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Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFGs physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk.

Enzymes are biologically active complex protein molecules that catalyze most chemical reactions in living organisms, and their inhibitors accelerate biological processes. This review emphasizes medicinal food plants and their isolated chemicals inhibiting clinically important enzymes in common diseases. A mechanistic overview was investigated to explain the mechanism of these food bases enzyme inhibitors. The enzyme inhibition potential of medicinal food plants and their isolated substances was searched in Ovid, PubMed, Science Direct, Scopus, and Google Scholar. Cholinesterase, amylase, glucosidase, xanthine oxidase, tyrosinase, urease, lipoxygenase, and others were inhibited by crude extracts, solvent fractions, or isolated pure chemicals from medicinal food plants. Several natural compounds have shown tyrosinase inhibition potential, including quercetin, glabridin, phloretin-4-O-β-D-glucopyranoside, lupinalbin, and others. Some of these compounds' inhibitory kinetics and molecular mechanisms are also discussed. Phenolics and flavonoids inhibit enzyme activity best among the secondary metabolites investigated. Several studies showed flavonoids' significant antioxidant and anti-inflammatory activities, highlighting their medicinal potential. Overall, many medicinal food plants, their crude extracts/fractions, and isolated compounds have been studied, and some promising compounds depending on the enzyme have been found. Still, more studies are recommended to derive potential pharmacologically active functional foods. [ABSTRACT FROM AUTHOR]

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT. Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015. [ABSTRACT FROM AUTHOR]

ABSTRACT Yak milk is abundant in casein, which can generate a variety of bioactive peptides through enzymatic hydrolysis. However, the influence of enzymatic hydrolysis on the structural properties of yak casein and its inhibitory effects on xanthine oxidase (XOD) remain largely unexplored. This study demonstrated that when yak casein was subjected to treatment with flavourzyme, the degree of hydrolysis progressively increased over time, resulting in the fragmentation of the casein's flake‐like structure into smaller particles. Circular dichroism analysis revealed that after 4 h of enzymatic treatment, there was an elevation in the β‐sheet content of the yak casein hydrolysate, while other secondary structure elements diminished. Furthermore, flavourzyme treatment induced modifications in the tertiary structure of yak casein. The study also examined the impact of varying hydrolysis durations on XOD inhibitory activity, discovering that the hydrolysate obtained after 3 h displayed the highest inhibition on XOD, with an inhibition rate of (40.63 ± 3.36) %. Additionally, the fraction of the hydrolysate with a molecular weight exceeding 3 kDa demonstrated enhanced XOD inhibitory activity. This study is the first to investigate how varying hydrolysis durations with flavourzyme affect the structural characteristics of yak casein and its XOD inhibitory activity. [ABSTRACT FROM AUTHOR]

AbstractSources of milk fat globule membrane (MFGM) are desirable to include in infant milk formula (IMF) to mimic the composition and functionality of human milk MFGM. MFGM in its natural form consists of a trilayer structure containing lipids (e.g., cholesterol, phospholipids, gangliosides, ceramides), proteins (e.g., butyrophilin, xanthine oxidase, mucin-1, adipophilin) and glycans (e.g., sialic acid). Components of MFGM have been associated with various biological benefit areas including intestinal, neurocognitive, and immune health. There are many aspects to consider when supplementing IMF with MFGM ingredients, of which the major ones are highlighted and critiqued in this review from an industrial research perspective. Features include compositional unknowns, discussion on how best to incorporate MFGM to IMF, analytical method needs, biological function unknowns, and considerations on how best to communicate MFGM in different contexts. It is hoped that by identifying the key scientific gaps outstanding in this subject area, collective efforts can proceed to ensure the potential impact of MFGM on infant health is realized. [ABSTRACT FROM AUTHOR]

Background/Objectives: Hyperuricemia (HUA) is a common metabolic disease caused by purine metabolic disorders in the body. Portulaca oleracea L. (PO) is an edible wild vegetable. Methods: In this study, the regulatory effect of PO on HUA and its potential mechanism were initially elucidated through network pharmacology and experimental validation. Results: The results showed that PO from Sichuan province was superior to the plant collected from other habitats in inhibiting xanthine oxidase (XOD) activity. Berberine and stachydrine were isolated and identified from PO for the first time by UPLC-Q-Exactive Orbitrap MS. The potential molecular targets and related signaling pathways were predicted by network pharmacology and molecular docking techniques. Molecular docking showed that berberine had strong docking activity with XOD, and the results of in vitro experiments verified this prediction. Through experimental analysis of HUA mice, we found that PO can reduce the production of uric acid (UA) in the organism by inhibiting XOD activity. On the other hand, PO can reduce the body 's reabsorption of urate and aid in its excretion out of the body by inhibiting the urate transporter proteins (GLUT9, URAT1) and promoting the high expression of urate excretory protein (ABCG2). The results of H/E staining showed that, compared with the positive drug (allopurinol and benzbromarone) group, there was no obvious renal injury in the middle- and high-dose groups of PO extract. Conclusions: In summary, our findings reveal the potential of wild plant PO as a functional food for the treatment of hyperuricemia. [ABSTRACT FROM AUTHOR]

Fluorescent markers play important roles in spectroscopic and microscopic research techniques and are broadly used in basic and applied sciences. We have obtained markers with fluorescent properties, two etheno derivatives of 2-aminopurine, as follows: 1,N2-etheno-2-aminopurine (1,N2-ε2APu, I) and N2,3-etheno-2-aminopurine (N2,3-ε2APu, II). In the present paper, we investigate their interaction with two key enzymes of purine metabolism, purine nucleoside phosphorylase (PNP), and xanthine oxidase (XO), using diffraction of X-rays on protein crystals, isothermal titration calorimetry, and fluorescence spectroscopy. Crystals were obtained and structures were solved for WT PNP and D204N-PNP mutant in a complex with N2,3-ε2APu (II). In the case of WT PNP—1,N2-ε2APu (I) complex, the electron density corresponding to the ligand could not be identified in the active site. Small electron density bobbles may indicate that the ligand binds to the active site of a small number of molecules. On the basis of spectroscopic studies in solution, we found that, in contrast to PNP, 1,N2-ε2APu (I) is the ligand with better affinity to XO. Enzymatic oxidation of (I) leads to a marked increase in fluorescence near 400 nm. Hence, we have developed a new method to determine XO activity in biological material, particularly suitable for milk analysis. [ABSTRACT FROM AUTHOR]

In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1β, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1β, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail. [ABSTRACT FROM AUTHOR]

Olea europaea L. (OEL) fruits play a significant role in the Mediterranean diet. OEL fruits contain abundant bioactive components and have been reported to possess potential antioxidant and xanthine oxidase (XOD) inhibition effects. However, the active components for XOD inhibition effects and related mechanisms are still unclear. In this study, the antioxidant activity of OEL fruits was assessed and showed a good effect on antioxidants. After that, the XOD inhibition effects of OEL fruits were investigated. The results indicated that OEL fruits also have a good impact on inhibiting XOD, with IC50 values of 208.2 ± 1.58 μg/mL. Under the optimal experimental conditions, six potential XOD ligands in OEL fruits were screened out and three phenylethanol analogues were identified (hydroxytyrosol, 3,4-dihydroxy phenyl ethyl acetate, oleuropein). Compared to the inactivated group, 3,4-dihydroxy phenyl ethyl acetate had the highest affinity, indicating it might be the main component of the OEL fruits that inhibit XOD. Molecular docking results elucidated that the potential active components mainly form hydrogen bonds with XOD. The results showed that OEL fruits possessed potential antioxidant and XOD inhibitory effects and that the affinity ultrafiltration (UF) method is an effective method to screen potential ligands for XOD from natural products. [ABSTRACT FROM AUTHOR]

Cardiovascular functions in diabetes greatly depend on constitutive NOS (cNOS) activity. A comparative study of the effects of a steroid hormone ecdysterone and enalapril, an ACE inhibitor widely used to treat cardiac disorders on cNOS, inducible NOS (iNOS), xanthine oxidoreductase (XOR) activity, RNS, ROS, and lipid peroxidation in heart tissue in experimental diabetes was conducted. The rat model of diabetes was established by streptozotocin injection. NOS activity, NO2−, NO3−, uric acid, nitrosothiols, hydroperoxide, superoxide, and diene conjugate formation were studied spectrophotomerically. In diabetes, cNOS downregulation correlated with a dramatic fall of NO2− production and ~4.5-fold elevation of nitrosothiols, which agreed with a steep rise of iNOS activity, while NO3− remained close to control. Dramatic activation of XOR was observed, which correlated with the elevation of both superoxide production and nitrate reductase activity and resulted in strong lipid peroxidation. Ecdysterone and enalapril differently affected RNS metabolism. Ecdysterone moderately restored cNOS but strongly suppressed iNOS, which resulted in the reduction of NO3−, but full restoration of NO2− production. Enalapril better restored cNOS but less effectively suppressed iNOS, which promoted NO3− formation. Both drugs similarly inhibited XOR, which equally alleviated oxidative stress and lipid peroxidation. The synergistic action of iNOS and XOR was a plausible explanation for strong lipid peroxidation, abolished by the inhibition of iNOS and XOR by ecdysterone or enalapril. Complementary effects of ecdysterone and enalapril on cNOS, iNOS, and RNS are a promising basis for their combined use in the treatment of cardiovascular disorders caused by cNOS dysfunction in diabetes. [ABSTRACT FROM AUTHOR]

Sodium fluoride (NaF) ingestion has several detrimental effects in humans and rodents. NaF mechanisms of toxicity include perturbation of intracellular redox homeostasis and apoptosis. Betaine (BET) is a modified amino acid with anti-inflammatory, antioxidant, and anti-apoptotic properties. This study investigates BET's effect on NaF-induced hepatorenal toxicities in rats. Experimental rats (n = 30) were randomly assigned to groups (n = 6) and treated by gavage for 28 days. Group I (2 mL of distilled water), Group II (NaF: 9 mg/kg) alone, Group III: (BET: 100 mg/kg), Group IV: (NaF: 9 mg/kg and BET 1: 50 mg/kg), and Group V: (NaF: 9 mg/kg and BET 2: 100 mg/kg). Our findings revealed significantly (p < 0.05) increased hepatic transaminase activities alongside creatinine and urea levels following NaF-alone treatment in addition to increased oxidative status, lipid peroxidation, reactive oxygen and nitrogen species, decreased superoxide dismutase, catalase, glutathione-s-transferase, glutathione peroxidase, glutathione, and total sulfhydryl groups. The reduced levels of nuclear factor erythroid 2-related factor-2 and the activities of heme oxygenase-1, thioredoxin, and thioredoxin reductase in NaF-alone treated rats equally compromised cellular molecular responses to oxidative stress. Also, NaF increased (p < 0.05) hepatorenal inflammatory biomarkers-nitric oxide, interleukin-10, myeloperoxidase, and xanthine oxidase. Furthermore, caspase-3 and caspase-9 were increased (p < 0.05) in rats treated with NaF alone. Contrastingly, BET was observed to alleviate the harmful effects of NaF. Treatment with BET mitigated NaF-induced oxido-inflammatory responses and apoptosis in the experimental rat's hepatorenal system. The study demonstrates the potential of BET to abate NaF-induced hepatorenal toxicity. [ABSTRACT FROM AUTHOR]

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Chaenomeles speciosa (Sweet) Nakai (C. speciosa) is a traditional Chinese herbal medicine that possesses not only abundant nutritional value but also significant medicinal properties. The extracts of C. speciosa fruits effectively reduce urate levels, but the specific chemical constituents responsible for this effect in C. speciosa fruits are still unknown. Therefore, this study aims to investigate and analyze the structure–activity relationships of these constituents to better understand their ability to lower uric acid. Activity-guided fractionation and purification processes were used to isolate compounds with xanthine oxidase (XO) inhibitory activity from C. speciosa fruits, resulting in three extracts: petroleum ether, ethyl acetate, and n-butanol. The ethyl acetate and n-butanol fractions showed strong activity and underwent further separation and purification using chromatographic techniques. Twenty-four compounds were isolated and identified, with nine showing potent activity, including chlorogenic acid, methyl chlorogenate, butyl chlorogenate, ethyl chlorogenate, cryptochlorogenic acid methyl ester, caffeic acid, p-coumaric acid, benzoic acid and protocatechuic acid. The docking analysis showed that these compounds interacted with amino acid residues in the active site of XO through hydrogen bonding and hydrophobic interactions. These findings suggest that these compounds help reduce uric acid in C. speciosa, supporting further investigation into their mechanism of action. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XOD) is a key enzyme that promotes the oxidation of xanthine/hypoxanthine to form uric acid, and the accumulation of uric acid leads to hyperuricaemia. The prevalence of gout caused by hyperuricaemia is increasing year by year. TAOZHI (TZ) can be used for the treatment of rheumatic arthralgia due to qi stagnation and blood stasis and contains a large number of polyphenolic components. The aim of this study was to investigate the relationship between chromatograms and XOD inhibition of 21 batches of TZ total polyphenol extract samples. Chemometric methods such as grey correlation analysis, bivariate correlation analysis, and partial least squares regression were used to identify the active ingredient groups in the total polyphenol extracts of TZ, which were validated using molecular docking techniques. The total polyphenol content contained in the 21 batches did not differ significantly, and all batches showed inhibitory effects on XOD. Spectroeffect correlation analysis showed that the inhibitory effect of TZ on XOD activity was the result of the synergistic effect of multiple components, and the active component groups screened to inhibit XOD were F2 (4-O-Caffeoylquinic acid), F4, and F10 (naringenin). The molecular docking results showed that the binding energies of all nine dockings were lower than −7.5 kcal/mol, and the binding modes included hydrogen bonding, hydrophobic forces, salt bridges, and π-staking, and the small molecules might exert their pharmacological effects by binding to XOD through the residue sites of the amino acids, such as threonine, arginine, and leucine. This study provides some theoretical basis for the development and utilisation of TZ total polyphenols. [ABSTRACT FROM AUTHOR]

Terpenes are plant secondary metabolites known for their anti-inflammatory and antioxidant activities. According to ethnobotanical knowledge, Rhododendron luteum Sweet was used in traditional medicine against inflammation. The present study was conducted to determine the triterpene profile and antioxidant and anti-inflammatory activity of supercritical CO2 (SC-CO2) extracts of Rhododendron luteum Sweet flower (RLF). An LC-APCI-MS/MS analysis showed the presence of eight pentacyclic triterpenes and one phytosterol in the extracts obtained with pure CO2 as well as CO2 with the addition of aqueous ethanol as a co-solvent. Among the compounds detected, oleanolic/ursolic acid, β-sitosterol and 3β-taraxerol were the most abundant. The extract obtained with pure SC-CO2 was additionally subjected to HS-SPME-GC-FID-MS, which revealed more than 100 volatiles, mainly eugenol, β-phenylethanol, dodecane, β-caryophyllene, estragole and (Z)- and (E)-cinnamyl alcohol, followed by δ-cadinene. The extracts demonstrated significant hyaluronidase inhibition and exhibited varying modes of lipoxygenase and xanthine oxidase inhibitory activities. The studies of RLF have shown that their SC-CO2 extracts can be a rich source of triterpenes with anti-inflammatory potential. [ABSTRACT FROM AUTHOR]

The difference on inhibitory effects of bioflavonoids inhibiting XOD activity assayed by varying test methods cause of us to be further in consideration. The reported test method creating a micro‐environment surrounding XOD in the absence of ⋅O2−, which is seemly different from the assay in vivo. So, the vitro test method for assaying XOD activity is necessary to be improved for selection of potential inhibitors in the presence of ⋅O2−. The inhibitory results demonstrated that bioflavonoids of MY, DMY, QUE and LUT are capable to be on effective IC50 values, but others are not. As well, their resulting inhibitions determined by the improved test method are much less than that reported in the literature, indicating that their chemical affinities with XOD become weaker. Moreover, DMY assayed on the inhibitions of XOD in the improved test method performs to be a better inhibitor, as compared to the assay of the reported test methods. Abasing on the transformation of DMY into MY in the presence of ⋅O2−, the good inhibition of DMY on XOD activity can be explained by the synergistic effect of MY. [ABSTRACT FROM AUTHOR]

Xanthine oxidase (XO) is an enzyme that converts hypoxanthine into xanthine and xanthine into uric acid, which is then eliminated by the kidneys. Serum XO has been linked to diabetes, hypertension, liver dysfunction, and cardiovascular diseases. However, limited information exists on the relationship between serum XO activity and MetS. This study aimed to analyze the relationship between XO activity and metabolic syndrome (MetS) and its components in an adult population group in Bangladesh A total of 601 participants aged ≥18 years were included in the study. MetS was defined based on the criteria set by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Serum XO activity was measured using the enzyme-linked immunosorbent assay (ELISA), while other biochemical parameters were measured using colorimetric methods. The relationship between serum XO and MetS levels was determined through multivariate logistic regression analysis. Serum XO activity was found to be significantly higher in females (6.17 ± 3.77 U/L) as compared to males (4.00 ± 2.77 U/L) (p < 0.001). Furthermore, participants with MetS had significantly higher mean levels of serum XO (5.34 ± 3.39 U/L) than those without MetS (3.86 ± 2.90 U/L) (p < 0.001). The prevalence of MetS and its components, such as blood pressure and blood glucose increased across the XO quartiles (p < 0.001). Regression analysis indicated that XO activity was significantly and independently associated with the prevalence of MetS (at least p < 0.05 for all cases) and its components, including elevated blood pressure, high blood glucose, and low HDL-C (at least p < 0.05 for all cases). In conclusion, individuals with MetS had significantly higher XO levels than those without MetS. Serum XO activity showed an independent association with MetS and some of its components. Therefore, XO might serve as a useful marker of MetS. Prospective studies are needed to determine the underlying mechanisms linking XO and MetS. [ABSTRACT FROM AUTHOR]

Rat H9c2 cardiomyocytes overexpressing the abscisic acid (ABA) hormone receptors LANCL1 and LANCL2 have an increased mitochondrial proton gradient, respiration, and vitality after hypoxia/reoxygenation. Our aim was to investigate the role of the ABA/LANCL1-2 system in ROS turnover in H9c2 cells. H9c2 cells were retrovirally infected to induce the overexpression or silencing of LANCL1 and LANCL2, without or with the concomitant silencing of the transcription factor ERRα. Enzymes involved in radical production or scavenging were studied by qRT-PCR and Western blot. The mitochondrial proton gradient and ROS were measured with specific fluorescent probes. ROS-generating enzymes decreased, ROS-scavenging enzymes increased, and mitochondrial ROS were reduced in LANCL1/2-overexpressing vs. control cells infected with the empty vector, while the opposite occurred in LANCL1/2-silenced cells. The knockdown of ERRα abrogated all beneficial effects on ROS turnover in LANCL1/2 overexpressing cells. Taken together, these results indicate that the ABA/LANCL1-2 system controls ROS turnover in H9c2 via ERRα. The ABA/LANCL system emerges as a promising target to improve cardiomyocyte mitochondrial function and resilience to oxidative stress. [ABSTRACT FROM AUTHOR]

Trace elements such as cobalt (Co), molybdenum (Mo), and zinc (Zn) play necessary roles in different biological functions. Co is a microelement that influences the vascular system. Mo works as an enzymatic cofactor of three enzymes (aldehyde oxidase, sulfite oxidase, and xanthine oxidase dehydrogenase). However, these elements are difficult to detect, since the analytical methods developed have a high cost, which restrict their applicability. In this sense, fluorescent sensors are an alternative for detecting trace elements, such as Mo4+ ions. Herein, a new multichannel trace elements sensor has been proposed to detect Mo entities. In this sense, two different N-CQDs were synthesized and fully characterized. The N-CQDs presented quantum yield values of 25.93% and 6.02% and excellent solubility in water. Also, a mixture of these two carbon-based nanoparticles was used to identify and to quantify Mo in water between seven different trace elements. The method was found to reach 1.28 and 3.88 ppm for limit of detection (LOD) and quantification (LOQ), respectively. To further verify the potential of the detection platform, the multichannel sensor was applied to identify the different concentrations of metal ions (Fe2+, Co2+, Mn2+, Cu2+, Zn2+, Mg2+, and Mo4+) in water. The data matrix was treated using different algorithms, such as K-Means and Discriminant Analysis (DA). The detection strategy has successfully identified the molybdenum ions at 5 ppm. This result shows the potential application of a multichannel sensor toward the detection of Mo entities, since it is comparable with the molybdenum test already available on the market. [ABSTRACT FROM AUTHOR]

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of •OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 109 M−1 s−1), and exhibits potent •OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation. [ABSTRACT FROM AUTHOR]

Kaempferia subglobosa is a perennial medicinal plant in the Zingiberaceae family, identified as a new species in January 2024. To uncover the biological benefits of K. subglobosa and its compounds, investigation of the metabolites of the roots and rhizomes, yielded three new monoterpene‐chalcone conjugates, the globosones A–C, representing a rare metabolite group within the Zingiberaceae, along with six known compounds. The biogenetic pathway for the globosones involves an oxidative [3+2] cycloaddition between α‐phellandrene and 4’‐methoxy‐4,2’,6’‐trihydroxychalcone. Biological testing revealed potent xanthine oxidase (XO) inhibition by globosones A and B, with IC50 values of 7.0±1.0 and 3.0±0.2 μM, respectively, surpassing the positive control drug allopurinol (IC50 7.2±0.1 μM). Globosones A–C also showed good aromatase inhibition (IC50 3.0–3.5 μM). Molecular docking studies indicated that globosones A and B may inhibit xanthine oxidase through binding at the FAD domain site. The physicochemical properties of these isolates suggest that they possess characteristics suitable for additional biological assessment in more advanced test systems. This study enhances an understanding of monoterpene‐chalcone conjugate inhibitors of XO, and offers preliminary insights into the metabolites and bioactivities of K. subglobosa, uncovering potent biological activities associated with this newly discovered plant species. [ABSTRACT FROM AUTHOR]

Luteolin is a natural flavonoid, which exists in many plants, including onions, broccoli, carrots, peppers, celery, olive oil, and mint. Luteolin is a dietary flavonoid with potent uric acid‐lowering and antioxidant bioactivities. To date, the mechanism by which luteolin alleviates hyperuricemia nephropathy (HN) still needs to be better defined. This study aims to evaluate the therapeutic efficacy of luteolin in a preclinical mouse model and in vitro. Luteolin was administered in the HN mice induced by the combination of potassium oxonate and hypoxanthine to evaluate the potential renoprotective effects in vivo. The NRK‐52E cells were stimulated with adenosine for in vitro evaluation. Hematoxylin and eosin staining, biochemical analysis, immunoblotting, immunofluorescence, and immunohistochemistry were performed for the histopathologic and mechanistic investigations. The results suggest that luteolin attenuated tubular dilation and epithelial atrophy in the renal tissue of HN mice. Further, luteolin improved biochemical indicators concerning renal functions and oxidative stress in vivo. Mechanistically, luteolin reduced the renal expressions of KIM‐1 and caspase‐3. Luteolin activated renal SIRT1/6 cascade and its downstream Nrf2‐mediated antioxidant pathway. Furthermore, luteolin elevated the renal expressions of ATP‐binding cassette subfamily G isoform 2 protein (ABCG2) and organic anion/cation transporters. In addition, livers of luteolin‐treated HN mice exhibited robust inhibition of xanthine oxidase. Together, our study shows that luteolin alleviates renal injury in the HN mice by activating urate excretion and Nrf2/HO‐1/NQO1 antioxidant pathways and inhibiting liver xanthine oxidase activity. Thus, luteolin may be a potential agent for the treatment of HN. [ABSTRACT FROM AUTHOR]

Background: Rose flowers contain active ingredients such as flavonoids and volatile oils and are acknowledged to be good natural resources owing to their anti-aging and antioxidant properties. In this study, we develop four new rose varieties (named Ever-rose) that are fragrant, pest resistant, and easy to grow. Subsequently, we evaluate the properties of Ever-rose and its potential for use in anti-aging products. Methods: The chemical composition of Ever-rose was determined using ultra-high-performance liquid chromatography triple time-of-flight mass spectrometry/mass spectrometry. The antioxidant activity of the Ever-rose extract was evaluated using various assays, including superoxide dismutase activity, 2,2-diphenyl-1-picrylhydrazyl radical-scavenging capacity, and xanthine oxidase activity. The variations in proteolytic matrix metalloproteinase-1 expression, collagen content after ultraviolet (UV) irradiation, and reactive-oxygen-species (ROS) levels after infrared A (IRA) treatment were evaluated. The variations in cell elasticity were assessed via atomic force microscopy. Results: The petal extracts of Ever-rose (named ER004(P), ER011(P), ER012(P), and ER015(P)) showed good antioxidant activity. They effectively inhibited UV irradiation-induced MMP-1 expression and IRA irradiation-induced increase in mitochondrial ROS levels. Additionally, they inhibited variations in cell shape and elasticity as aging progressed. In particular, ER011(P) demonstrated the best anti-aging and antioxidant effects. Conclusion: The newly developed Ever-rose showed excellent antioxidant and anti-aging effects. In particular, ER011(P) demonstrated the best properties owing to its high antioxidant content. Hence, it exhibits significant potential as a functional cosmetic ingredient. [ABSTRACT FROM AUTHOR]

Introduction: Gouty nephropathy (GN) arises from factors like excessive purine intake, metabolic disorders or abnormal synthesis, and uric acid hypersaturation in the blood, leading to urate crystal deposition in kidney tissue. DaiTongXiao (DTX) is a remedy used by the Dai people of China. It shows efficacy in lowering uric acid levels and exhibits anti-inflammatory and kidney-protective properties. Methods: A GN rat model was induced using adenine and potassium oxonate. Following DTX administration, various parameters were assessed in urine, serum, and kidney tissue. Western blot analysis evaluated TLR4/MyD88/NF-κB signaling proteins, while immunofluorescence examined NF-κB nuclear expression. Results: DTX treatment improved kidney morphology, increased body weight, and kidney index and enhanced urinary levels of blood urea nitrogen (Bun), 24-h urinary protein, uric acid (UA), and allantoin in GN rats, reducing UA, Bun, creatinine (Cre), cystatin C (CysC), serum amyloid A (SAA), α1-microglobulin (MG), and β2-MG in serum analysis. Renal tissue assessments showed decreased xanthine oxidase (XOD), hydroxyproline (Hyp), α-smooth muscle actin (α-SMA), and collage type Ⅳ (COL-Ⅳ). Kidney damage severity was notably reduced. DTX lowered serum inflammatory factors like interleukin (IL) -18, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), transforming growth factor-β1 (TGF-β1), and IL-1β in the rat serum, reducing chemokine monocyte chemoattractant protein-1 (MCP-1) and adhesion factor vascular cell adhesion molecule-1(VCAM-1). Western blotting demonstrated the downregulation of TLR4/MyD88/NF-κB pathway proteins, and immunofluorescence revealed reduced NF-κB expression in renal tissue. Discussion: DTX exhibits significant anti-GN effects by modulating TLR4/MyD88/NF-κB pathway protein expression, reducing inflammatory factor release, and inhibiting GN progression. [ABSTRACT FROM AUTHOR]

In this study, the Anoectochilus roxburghii (A. roxburghii) was studied for its chemical composition and biological activities. The first aim of this work was to isolate and purify compounds from A. roxburghii using Sephadex LH‐20 and HPLC. The identification of seven compounds was achieved, with 5,4′‐dihydroxy‐3,3′,7‐trimethoxy‐flavone and 5‐hydroxy‐3,4‐dimethyl‐5‐pentylfuran‐2(5H)‐one being isolated from A. roxburghii for the first time. The second aim was to describe its inhibition on the metabolism‐related enzyme activities in vitro. Further, 3,5‐dihydroxy‐7,3′,4′‐trimethoxyflavone and 5‐hydroxy‐3,4‐dimethyl‐5‐pentylfuran‐2(5H)‐one showed inhibitory activity on xanthine oxidase, while isorhamnetin‐3‐O‐rutinoside (IC50 = 87.45 μg/mL) may be potential inhibitors of α‐amylase. Molecular docking analysis revealed that isorhamnetin‐3‐O‐rutinoside exhibited the highest binding affinity towards PL. In addition to scientifically expanding the compound library of A. roxburghii, the discovery is also a vital reference for finding new insights in the field of medication research, especially as natural metabolism‐related enzyme inhibitors. [ABSTRACT FROM AUTHOR]

Diabetes affects 537 million adults globally, with 19.47 million cases in Indonesia. It arises from insufficient or ineffective insulin production, leading to complications like nephropathy. Due to the adverse effects of conventional medications, there is a growing need for safer alternatives. Functional foods and bioactive compounds show promise in managing diabetes. One such alternative is rice. Indonesia boasts a unique rice variety known as Pulu Mandoti, exclusively cultivated in the Enrekang District, Makassar, Indonesia. This delightful red rice variant offers numerous nutritional benefits. Unlike white rice, red rice is abundant in essential nutrients such as calcium, zinc, magnesium, protein, and fiber. The study focused on Pulu Mandoti, exploring its potential for antidiabetic and antioxidant activities using LC-MS analysis. Twelve (12) compounds were identified within the 1.23-14.41-min retention time range, with Compound 11 (2,2'-methylenebis(dibenzo[b,d]thiophene)) showing the strongest antioxidant potential compared to vitamin C. In molecular docking, Compound 11 exhibited the lowest binding affinity for both alpha-amylase and alpha-glucosidase (-10.5 and -8.7 kcal/mol, respectively), whereas acarbose displayed the highest binding affinity. For antioxidant analysis, Compounds 11 and 5 demonstrated the lowest binding affinities for NADPH oxidase and xanthine oxidoreductase, respectively, whereas vitamin C showed the highest. The coefficient values for drug properties similarity ranged from 0.40-0.76 for antidiabetic drugs, with Compound 5 displaying the highest coefficient value (0.76) and from 0.41-0.68 for antioxidants, with the highest value observed for antioxidant peptide A acetate. [ABSTRACT FROM AUTHOR]

Fabiana punensis S. C. Arroyo is a subshrub or shrub that is indigenous to the arid and semiarid region of northern Argentina and is known to possess several medicinal properties. The objective of this study was to optimize the extraction conditions so as to maximize the yield of bioactive total phenolic compound (TPC) and flavonoids (F) of F. punensis' aerial parts by using non-conventional extraction methods, namely ultrasound-assisted extraction, UAE, and microwave-assisted extraction, MAE, and to compare the biological activities and toxicity of optimized extracts vs. conventional extracts, i.e., those gained by maceration. Response Surface Methodology (RSM) was used to apply factorial designs to optimize the parameters of extraction: solid-to-liquid ratio, extraction time, ultrasound amplitude, and microwave power. The experimental values for TPC and F and antioxidant activity under the optimal extraction conditions were not significantly different from the predicted values, demonstrating the accuracy of the mathematical models. Similar HPLC-DAD patterns were found between conventional and UAE- and MAE-optimized extracts. The main constituents of the extracts correspond to phenolic compounds (flavonoids and phenolic acids) and apigenin was identified. All extracts showed high scavenger capacity on ABTS•+, O2•− and H2O2, enabling the inhibition of the pro-inflammatory enzymes xanthine oxidase (XO) and lipoxygenase (LOX). They also showed an antimutagenic effect in Salmonella Typhimurium assay and cytotoxic/anti-proliferative activity on human melanoma cells (SKMEL-28). Toxicological evaluation indicates its safety. The results of this work are important in the development of efficient and sustainable methods for obtaining bioactive compounds from F. punensis for the prevention of chronic degenerative diseases associated with oxidative stress, inflammation, and DNA damage. [ABSTRACT FROM AUTHOR]

In the present study, some hybrid compounds containing 1,2,3-triazole and naphthalene subunits 16(a–g) and 17(a–f) were synthesized and characterized by 1H, 13C-NMR, FT-IR, and HR-MS analyses. The in vitro inhibitor activities on the xanthine oxidase (XO) enzyme of all the target compounds were investigated and compared with allopurinol, which is one of the most common gout drugs and inhibits the XO. The activity results show that all the target compounds have potential XO inhibitor activities. The compounds showed IC50 values in the range of 0.825–2.254 μM on the XO. IC50 value of allopurinol on the XO was determined to be 1.475 μM. 16e and 17e compounds among them exhibited the best inhibitions compared to other compounds and allopurinol. Additionally, molecular docking studies were carried out on the 3D crystallographic structure of the XO to investigate possible interactions with the active site of the XO of all compounds. According to the docking results, all the target compounds showed that the best binding energies vary in the between − 9.71 kcal.mol−1 and − 11.43 kcal.mol−1. Finally, in silico ADME and toxicity properties of the compounds were investigated using the Swiss ADME, ProTox-II, and Osiris Property Explorer websites and it has been predicted that the target compounds have low toxicity profiles. Consequently, the compounds can be considered new promising inhibitors for the XO. [ABSTRACT FROM AUTHOR]

Plantaginis semen is the dried ripe seed of Plantago asiatica L. or Plantago depressa Willd., which has a long history in alleviating hyperuricemia (HUA) and chronic kidney diseases. While the major chemical ingredients and mechanism remained to be illustrated. Therefore, this work aimed to elucidate the chemicals and working mechanisms of PS for HUA. UPLC-QE-Orbitrap-MS was applied to identify the main components of PS in vitro and in vivo. RNA sequencing (RNA-seq) was conducted to explore the gene expression profile, and the genes involved were further confirmed by real-time quantitative PCR (RT-qPCR). A total of 39 components were identified from PS, and 13 of them were detected in the rat serum after treating the rat with PS. The kidney tissue injury and serum uric acid (UA), xanthine oxidase (XOD), and cytokine levels were reversed by PS. Meanwhile, renal urate anion transporter 1 (Urat1) and glucose transporter 9 (Glut9) levels were reversed with PS treatment. RNA-seq analysis showed that the PPAR signaling pathway; glycine, serine, and threonine metabolism signaling pathway; and fatty acid metabolism signaling pathway were significantly modified by PS treatment. Further, the gene expression of Slc7a8, Pck1, Mgll, and Bhmt were significantly elevated, and Fkbp5 was downregulated, consistent with RNA-seq results. The PPAR signaling pathway involved Pparα, Pparγ, Lpl, Plin5, Atgl, and Hsl were elevated by PS treatment. URAT1 and PPARα proteins levels were confirmed by Western blotting. In conclusion, this study elucidates the chemical profile and working mechanisms of PS for prevention and therapy of HUA and provides a promising traditional Chinese medicine agency for HUA prophylaxis. [ABSTRACT FROM AUTHOR]

Cordyceps militaris, well known for its therapeutic potential in managing type-2 diabetes through the inhibition of α-amylase and α-glucosidase enzymes, was the central focus of this research, which investigated the influence of various cultivation substrates on its enzymatic inhibitory properties and bioactive compound content. Previous studies have primarily focused on the general pharmacological benefits of C. militaris but have not thoroughly explored how different substrates affect its bioactive profile and enzyme inhibitory activities. This study aimed to evaluate the impact of substrate selection on the enzyme inhibition activities and the levels of bioactive compounds such as cordycepin and adenosine in C. militaris, demonstrating that substrate selection markedly affects both these enzymes' inhibition activities and bioactive compound levels. Particularly, C. militaris fruiting bodies grown on Brihaspa atrostigmella showed the highest concentrations of cordycepin (2.932 mg/g) and adenosine (1.062 mg/g). This substrate also exhibited the most potent α-glucosidase inhibition with an IC50 value of 336.4 ± 16.0 µg/mL and the most effective α-amylase inhibition with an IC50 value of 504.6 ± 4.2 µg/mL. Conversely, C. militaris cultivated on the solid residues of Gryllus bimaculatus displayed the strongest xanthine oxidase (XOD) inhibition, with the lowest IC50 value of 415.7 ± 11.2 µg/mL. These findings highlight the critical role of substrate choice in enhancing the medicinal properties of C. militaris, suggesting that optimized cultivation can enhance the bioactive properties for more effective natural therapies for diabetes and other metabolic disorders. This study not only extends the understanding of C. militaris' pharmacological potential but also illustrates its applicability in developing customized treatment options. [ABSTRACT FROM AUTHOR]

Background: We investigate whether Intensive uric acid (UA)-lowering therapy (ULT) provides increased renal protection compared with standard therapy in chronic kidney disease (CKD) patients. Methods: This was a multicenter randomized controlled trial. Only CKD patients with hyperuricemia were included in this study. The participants were randomly assigned to either the Intensive therapy group (target serum UA level ≥ 4.0 mg/dL and < 5.0 mg/dL) or the standard therapy group (serum UA level ≥ 6.0 mg/dL and < 7.0 mg/dL). ULT was performed using topiroxostat, a non-purine-type selective xanthine oxidase inhibitor. The primary endpoint was change in the logarithmic value of urine albumin to the creatinine ratio (ACR) between baseline and week 52 of the treatment. Results: Three hundred fifty-two patients were included in the full analysis set. In the Standard therapy group, mean serum UA was 8.23 mg/dL at baseline and 6.13 mg/dL at 52 weeks. In the Intensive therapy group, mean serum UA was 8.15 mg/dL at baseline and 5.25 mg/dL at 52 weeks. There was no significant difference in changes in log ACR at 52 weeks between the Intensive therapy and the Standard therapy groups. Conclusion: This study did not reveal the benefit of Intensive ULT to improve albuminuria levels. (UMIN000026741 and jRCTs051180146). [ABSTRACT FROM AUTHOR]

By inhibiting xanthine oxidase, subsequent inflammatory cytokine release and the resulting breakdown of the blood–retina barrier, allopurinol may limit the inflammation-driving diabetic macular edema (DME). We examined the relationship between allopurinol and DME among type 2 diabetic United States veterans using a retrospective cohort study. We used propensity score matching and Cox hazard models to estimate the risk of DME. Propensity score-matched Cox models revealed allopurinol was associated with a 24.6% reduction in the risk of DME (HR = 0.754; 95% CI = (0.684–0.831)). Allopurinol could reduce the risk of DME, one of the major causes of visual disturbance among diabetic patients. Further research into the effects of allopurinol on DME is warranted. [ABSTRACT FROM AUTHOR]

Background: The CRUCIAL trial (NCT04217421) is investigating the effect of postnatal and perioperative administration of allopurinol on postoperative brain injury in neonates with critical congenital heart disease (CCHD) undergoing cardiac surgery with cardiopulmonary bypass (CPB) shortly after birth. Objective: This study aimed to characterize the pharmacokinetics (PK) of allopurinol and oxypurinol during the preoperative, intraoperative, and postoperative phases in this population, and to evaluate target attainment of the current dosing strategy. Methods: Nonlinear mixed-effects modeling was used to develop population PK models in 14 neonates from the CRUCIAL trial who received up to five intravenous allopurinol administrations throughout the postnatal and perioperative periods. Target attainment was defined as achieving an allopurinol concentration >2 mg/L in at least two-thirds of the patients during the first 24 h after birth and between the start and 36 h after cardiac surgery with CPB. Results: A two-compartment model for allopurinol was connected to a one-compartment model for oxypurinol with an auto-inhibition effect on the conversion, which best described the PK. In a typical neonate weighing 3.5 kg who underwent cardiac surgery at a postnatal age (PNA) of 5.6 days, the clearance (CL) of allopurinol and oxypurinol at birth was 0.95 L/h (95% confidence interval 0.75–1.2) and 0.21 L/h (0.17–0.27), respectively, which subsequently increased with PNA to 2.97 L/h and 0.41 L/h, respectively, before CPB. During CPB, allopurinol and oxypurinol CL decreased to 1.38 L/h (0.9–1.87) and 0.12 L/h (0.05–0.22), respectively. Post-CPB, allopurinol CL increased to 2.21 L/h (1.74–2.83), while oxypurinol CL dropped to 0.05 L/h (0.01–0.1). Target attainment was 100%, 53.8%, and 100% at 24 h postnatally, 24 h after the start of CPB, and 36 h after the end of cardiac surgery, respectively. The combined concentrations of allopurinol and oxypurinol maintained ≥ 90% inhibition of xanthine oxidase (IC90XO) throughout the postnatal and perioperative period. Conclusions: The minimal target concentration of allopurinol was not achieved at every predefined time interval in the CRUCIAL trial; however, the dosing strategy used was deemed adequate, since it yielded concentrations well exceeding the IC90XO. The decreased CL of both compounds during CPB suggests influence of the hypothermia, hemofiltration, and the potential sequestration of allopurinol in the circuit. The reduced CL of oxypurinol after CPB is likely attributable to impaired kidney function. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a potentially fatal condition with no targeted treatment options. Although inhibiting xanthine oxidase (XO) in the treatment of AP has been studied in several experimental models and clinical trials, whether XO is a target of AP and what its the main mechanism of action is remains unclear. Here, we aimed to re-evaluate whether XO is a target aggravating AP other than merely generating reactive oxygen species that trigger AP. We first revealed that XO expression and enzyme activity were significantly elevated in the serum and pancreas of necrotizing AP models. We also found that allopurinol and febuxostat, as purine-like and non-purine XO inhibitors, respectively, exhibited protective effects against pancreatic acinar cell death in vitro and pancreatic damage in vivo at different doses and treatment time points. Moreover, we observed that conditional Xdh overexpression aggravated pancreatic necrosis and severity. Further mechanism analysis showed that XO inhibition restored the hypoxia-inducible factor 1-alpha (HIF-1 α)-regulated lactate dehydrogenase A (LDHA) and NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathways and reduced the enrichment of 13C 6 -glucose to 13C 3 -lactate. Lastly, we observed that clinical circulatory XO activity was significantly elevated in severe cases and correlated with C-reactive protein levels, while pancreatic XO and urate were also increased in severe AP patients. These results together indicated that proper inhibition of XO might be a promising therapeutic strategy for alleviating pancreatic necrosis and preventing progression of severe AP by downregulating HIF-1 α -mediated LDHA and NLRP3 signaling pathways. XO was enormously increased in necrotic murine models and severe patients of acute pancreatitis, pharmacological and genetic intervention of XO significantly affected disease severity via HIF-1 α -regulated LDHA and NLRP3 pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

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Hyperuricemia (HUA), or elevated uric acid in the blood, has become more prevalent in recent years. Polyphenols, which are known to have good inhibitory activity on xanthine oxidoreductase (XOR), are effective in uric acid reduction. In this review, we address the structure–activity relationship of flavonoids that inhibit XOR activity from two perspectives: the key residues of XOR and the structural properties of flavonoids. Flavonoids' inhibitory effect is enhanced by their hydroxyl, methoxy, and planar structures, whereas glycosylation dramatically reduces their activity. The flavonoid structure–activity relationship informed subsequent discussions of the changes that occur in polyphenols' XOR inhibitory activity during their extraction, processing, gastrointestinal digestion, absorption, and interactions. Furthermore, gastrointestinal digestion and heat treatment during processing can boost the inhibition of XOR. Polyphenols with comparable structures may have a synergistic effect, and their synergy with allopurinol thus provides a promising future research direction. [ABSTRACT FROM AUTHOR]

Eucalyptus citriodora Hook, also known as lemon-scented gum is a perennial plant that has been cultivated in North Sumatra for its essential oils and is being developed as a source medicinal compounds due to its bioactivities. While this plant has been extensively utilized for practical purposes in North Sumatra, empirical evidence regarding its antioxidant activity remains undisclosed, thereby piquing the interest of natural product chemists. To investigate the potential antioxidant activity of crude bioactive extracts from E. citriodora leaves, both in vitro and in silico studies were conducted. Crude extract was obtained by maceration of simplicia in methanol, followed by solvent-solvent extraction using hexane, and ethyl acetate. Antioxidant activity was determined using DPPH radical scavenging activity (in vitro). An in silico study was done using four protein targets namely; lipoxygenase, cytochrome P450 family 2 subfamily C member 9 (CYP2C9), NADPH-oxidase, and xanthine oxidase with curcumin and gallic acid as standard compounds. The highest yield was obtained from the hexane extract (54.3 g), followed by the methanol (42.5 g) and ethyl acetate extracts (11.6 g). The ethyl acetate extract of E. citriodora leaves showed the highest antioxidant activity (IC50 = 44.78 µg/mL), followed by the methanol (IC50 = 65.13 µg/mL), and hexane extracts (IC50 = 140.45 µg/mL). The best docking score expressed as high binding free energy was obtained on xanthine oxidase (ΔG = -6.7 kcal/mol) which was higher than the standard compound, gallic acid (ΔG = -6.5 kcal/mol). The high content of methyl gallate in the leaves of E. citriodora implies its prospect to be formulated into herbal drugs for the treatment hyperuricemia in the future. [ABSTRACT FROM AUTHOR]

Background: Orlistat (ORS) and metformin (MEF) are robustly used as well-established clinical drugs for the treatment for both obesity and the consequences of diabetes mellitus. Additionally, no study has been conducted to explore the consequence of the combination of both ORS and MEF on the kidneys of rats with obesity-induced renal injury (OBS). Objectives: Therefore, the objective of the current research was designed to explore the possible ameliorative effects of either ORS and/or MEF or their combination against obesity (OBS) induced experimental renal oxidative stress. Methods: Renal oxidative stress was investigated at redox histopathological and immunohistological points in the kidney tissues. Results: The levels of urea, uric acid, and creatinine increased with the obesity effect; in addition, the myeloperoxidase (MPO) and xanthine oxidase (XO) activators were elevated significantly with the induction of OBS. The levels of non-enzymatic antioxidants (glutathione and thiol) declined sharply in OBS rats as compared to the normal group. Conclusion: The data displayed that the combination of both ORS and MEF declined the obesity effects significantly by reducing the level of peroxidation (MDA), and enhancement intracellular antioxidant enzymes. These biochemical findings were supported by histopathology, immunohistochemistry, and Masson-Trichrome evaluation, which showed minor morphological changes in the kidneys of rats. [ABSTRACT FROM AUTHOR]

Introduction: Schinus terebinthifolia (ST) is a plant belonging to the cashew family Anacardiaceae, native to subtropical and tropical South America. ST is commonly called Brazil pepper and aroeira. Several reports have been made on the biological activities of ST, but studies on leaf extracts, especially lectins, have mainly been reported. Objectives: Our study analyzed the active compounds, antioxidant activities, xanthine oxidase inhibitory, elastase inhibitory, and tyrosinase inhibitory activities of S. terebinthifolia (ST) bark extract. Results: Hot water extracts showed the strongest electron donating ability (84.46%) and tyrosinase inhibitory activity (67.1%). Eighty percent ethanol extract showed the highest reducing power, total phenolic, xanthine oxidase (91.7%) and elastase inhibitory ability (85.44%). Catechin, α–amyrin, β–amyrone and 11-Oxo-.α-amyrin were identified through HPLC and GCMS analysis, while eighty percent extract contained the highest amount of catechin. Catechin, α–amyrin, and β–amyrone are considered to be the main xanthine oxidase inhibitors, while β–amyrone is considered to be the main inhibitor of xanthine oxidase and elastase. Conclusion: Through this study, we reported the basic information that S. terebinthifolia bark extract was used in folk medicine as an anti-inflammatory, anti-gout, and skin disease improvement material. S. terebinthifolia bark extract could be used as an anti-gout natural drug or cosmetic material. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is a metabolic disorder caused by abnormalities in purine metabolism that increase serum uric acid. Some traditional medicine remedies have been proven to cause hypouricemia by inhibiting xanthine oxidase. In Vietnam, some remedies that eliminate wind, cold, and dampness have been used to treat gouty arthritis, but there is still a lack of scientific evidence regarding the underlying biological mechanisms involved. This study aimed to assess the xanthine oxidase inhibitory activity in vitro and the hypouricemic effects of several Vietnamese remedies used to treat Bi syndrome in traditional medicine. Methods: The chosen remedies that met our criteria were successively extracted with 70% ethanol. A preliminary investigation of the chemical composition of the extracts was performed by common chemical reactions. The in vitro xanthine oxidase inhibitory activity of the extracts was investigated using the procedure of Noro et al (1983). Acute toxicology and hypouricemic effect of the remedy that showed the highest xanthine oxidase inhibitory activity were investigated in vivo using a potassium oxonate-induced hyperuricemic mouse model. Results: Five remedies that met the criteria were chosen. Phytochemical screening of all the extracts revealed the presence of flavonoids, saponins, alkaloids, tannins, and carbohydrates. The Bai nghiem phuong 2 extract did not show xanthine oxidase inhibitory activity whereas the Thang Tri Te Thap extract, which exhibited the highest inhibitory xanthine oxidase activity with an IC50 value of 48.33±0.41 µg/mL, was selected for the subsequent in vivo experiments. The Thang Tri Te Thap extract did not cause acute toxicity, with a Dmax of 31.67 g/kg. At doses of 1.5 g/kg and 3 g/kg, Thang Tri Te Thap significantly reduced the serum uric acid concentration by 59.84 ±5.79% and 65.01 ±12.73%, respectively (p < 0.05). Conclusions: Thang Tri Te Thap showed xanthine oxidase inhibitory activity in vitro and hypouricemic effects in vivo. [ABSTRACT FROM AUTHOR]

Abstract Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p

Abstract Xanthine oxidase (XO) is an enzyme that converts hypoxanthine into xanthine and xanthine into uric acid, which is then eliminated by the kidneys. Serum XO has been linked to diabetes, hypertension, liver dysfunction, and cardiovascular diseases. However, limited information exists on the relationship between serum XO activity and MetS. This study aimed to analyze the relationship between XO activity and metabolic syndrome (MetS) and its components in an adult population group in Bangladesh A total of 601 participants aged ≥18 years were included in the study. MetS was defined based on the criteria set by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Serum XO activity was measured using the enzyme-linked immunosorbent assay (ELISA), while other biochemical parameters were measured using colorimetric methods. The relationship between serum XO and MetS levels was determined through multivariate logistic regression analysis. Serum XO activity was found to be significantly higher in females (6.17 ± 3.77 U/L) as compared to males (4.00 ± 2.77 U/L) (p

In order to develop a purine-reducing functional yak yoghurt, Lactobacillus paracasei 259 and commercial starter was used as the fermentation strain in this experiment. The inoculation amount of yak yoghurt strain was optimized by single factor experiment, and the quality changes of yak yoghurt during post-ripening period and storage period were observed. Gas chromatography-mass spectrometry (GC-MS) was used to analyze the changes of flavor substances during post-ripening period and storage period, and the purine-lowering activity of yak yoghurt was determined by high performance liquid chromatography (HPLC). The results showed that the post-ripening time of yak yoghurt was 24 h, the sensory score was the best when the inoculation amount of Lactobacillus paracasei 259 was 5%, the number of viable bacteria was 3.1×108 CFU/mL, the acidity was 96°T, and the inhibition rate of xanthine oxidase (XOD) was 51.51%. Yak yogurt with 5% inoculum of Lactobacillus paracasei 259 had a viable bacterial count higher than 107 CFU/mL during 28 d of storage, and the acidity was lower than 105.4°T. With the increase of storage time, the pH and water holding capacity decreased gradually, and the sensory quality, hardness, cohesion, viscosity, consistency and XOD inhibitory activity increased first and then decreased. The main flavor substances in yak yogurt after ripening were alcohols, esters, ketones, aromatic heterocycles and sulfur compounds. The acids increased at storage period compared to the post-ripening period. The relative content and quantity of alcohols were the highest, which gave the yogurt a fruity, floral and sweet flavor. The degradation of inosine and guanosine in yak yogurt during the storage period firstly increased and then decreased, up to 84.6% and 86.5%, respectively. It can be seen that yak yogurt fermented by Lactobacillus paracasei 259 is of better quality, inhibits xanthine oxidase activity, effectively degrades inosine guanosine, and has good potential for application in the prevention and adjunctive treatment of hyperuricemia.

Context: Hyperuricemia is the cause of gout in the inflammatory joint condition. The xanthine oxidase enzyme is a therapeutic target for gout treatment because it plays a role in the generation of uric acid. Allopurinol is used to treat gout. It prevents the xanthine oxidase enzyme from producing as much uric acid. When selecting a medication, one must consider the various adverse effects of allopurinol. Phyllanthus emblica plants are among the medicinal plants that can be used as an alternative treatment for gout. Aims: To evaluate isolated compounds from the Phyllanthus emblica as antihyperuricemia candidates. Methods: The isolated compounds were characterized using High-Performance Liquid Chromatography Analysis and Thin Layer Chromatography-Densitometry. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cupric ion (CUPRAC) antioxidant capacity procedures were used to develop the antioxidant activity index. The ability to inhibit xanthine oxidase was determined using a spectrophotometer. Results: Compound 1 was indicated as rutin having antioxidant capacity with an antioxidant activity index (AAI) DPPH value of 7.89 ± 0.03 and AAI CUPRAC value of 15.83 ± 0.04 stronger than compound 2 (quercitrin) with an AAI DPPH value of 3.72 ± 0.01 and AAI CUPRAC 3.24 ± 0.03. The IC50 for quercitrin's inhibition of xanthine oxidase is 23.85 ± 2.04, which was higher than rutin’s IC50 value of 32.77 ± 4.49 µg/mL. Conclusions: Flavonol glycosides present in the ethanol extract of Phyllanthus emblica leaves gave potent xanthine oxidase inhibitory activity stronger than the extract. Quercitrin gave stronger xanthine oxidase inhibitory activity, but this compound has weaker antioxidant capacity compared to rutin.

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. [ABSTRACT FROM AUTHOR]

Diallyl trisulfide (DATS), a sulphur‐containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6‐trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS‐induced colitis. DATS treatment notably dampened the content of IL‐1β and IL‐18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL‐18 and IL‐1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF‐κB pathway activation by suppressing the expression of Trx‐1, thereby inhibiting NLRP3 inflammasome activation. Trx‐1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx‐1/ROS pathway. [ABSTRACT FROM AUTHOR]

An efficient acidic natural deep eutectic solvent (choline chloride-acetic acid, Chcl-AA) was screened out and subsequently combined with ultrasound treatment to recover seabuckthorn leaf phenolics (SLP), and the Plackett–Burman and Box-Behnken designs were used to optimize the process parameters. The optimal parameters were water content of NADES 30%, solvent to solid ratio 32 mL/g, extraction time 14 min, extraction temperature 40°C, ultrasonic power 400 W, and ultrasonic duty cycle 75%. The values of total phenolic content (TPC) and total flavonoid content (TFC) under these conditions were 99.65 ± 2.49 milligram gallic acid equivalent per gram of dry weight (mg GAE/g DW) and 52.02 ± 1.21 milligram rutin equivalent per gram of dry weight (mg RE/g DW), respectively. Twenty-five phenolics were initially identified from SLP by ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS), among which hydrolyzable tannins, isorhamnetin derivatives, and quercetin derivatives are the main constituents. The SLP extract was further evaluated as to its ability to inhibit metabolic enzymes, i.e., α-glucosidase, α-amylase, pancreatic lipase, cholesterol esterase, xanthine oxidase, and angiotensin-converting enzyme. SLP exhibited significant inhibition of α-glucosidase (IC50 = 3.31 μg/mL), pancreatic lipase (IC50 = 57.62 μg/mL), and angiotensin-converting enzyme (IC50 = 63.13 μg/mL). Additionally, the compounds extracted using Chcl-AA exhibited superior bioactivity when compared to those using conventional green solvents, i.e., ethanol and water. These results provide a valuable technical buttress for the efficient extraction of SLP and their further application and research in functional foods. [ABSTRACT FROM AUTHOR]

Musa balbisiana Colla plant belongs to the Musaceae family, which is well‐known for its nutritional and pharmacological properties. This study aimed to evaluate the anti‐xanthine oxidase, anti‐lipase, and anti‐tyrosinase activities of samples of corm, pseudostem, inflorescence, fruit, peel, and seed of M. balbisiana. The results show that seed performed the highest capacity in the inhibition of three investigated enzymes, with IC50 values of 290.25 μg/mL (anti‐tyrosinase), 141.51 μg/mL (anti‐xanthine oxidase), and 25.66 μg/mL (anti‐lipase). In addition, while fruit showed better performance in anti‐lipase inhibition (IC50: 32.72 μg/mL), corm pointed out higher capability on anti‐xanthine oxidase (IC50: 160.67 μg/mL) and anti‐tyrosinase (IC50: 334.43 μg/mL). The data show the high potential of the application of M. balbisiana parts in medical aesthetics, dietary supplements, or medicine. This is the first report to systematically present the biological activities of all parts of M. balbisiana grown in Vietnam. [ABSTRACT FROM AUTHOR]

Many microbes accumulate energy storage molecules such as triglycerides (TAG) and starch during nutrient limitation. In eukaryotic green algae grown under nitrogen-limiting conditions, triglyceride accumulation is coupled with chlorosis and growth arrest. In this study, we show that reactive oxygen species (ROS) actively accumulate during nitrogen limitation in the microalga Chlorella sorokiniana. Accumulation of ROS is mediated by the downregulation of genes encoding ROS-quenching enzymes, such as superoxide dismutases, catalase, peroxiredoxin, and glutathione peroxidase-like, and by the upregulation of enzymes involved in generating ROS, such as NADPH oxidase, xanthine oxidase, and amine oxidases. The expression of genes involved in ascorbate and glutathione metabolism is also affected under this condition. ROS accumulation contributes to the degradation of monogalactosyl diacylglycerol (MGDG) and thylakoid membrane remodeling, leading to chlorosis. Quenching ROS under nitrogen limitation reduces the degradation of MGDG and the accumulation of TAG. This work shows that ROS accumulation, membrane remodeling, and TAG accumulation under nitrogen limitation are intricately linked in the microalga C. sorokiniana. [ABSTRACT FROM AUTHOR]