and other constituents previous isolated from L. pinaster and identified in the ethanolic extract by HPLC/UV/DAD (rutin, quercetin and vitexina flavonoids, caffeic, cinnamic and chlorogenic acids, lupeol and stigmasterol, at dose of 15 mg/kg) were assayed by experimental model of oxonate-induced hyperuricemia in Swiss mice, liver xanthine oxidase (XOD) inhibition and by MSU-induced paw edema in mice. RESULTS: Ethanolic extract and all its components presented anti-hyperuricemic activity by inhibiting the hepatic xanthine oxidase activity. Ethanolic extract and its chemical constituents, except quercetin and vitexin, were able to reduce paw edema size induced by urate crystals. Hypouricemic and anti-inflammatory results obtained for the ethanolic extract (40, 125, 375 mg/kg) and E-lychnophoric acid (15 mg/kg) were similar those obtained for standard drugs, allopurinol (10 mg/kg) and indomethacin (3 mg/kg). CONCLUSION: Ethanolic extract and E-lychnophoric, chlorogenic, cinnamic and caffeic acids, rutin, lupeol and stigmasterol presented anti-inflammatory and anti-hyperuricemic actvities. These compounds are responsible for the activities presented by the ethanolic extract of L. pinaster. Ethanolic extract and its chemical constituents can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.

In vivo anti-hyperuricemic activity of sesquiterpene lactones from Lychnophora species

ABSTRACT Hyperuricemia is the main cause of gout, an inflammation induced by uric acid deposition in joints. Drugs available present side effects, so there is a need for new treatment alternatives. Lychnophora species are used in folk medicine to treat inflammation, rheumatism and muscle pain. Goyazensolide (10 mg/kg), eremantholide C (25 mg/kg) and lychnopholide (25 mg/kg), sesquiterpene lactones isolated from Lychnophora species were previously studied and showed anti-hyperuricemic effects in mice. However, the mechanisms of this effect were not elucidated. The methodology of this study consisted in treatment of hyperuricemic-induced rats, and comparison between control groups, clinically used anti-hyperuricemic drugs and sesquiterpene lactones. Urine and blood were collected for uric acid quantification. Xanthine oxidase inhibition was measured in liver homogenates. Results showed that all evaluated sesquiterpene lactones presented anti-hyperuricemic activity at the doses of 5 and 10 mg/kg and can act through one or both mechanisms, depending on the dose administrated. Goyazensolide and lychnopholide at dose of 5 mg/kg showed important uricosuric effect. Goyazensolide and lychnopholide at dose of 10 mg/kg, and eremantholide C (5 and 10 mg/kg) presented notable inhibition of hepatic xanthine oxidase activity and uricosuric effect. Thus, these sesquiterpene lactones are promising hypouricemic agent to treat hyperuricemia and gout.

A caffeine-supplemented diet modulates oxidative stress markers and prevents oxidative damage in the livers of Nile tilapia (Oreochromis niloticus) exposed to hypoxia.

Recent evidence has revealed the involvement of oxidative stress and oxidative damage with health impairment and mortality in fish exposed to hypoxia. Thus, natural compounds with antioxidant and free-radical-scavenging properties, such as caffeine, might help to prevent or reduce hepatic damage elicited by hypoxia. Thus, the aim of this study was to evaluate whether dietary supplementation with caffeine could prevent or reduce oxidative damage in the livers of Nile tilapia (Oreochromis niloticus) exposed to hypoxia. Hepatic reactive oxygen species, lipid peroxidation levels, and xanthine oxidase (XO) activity were higher in fish exposed to hypoxia compared with normoxia. Hepatic catalase, glutathione peroxidase, and glutathione S-transferase activities, as well as the antioxidant capacity against peroxyl radical levels, were lower in fish exposed to hypoxia compared with normoxia. No significant difference between groups was observed regarding hepatic superoxide dismutase activity. Dietary supplementation with 8% caffeine prevented all alterations elicited by hypoxia. Based on this evidence, the use of dietary supplementation with 8% caffeine can be an interesting approach to preventing hepatic lipid damage and impairment of the antioxidant defense system elicited by hypoxia, and this effect can be mediated by protective effects on XO activity.

The antioxidant system in the soleus muscle of growing rats is stimulated by the administration of a low-protein/high-carbohydrate diet.

The aim of this study was to evaluate the generation of reactive oxygen species (ROS) by xanthine oxidase (XO), the enzymatic antioxidant system and oxidative damage in soleus and extensor digitorum longus (EDL) muscles of growing rats fed a low-protein, high-carbohydrate (LPHC; 6% protein, 74% carbohydrate) diet for 15 days. The LPHC diet increased the total antioxidant capacity by 45% and the activities of glutathione peroxidase (GPx), glutathione reductase and catalase in the soleus muscles. There was an increase in the carbonylated proteins with no increase thiobarbituric acid reactive substances (TBARS), although the XO activity had increased 20%. In EDL muscles, the LPHC diet increased XO activity by 66% and the TBARS levels by 80%, and only GPx had its activity increased. These results suggest that the enzymatic antioxidant system of the soleus muscle has a better response to the increase of ROS production stimulated by LPHC diet.

On the Possible Chemical Justification of the Ethnobotanical Use of Hyptis obtusiflora in Amazonian Ecuador.

In rural areas of Latin America, Hyptis infusions are very popular. Hyptis obtusiflora extends from Mexico throughout Central America to Bolivia and Peru. It has added value in Ecuador where it has been used by different ethnic groups. We aimed to learn about the traditional knowledge of ancient Kichwa cultures about this plant, and to contrast this knowledge with the published information organized in occidental databases. We proposed to use traditional knowledge as a source of innovation for social development. Our specific objectives were to catalogue the uses of H. obtusiflora in the community, to prospect on the bibliography on a possible chemical justification for its medicinal use, to propose new products for development, and to give arguments for biodiversity conservation. An ethnobotanical survey was made and a Prisma 2009 Flow Diagram was then followed for scientific validation. We rescued data that are novel contributions for the ethnobotany at the national level. The catalogued main activity of anti-inflammation can be related to the terpene composition and the inhibition of xanthine oxidase. This opens the possibility of researching the extract of this plant as an alternative to allopurinol or uricosuric drugs. This is a concrete example of an argument for biodiversity conservation.

Improved Methods for the Rapid Formation and Prevention of Advanced Glycation End Products (AGEs) In Vitro by Coupling to the Hypoxanthine/Xanthine Oxidase Assay System.

Advanced glycation end products (AGEs) represent a set of molecules that contribute directly to the initiation and aggravation of diseases associated with ageing. AGEs are produced by the reaction between reducing sugars (or α-dicarbonyl compounds), proteins, and amino acid residues. Previous in vitro methods using non-enzymatic procedures described in the literature require an incubation period of 1⁻3 weeks to generate AGEs. In this study, the reaction time for the formation of AGEs (48 and 3 h) was significantly reduced by adaptation of methods previously described in the literature and coupling them to the free radical generation system termed hypoxanthine/xanthine oxidase assay. The incorporation of this assay into the experimental system accelerated the production of AGEs as a result of the formation of reactive oxygen species (ROS), as shown by increased fluorescence. The capacity of different classes of chemical compounds (aminoguanidine, chlorogenic acid, rutin, and methanol extracts of Hancornia speciosa Gomes) to inhibit protein glycation by acting as scavenging agents of α-dicarbonyl species was evaluated. Aminoguanidine and, especially, rutin identified in the leaf extracts of H. speciosa Gomes showed a high capacity to act as scavengers of reactive carbonyl species RCS-trapping, resulting in the inhibition of AGEs formation.

An Antioxidant Potential, Quantum-Chemical and Molecular Docking Study of the Major Chemical Constituents Present in the Leaves of Curatella americana Linn.

Reactive oxygen species (ROS) are continuously generated in the normal biological systems, primarily by enzymes as xanthine oxidase (XO). The inappropriate scavenging or inhibition of ROS has been considered to be linked with aging, inflammatory disorders, and chronic diseases. Therefore, many plants and their products have been investigated as natural antioxidants for their potential use in preventive medicine. The leaves and bark extracts of Curatella americana Linn. were described in scientific research as anti-inflammatory, vasodilator, anti-ulcerogenic, and hypolipidemic effects. So, the aim of this study was to evaluate the antioxidant potentials of leaf hydroalcoholic extract from C. americana (HECA) through the scavenging DPPH assay and their main chemical constituents, evaluated by the following quantum chemical approaches (DFT B3LYP/6-31G**): Maps of Molecular Electrostatic Potential (MEP), Frontier Orbital's (HOMO and LUMO) followed by multivariate analysis and molecular docking simulations with the xanthine oxidase enzyme. The hydroalcoholic extract showed significant antioxidant activity by free radical scavenging probably due to the great presence of flavonoids, which were grouped in the PCA and HCA analysis with the standard gallic acid. In the molecular docking study, the compounds studied presented the binding free energy (ΔG) values close each other, due to the similar interactions with amino acids residues at the activity site. The descriptors Gap and softness were important to characterize the molecules with antioxidant potential by capturing oxygen radicals.

Xanthine oxidase inhibitors and sepsis.

Xanthine oxidase activation occurs in sepsis and results in the generation of uric acid (UrAc) and reactive oxygen species (ROS). We aimed to evaluate the effect of xanthine oxidase inhibitors (XOis) in rats stimulated with lipopolysaccharide (LPS). LPS (10 mg/kg) was administered intraperitoneally (i.p.) immediately after allopurinol (Alo, 2 mg/kg) or febuxostat (Feb, 1 mg/kg) every 24 h for 3 days. To increase UrAc levels, oxonic acid (Oxo) was administered by gavage (750 mg/kg per day) for 5 days. Animals were divided into the following 10 groups (n = 6 each): (1) Control, (2) Alo, (3) Feb, (4) LPS, (5) LPSAlo, (6) LPSFeb, (7) Oxo, (8) OxoLPS, (9) OxoLPSAlo, and (10) OxoLPSFeb. Feb with or without Oxo did not aggravate sepsis. LPS administration (with or without Oxo) significantly decreased the creatinine clearance (ClCr) in LPSAlo (60%, P < 0.01) versus LPS (44%, P < 0.05) and LPSFeb (35%, P < 0.05). Furthermore, a significant increase in mortality was observed with LPSAlo (28/34, 82%) compared to LPS treatment alone (10/16, 63%) and LPSFeb (11/17, 65%, P < 0.05). In addition, increased levels of thiobarbituric acid reactive substances (TBARS), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 were observed at 72 h compared to the groups that received LPS and LPSFeb with or without Oxo. In this study, coadministration of Alo in LPS-induced experimental sepsis aggravated septic shock, leading to mortality, renal function impairment, and high ROS and proinflammatory IL levels. In contrast, administration of Feb did not potentiate sepsis, probably because it did not interfere with other metabolic events.