Metabolomic profiling of Piper sarmentosum Roxb. Extracts reveals potent xanthine oxidase inhibition and anti-inflammatory effects.

Exploration, sequence optimization and inhibition mechanisms of xanthine oxidase inhibitory peptides from chicken hemoglobin.

Accelerated de novo design of xanthine oxidase-inhibitory peptides via physics-informed computational approaches.

Natural drug-derived carbon dots as a novel oral dosing strategy for gouty arthritis.

Febuxostat alleviates gout-associated hyperuricemia and inflammation by downregulating IL1A to modulate TLR2/TLR4/NF-κB signaling pathway.

A triple-mode sensing platform for xanthine oxidase activity monitoring and inhibitor screening based on fluorescent trimetal-organic framework with efficient peroxidase-mimetic activity.

Clinically, hyperuricaemia is caused by increased uric acid synthesis catalysed by the enzyme xanthine oxidoreductase. This enzyme exists in two forms: xanthine dehydrogenase, which oxidises hypoxanthine to xanthine, and xanthine oxidase, which oxidises xanthine to uric acid. Agarwood leaves (Aquilaria malaccensis Lam.) possess antihyperuricemic activity. The flavonoid compounds contained in agarwood leaves are thought to inhibit the production of this enzyme. This study aimed to assess the inhibitory activity of agarwood leaf extracts and fractions against xanthine oxidase and to identify the active compounds in the extracts and fractions. Agarwood leaves were macerated with 96% ethanol and fractionated by liquid-liquid extraction with n-hexane, ethyl acetate, and water. The ethanol extract and fractions obtained were tested for their inhibitory activity against xanthine oxidase in vitro using a spectrophotometer at 295 nm. To determine the functional groups and active compounds, the extracts were analysed by Fourier transform infrared spectroscopy (FTIR), and the ethyl acetate fractions were analysed by liquid chromatography-mass spectrometry (LC-MS) and FTIR. The results showed that the percentage of xanthine oxidase inhibition was 92.05%, 47.88%, 91.17%, and 57.60% for the ethanol extract, n-hexane fraction, ethyl acetate fraction, and aqueous fraction, respectively. FTIR analysis showed the presence of O–H functional groups, while LC-MS analysis showed flavonoids as the main constituents. It can be concluded that the ethyl acetate fraction contains flavonoids that can inhibit the xanthine oxidase enzyme.

Caulerpa racemosa harbors a rich reservoir of bioactive peptides derived from RuBisCO, a photosynthetic enzyme with promising therapeutic potential. This study aimed to systematically identify and characterize bioactive peptides from C. racemosa RuBisCO using a multi-step in silico pipeline. Simulated proteolysis using 33 enzymes predicted peptides with 35 different biological activities using BIOPEP-UWM. In addition to traditional database screening, further computational filtering was conducted using physicochemical profiling (ExPASy ProtParam), bioactivity prediction (PeptideRanker), toxicity and allergenicity evaluation (ToxinPred, AllergenFP), and structure-based molecular docking against relevant therapeutic targets—angiotensin-I converting enzyme (ACE, PDB: 1O8A) and xanthine oxidase (XO, PDB: 3NRZ). Four peptides with high predicted bioactivity scores (>0.75) showed strong binding affinity (−169.00 to −252.29 kcal/mol) and favorable confidence scores, suggesting their possible use as dual-action therapeutic agents—with both antihypertensive and antioxidant effects. This integrative in silico approach demonstrates the therapeutic relevance of C. racemosa peptides and provides a framework for peptide prioritization prior to experimental validation.

The study examines the pathogenetic mechanisms of fetal distress in pregnant women with chronic polyhydramnios, in light of current scientific evidence. The purpose of the study to evaluate the informative value of vascular endothelial growth factor (VEGF) concentrations and oxidative stress markers as potential diagnostic and prognostic indicators of fetal distress in pregnant women with chronic polyhydramnios, and to determine their strategic relevance for the early identification and prevention of perinatal complications under conditions of prolonged exposure to exogenous and psycho-emotional stressors. Materials and methods. Thirty women with physiologic pregnancy and 90 pregnant women with chronic polyhydramnios were enrolled. In blood serum obtained following standard collection and centrifugation procedures, VEGF concentrations were measured by enzyme-linked immunosorbent assay (ELISA); superoxide dismutase and xanthine oxidase activities, as well as malondialdehyde (MDA) and protein carbonyl group concentrations, were determined using standard spectrophotometric methods. Statistical analysis was performed using the Student t test and the Mann–Whitney U test, along with Pearson and Spearman correlation analysis; differences were considered statistically significant at p < 0.05. The research was conducted in accordance with the fundamental principles of bioethics. Statistical analyses were carried out using standard procedures implemented in Microsoft Excel and Statistica SPSS version 10.0 for Windows (IBM Corp., Armonk, NY, USA). Data are presented as the arithmetic mean ± standard error of the mean (M ± m). The study was performed as part of the the strategic research program of Vinnitsa National Pirogov Memorial Medical University, “Establishing modern aspects of preserving and restoring the health of women of different age groups” (State Registration Number: 01212U109714; January 2020 – December 2024). Results. Chronic polyhydramnios was associated with a significant 20.2% reduction in VEGF concentration and an 18.4% decrease in superoxide dismutase (SOD) activity, occurring concomitantly with a 29.7% increase in xanthine oxidase activity and accumulation of lipid peroxidation products. The progression to fetal distress was linked to a further deterioration of this imbalance: VEGF levels decreased by 26.4% compared with those in physiologic pregnancy, whereas MDA concentration increased by approximately 1.5-fold. Conclusions. The molecular basis of fetal distress in the setting of polyhydramnios involves a combination of angiogenic insufficiency and uncontrolled oxidative stress, which is potentiated by exogenous factors, including infection and psychoemotional stress.

Hyperuricemia is a metabolic disorder associated with an increased risk of gout, chronic kidney disease (CKD), and cardiovascular disease (CVD). The management of hyperuricemia in conditions where urate deposition has already occurred primarily relies on xanthine oxidase inhibitors (XOIs), such as allopurinol and Febuxostat. Febuxostat, a non-purine selective XOI, has demonstrated superior urate-lowering efficacy, particularly in patients with renal impairment. This review provides an in-depth analysis of Febuxostat's pharmacological properties, clinical efficacy, and safety profile, with a focus on cardiovascular and nephroprotective effects.

Xanthine oxidase inhibitors (XOis) are commonly used to treat gout and hyperuricemia. Beyond urate-lowering effects, XOis may influence cardiovascular outcomes via oxidative stress pathways. Prior evidence, including post hoc analyses of the CARES trial, suggests increased mortality after XOi discontinuation, raising concern for a potential "withdrawal syndrome." However, evidence from real-world outpatient populations is limited. This study aims to evaluate whether the recent discontinuation of XOi therapy is associated with an increased risk of acute cardiovascular events in patients with gout. We conducted a retrospective cohort study using the Merative MarketScan database. Adults with gout initiating allopurinol or febuxostat were included. Discontinuation was defined as no XOi supply in the prior 90days during the 121- to 180-day window post-initiation. The primary outcome was hospitalization or outpatient diagnosis of acute myocardial infarction or ischemic stroke. Cox proportional hazards models with stabilized inverse probability weights were used to estimate hazard ratios (HRs), adjusting for demographic and clinical covariates. Among 508,872 patients initiating XOi therapy, 23.6% discontinued therapy within the first 121- to 180-day post-initiation timeframe. Discontinuers were younger with fewer comorbidities at baseline. After weighting, groups were well balanced. XOi discontinuation was associated with a modest but statistically significant increased risk of acute cardiovascular events (HR, 1.05; 95% CI, 1.01-1.09; p = 0.019). The magnitude of the effect increases among patients with preexisting hypertension diagnoses (HR, 1.13; 95% CI, 1.03-1.23; p = 0.006). In this large real-world cohort, early discontinuation of XOi therapy was linked to a small but significant elevation in cardiovascular risk. These findings support prior signals of potential harm from XOi withdrawal, particularly among patients with cardiovascular disease, and highlight the importance of sustained therapy adherence. Key Points • Xanthine oxidase inhibitor (XOi) discontinuation was associated with a modest but significant increase in acute cardiovascular events in a large national cohort of patients with gout. • Even early discontinuation after XOi initiation may increase cardiovascular risk, underscoring the importance of treatment persistence. • Adherence to XOi therapy may be an important factor in reducing cardiovascular risk among gout patients.

The rhizome of Homalomena occulta has been widely used in traditional medicine to strengthen tendons and bones, alleviating inflammation, and also relieving pain associated with rheumatoid arthritis and osteoarthritis in the aged individuals. This study aimed to investigate the xanthine oxidase inhibitory activity (in vitro) and to evaluate its anti-inflammatory effect on the Freund's Complete Adjuvant (FCA) - induced paw edema mouse model, as well as its uric acid-lowering effect in a potassium oxonate–induced chronic hyperuricemia model in male Swiss albino mice of the 45% ethanol extract from H. occulta rhizomes (HO). Although HO showed xanthine oxidase inhibitory activity (IC50 = 177.34 μg/mL), its effect was weaker than that of allopurinol. This study demonstrated that HO at doses of 0.412 g/kg and 0.824 g/kg (equivalent to 2.5 g/kg and 5 g/kg of raw material, respectively) significantly reduced paw edema in the chronic inflammation model and decreased plasma uric acid levels compared with the disease model group. The effects were comparable to those of standard therapeutic agents such as diclofenac and allopurinol, respectively. These findings support the potential development of H. occulta rhizome extract as a promising herbal preparation for the treatment of chronic inflammatory conditions and hyperuricemia.

Urolithin A is an anti-aging and anti-inflammatory gut bacterial metabolite derived from ellagic acid (EA), a polyphenol abundant in berries and nuts. The conversion of EA to urolithin A involves multiple chemically challenging phenol dehydroxylation steps that produce urolithins with varying bioactivities. Despite their biological and chemical significance, the bacterial enzymes responsible for urolithin production remain largely unidentified. Here, we use differential gene expression analysis, anaerobic protein production, and enzyme assays to identify members of two distinct molybdenum enzyme families (the DMSO reductase family and the xanthine oxidase family) capable of regioselective dehydroxylation and urolithin generation. These two enzyme families have distinct substrate requirements, suggesting they employ different catalytic mechanisms for phenol dehydroxylation. Multiomics analysis of a human cohort uncovers decreased levels of urolithin A and genes encoding urolithin A-producing enzymes in patients with inflammatory bowel disease (IBD), implying reduced health effects of EA consumption in this setting. Together, this study elucidates the molecular basis of urolithin production, expands the known enzymatic repertoire of the human gut microbiome, and suggests a potential link between gut bacterial urolithin production and reduced host inflammation.

Coleus strobilifer, the dried rhizome and root of Coleus strobilifer (Roxb.) A.J. Paton, is widely used for dampness-detoxification and detumescence in Chinese folklore. This study marks the first comprehensive investigation into the chemical composition of the whole herb of C. strobilifer, leading to the isolation and identification of two new abietane diterpenes, 10R-carnosuain (1) and 10R-coleon U-3-one (2), along with 34 known compounds (3–36) isolated from C. strobilifer for the first time. Their structures were unambiguously elucidated by analyses of NMR, HRESIMS, IR, CD, and single-crystal X-ray diffraction data, and comparison with the literature. All the isolated compounds were screened for their xanthine oxidase (XO) inhibitory activity. Among them, apigenin (8), luteolin (9), and esculetin (29) showed moderate XO inhibitory activity with IC50 values of 0.034 ± 0.004, 0.067 ± 0.005, and 0.284 ± 0.01 mM, respectively.

DNA damage resulting from oxidative stress plays a major role in cancer formation. Despite DNA damage, the inability of cells to enter apoptosis due to irregularities in apoptotic protein levels and the induction of their proliferation as a result of the increase in polyamine levels causes the development and progression of cancer. The anticancer effects of Rhus coriaria L. extracts on lung cancer, colon cancer and fibroblast cell lines were determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide). Total antioxidant status (TAS) was analyzed with a commercial kit. The expression levels of genes related to apoptosis and the polyamine pathway in lung and colon cancer cell lines were analyzed by a Real-time Polymerase Chain Reaction (RT-PCR) device. Rhus coriaria L. extracts were found to have anticancer effects selectively on A549 and HT-29 cancer lines. It has also been shown that Rhus coriaria L. extracts have strong antioxidant capacity and can inhibit the Xanthine Oxidase (XO) enzyme in a dose-dependent manner. Afterwards, the interactions of the molecules in extracts of Rhus coriaria L. against various proteins such as colon cancer protein (PDB ID: 3DTC and 4UYA) lung cancer protein (PDB ID: 4ZXT and 5ZMA) were examined, and their activities were compared. MM/GBSA methods of the molecule with the best docking score are calculated as binding free energy.

IntroductionAlthough Phellinus igniarius has been shown to treat hyperuricemia (HUA) and gout, a self-inflammatory disease caused by purine metabolism disorders, the underlying mechanisms remain unclear. Polysaccharides are among the main components of P. igniarius with anti-inflammatory and immunoregulatory properties.MethodsHere, we examined the therapeutic effects of polysaccharide SH-P-1-1 isolated from P. igniarius on HUA and gout, and explored the underlying mechanism, focusing on gut microbiota and metabolite regulation.ResultsSH-P-1-1 significantly decreased uric acid and creatinine levels, reduced xanthine oxidase and adenosine deaminase activities, alleviated kidney damage, and reduced urate deposition in joints in model rats. It increased the abundance of Blautia and Muribaculaceae but reduced that of the Lachnospiraceae_NK4A136_group, Lactobacillus, and Turicibacter. SH-P-1-1 also significantly modulated the metabolic profile and was closely related to some metabolic pathways, such as tryptophan metabolism, relevant to HUA and gout. The beneficial activities of SH-P-1-1 correlated with gut microbiota composition and differential metabolites, including short-chain fatty acids.DiscussionOverall, this study demonstrates the potential of SH-P-1-1 as a natural supplement for preventing and managing HUA and gout.

Free radicals are key contributors to several diseases, including cancer, inflammation, pain, and neurodegenerative disorders such as Alzheimer's disease. Due to the limitations and adverse effects of synthetic antioxidants, naturally occurring phytochemicals offer safer, more sustainable alternatives. This study investigates the antioxidant potential of twigs of Combretum molle R. Br. ex G. Don through integrated experimental and computational approaches. Compounds were isolated using chromatographic methods, and their structures established by 1D- and 2D-NMR, HR-ESI-MS, and comparison with reported data. Antioxidant activity was assessed through DPPH radical scavenging and FRAP assays, while molecular docking against xanthine oxidase (PDB: 1FIQ) explored possible mechanisms beyond direct radical scavenging. A new macrocyclic bisbibenzyl derivative, combrebisbibenzyl A (1), was identified along with corosolic acid (2), maslinic acid (3), a mixture of asiatic acid (4) and arjunolic acid (5), combregenin (6), and β-sitosterol glucoside (7). The MeOH extract and EtOAc fraction showed notable DPPH scavenging activity (IC₅₀ = 170.21 and 197.41 μg/mL) and strong reducing power (65.04 ± 1.07 and 67.42 ± 0.82 mM Vit C/g). Among the isolated compounds, combrebisbibenzyl A (1) displayed the strongest radical scavenging effect (IC₅₀ = 175.64 μg/mL) and high reducing capacity (57.46 ± 0.42 mM Vit C/g). Docking indicated favorable interactions for all compounds, with combrebisbibenzyl A (1) showing the highest affinity (-9.1 kcal/mol), outperforming salicylate (-7.7 kcal/mol). These findings support the traditional use of C. molle and highlight combrebisbibenzyl A (1) as a promising natural antioxidant with multi-mechanistic potential.

The aim was to develop chemical composition of raspberry shoot extract using theoretical and experimental methods based on ionization theory. The quantification of phenolic compounds was accomplished through HPLC, the content of organic and phenolcarboxylic acids was determined by GC, molecular docking of the cyclooxygenase-2 (COX-2), phospholipase A2. nuclear factor kB (NF-kB), 5-lypoxygenase (5-LOX), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, myeloperoxidase, xanthine oxydase enzymes was carried out using the AutoDockTools 1.5.6 software, the anti-inflammatory activity was studied with the carrageenan edema method. The 11 compounds were identified by the HPLC and 36 compounds were detected by GC. The epicatechin (882.00 mg/100 g), (+)-catechin (480.00 mg/100 g), ellagic acid and its derivatives (459.00 mg/100 g), citric acid (49.21 mg/100 g), vanillic acid (2.59 mg/100 g) and levulinic acid (64.67 mg/100 g) were dominated in the obtained extract of raspberry shoots. The free energy of (+)-catechin-anion, epicatechin-anion was higher than (+)-catechin and epicatechin for the active sites of COX-2. phospholipase A2. NF-kB, 5-LOX, NADPH oxidase, myeloperoxidase, xanthine oxidase enzymes. Treatment with arginine-ionized raspberry shoot extract at a dose of 6.5 and 13.0 mg/kg showed a significant reduction of paw edema after 1. 2. 3 and 4 hours by 89.6 and 53.3, 49.4 and 53.3, 40.6 and 45.7, 45.9 and 45.2% compared with the control group, respectively. It has been established that (+)-catechin anion and epicatechin anion have a higher level of affinity than non-ionized (+)-catechin and epicatechin for the active centers of enzymes. The ionized extract showed a significantly higher anti-inflammatory effect than the non-ionized extract. In addition, there was a matching of experimental and theoretical doses in the study of anti-inflammatory activity.

According to the world health organization (WHO), gout and hyperuricemia have been affecting over 41 million people worldwide, due to uric acid crystal accumulation in joints which causes severe pain and inflammation. Xanthine oxidase (XO) is the key enzyme in uric acid synthesis and a major therapeutic target. Although febuxostat effectively inhibits XO, its side effects and inconsistent efficacy necessitate safer alternatives. This study employed molecular docking using AutoDock 4.2.6, Chimera 1.17.2, and SwissADME to evaluate binding affinity and pharmacokinetic properties of potential ligands such as ulodesine, arhalofenate, and verinurad. Results revealed that ligands with lower binding energies and favorable pharmacokinetic profiles may serve as promising XO inhibitors. The findings highlight ulodesine and related compounds as potential safer and more effective alternatives to febuxostat for gout treatment.

Cancer is a leading cause of mortality worldwide, which has led to further research in developing more effective therapeutics. We synthesized amphipathic cationic peptides incorporating 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic acid) into their backbones to explore their potential anticancer properties. The MCF-7 cell line was selected to evaluate cell viability, inhibition percentage, and cytotoxic effects of the synthesized decapeptides. The results suggested DEC-1 (IC50 = 3.38 µM) to be the most potent candidate, showcasing antiproliferative activity similar to the standard drug tamoxifen (IC50 = 2.68 µM). Structural characterization of the peptides confirmed the successful incorporation of Tic into the peptide backbones. The peptides were docked with xanthine oxidase (PDB ID: 2CKJ) and Nrf2 (Nuclear factor erythroid 2-related factor 2) inhibitor protein Keap-1 (PDB ID: 7Q6S), revealing strong binding interactions, particularly for DEC-1, having a binding score of nearly -8.864 kcal/mol-which is stronger than its reference ligand with Keap-1 protein-suggesting possible inhibitory roles in cancer cell proliferation and oxidative stress regulation. These promising findings indicate that the potent molecule DEC-1 can be taken for further studies and might lead to a potential therapeutic agent for cancer treatment.