A new isoflavone-quinone, placovinone E (1), and a new natural isoflavone, placovinone F (2), together with four known isoflavones (3–6), were isolated from the leaves of P. vietnamense. The chemical structures of all isolated compounds were elucidated using spectroscopic techniques (NMR and HRESIMS) and confirmed by comparison with literature data. All isolated compounds were evaluated for their α-glucosidase and xanthine oxidase inhibitory activities. Among them, compound 1 exhibited the strongest α-glucosidase inhibition (IC50 21.6 ± 1.04 µM), which was markedly more potent than the positive control, acarbose (IC50 156.2 ± 5.43 µM). In addition, compound 1 showed the highest xanthine oxidase inhibitory activity (IC50 32.8 ± 0.08 µM), although it remained considerably less potent than the positive control, allopurinol (IC50 2.45 ± 0.01 µM).

Hyperuricemia (HUA) has become a worldwide metabolic disease, which can lead to acute gout attacks, renal dysfunction, uric acid (UA) urolithiasis, and cardiovascular damage. Probiotics, known for their cost-effectiveness, minimal toxic side effects, and high safety profile, have shown potential in alleviating HUA. In the present study, the beneficial function of Lactobacillus plantarum TY-S8 on HUA and related mechanisms were comprehensively investigated by constructing a mice model of hyperuricaemia, combined with the use of microbiomics and metabolomics. Our results demonstrated that L. plantarum TY-S8 markedly lowered serum UA (SUA) concentrations by 22.41%, suppressed xanthine oxidase (XOD) activity and modulated the level of key transporters, including GLUT9, ABCG2, and NTP1. Furthermore, the pathological damage in the liver, kidney and colon of hyperuricemic mice was alleviated by the probiotics. Meanwhile, the strain upregulated the levels of occludin, a key tight junction protein, and promoted the synthesis of short-chain fatty acids (SCFAs), with a notable increase in butyric acid. Microbiome sequencing and analysis revealed that L. plantarum TY-S8 significantly increased the proportions of Lactobacillus johnsonii and Limosilactobacillus reuteri. Additionally, metabolomic analysis of fecal and blood samples indicated that the differential metabolites among the three groups were primarily indole derivatives, such as indole-3-acetic acid (IAA), indole-3-lactic acid (ILA), and indole-3-acetaldehyde (IAAld), which are involved in the tryptophan metabolism pathway. Notably, there is a clear correlation between the key bacterial strains and these differential metabolites. At last, fecal microbiota transplantation (FMT) was performed to confirm that the ameliorative effect of L. plantarum TY-S8 on the hyperuricemic mice is primarily mediated by the regulation of gut microbiota and tryptophan metabolites. In conclusion, L. plantarum TY-S8 exerts probiotic effects on hyperuricemic mice through multiple pathways. In particular, it alleviates intestinal inflammation by regulating tryptophan metabolism, thereby effectively promoting uric acid metabolism, which highlights its potential value in the intervention of HUA.

Searching for potential xanthine oxidase inhibitors from Vietnamese herb plants via computational studies.

Oxidative Stress-Induced mechanisms in neurodegeneration and Eryptosis: Implications for neurological and systemic disorders.

Challenges in chiral discrimination at the H-2 and H-10 positions of dihydrobenzofuran from Artemisiacapillaris.

Accumulation and transformation of C6, C9 and C12 phenols from the peel, leaves and branches of Nephelium lappaceum L.

Impact of the menstrual cycle on oxidative stress, inflammation and iron status at high altitude.

In this study, we investigated the dynamic changes in XOD inhibition and antioxidant activity during solid-state fermentation of Maclura tricuspidata leaves mediated by Ganoderma lucidum. XOD inhibitory activity was measured using an HPLC-based uric acid assay, while antioxidant capacity was evaluated through DPPH, ABTS, and FRAP assays, along with total phenolic and flavonoid content analyses. Notably, XOD inhibitory activity exhibited a linear decline from 83.47 ± 1.35% to 32.50 ± 0.60% over 72 h of fermentation. In contrast, total phenolic content, total flavonoid content, and antioxidant activities showed non-linear, time-dependent variations rather than consistent increases or decreases, suggesting complex biochemical changes. These results indicate that G. lucidum-driven solid-state fermentation triggers dynamic biotransformations in MT leaves. The observed decoupling between antioxidant capacity and XOD inhibition highlights the functional complexity of fermented MT products and suggests potential applications in managing hyperuricemia and conditions related to oxidative stress.

Background This study aims to evaluate the efficacy of Guiling Prescription (GP)—a medicinal food homologous formula—in hyperuricemic rats, its effects on uric acid excretion and renal function, and to clarify the metabolic mechanisms involved in GP's alleviation of hyperuricemia. Methods Sprague-Dawley (SD) rats of hyperuricemia was established using potassium oxonate (200 mg/kg, PO) and adenine (100 mg/kg) to assess the therapeutic effects of Guiling Prescription (GP). We measured body weight, serum levels of uric acid and creatinine, as well as xanthine oxidase (XOD) and adenosine deaminase (ADA) activity, alongside histopathological parameters. Serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were determined using ELISA kits. The expression of renal uric acid transporters was evaluated through Western blotting. Network pharmacology was utilized to predict the key drug-disease targets, and a non-targeted metabolomic assay was applied to identify the key metabolites and metabolic pathways, and validated these targets through molecular docking and western blot analyses. Results GP showed an improvement effect on hyperuricemia model rats, with decreased levels of serum uric acid (UA), serum urea nitrogen, and creatinine, and serum ALT, AST. Furthermore, H&E staining results showed to improve renal injury in the hyperuricemic rat, and serum interleukin-6 and tumor necrosis factor-αwere improve the body's inflammatory response after administration of GP. In addition, GP could regulate multiple serum metabolic pathways such as arachidonic acid metabolism, pyrimidine metabolism, purine metabolism, citric acid cycle. On one side, GP decreased the synthesis of uric acid by inhibiting hepatic xanthine oxidase activities and adenosine deaminase activity. On the other side, GP increased the excretion of uric acid with the upregulation of UA excretion genes ABCG2, OAT1, and OAT3 and downregulation of UA resorption genes URAT1 and GLUT9. Conclusion GP orchestrates uric acid metabolism through multi-target and multi-pathway regulation, highlighting its potential not only as a novel therapeutic strategy but also as a promising dietary supplement for the management of hyperuricemia.

Heat-inactivated Akkermansia muciniphila AKK PROBIO attenuates hyperuricemia via integrated modulation of uric acid metabolism, TLR4/NF-κB/NLRP3 pathway, and gut microbiota.

Valproic acid (VPA) is a short-chain fatty acid used to treat disorders of the brain. When VPA is used for long term, it causes damage, particularly through the formation of free radicals. The lungs are among the organs most affected by long-term VPA treatment. Some antioxidant substances are used to prevent damage caused by free radicals. One of these substances is alpha-lipoic acid (ALA), which occurs naturally. In our study, the protective effect of ALA against VPA-induced lung injury was investigated. In this study, female Sprague-Dawley rats were divided into four groups. The 1st group served as the control (1 mL olive oil); the 2nd group received ALA (50 mg/kg/day) for 15 days; the 3rd group received VPA (0.5 g/kg/day) for 15 days; and the 4th group received both VPA and ALA at the same doses and for the same duration. ALA and VPA were dissolved in olive oil. On day 16, all groups were euthanized under anesthesia. The lung tissues were collected and homogenized. In the prepared supernatants, the levels of reduced glutathione and total antioxidant status, and the activities of glutathione reductase, glutathione peroxidase, catalase, paraoxonase, carbonic anhydrase, aryl esterase, and superoxide dismutase were decreased in the VPA group, while sialic acid, lipid peroxidation, reactive oxygen species, total oxidant, oxidative stress index, hydroxyproline, glycoprotein levels, and xanthine oxidase activities were increased in the VPA group. These values were reversed in ALA when VPA was administered. As a result, it may be concluded that ALA exerts protective effects against VPA-induced lung damage.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a peril to public health. Xanthine oxidoreductase (XOR) is implicated in oxidative stress and lipid metabolism, which constitute the pathological basis of MASLD. As a specific XOR inhibitor, febuxostat therefore exhibits considerable potential for mitigating MASLD. However, the efficacy and underlying mechanisms of febuxostat in this context remain to be elucidated. Against this background, the present study aimed to observe the effect of febuxostat on the physiological changes of male MASLD rats and explore the related mechanisms. All rats were assigned to three groups: control, high-fat diet (HF), and high-fat diet with febuxostat (HF + F). After euthanasia, biosamples were immediately harvested to conduct an extensive suite of experiments, encompassing histological examination, assessment of biochemical and oxidative stress markers, serum non-targeted metabolomics, and Western blot analysis. Histological examination showed marked reductions in hepatic lipid accumulation and hepatocellular degeneration in the HF + F group relative to the HF group. Consistently, compared to the HF group, the HF + F group showed significant reductions in the elevated levels of plasma/hepatic lipids, and plasma oxidative stress markers (p < 0.05). Serum metabolomics revealed distinct metabolic profiles among groups, with 51 differential metabolites between HF + F and HF groups, with pathways such as taurine and hypotaurine metabolism and starch and sucrose metabolism being significantly altered (p < 0.05). Western blot analysis showed reduced p-JNK and increased NRF2 and HO-1 expression in the HF + F group (p < 0.05). In summary, we found that inhibiting XOR with febuxostat improved hepatic steatosis, serum metabolic dysregulation and systemic oxidative stress status, and it accompanied by JNK/NRF2/HO-1 pathway key molecule protein alterations in male MASLD rats.

Reactive oxygen species (ROS)-induced aberrant oncogenic signalling has been proposed to mediate the progression and development of pleural mesothelioma (PM). In this study, we demonstrate how ROS promote oncogenic signalling, especially in the context of cell migration and immune evasion via YB-1 phosphorylation in mesothelial and PM cell models. Xanthine (X)- and xanthine oxidase (XO)-generated ROS exposure led to increased migration and a more elongated cell shape in mesothelial and PM cells in live-cell videomicroscopy analyses. These effects were associated with the enhanced phosphorylation of ERK, AKT, and YB-1 and the elevated gene expression of PD-L1 and PD-L2, which were analysed with immunoblotting and quantitative real-time RT-PCR, respectively. The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

Syzygium cumini (Jamun) is recognized for its rich bioactive profile and potential therapeutic applications, particularly for conditions like hyperuricemia and oxidative stress. This study employs a comprehensive approach to identify and evaluate the pharmacokinetic properties, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) characteristics, and toxicological profiles of 13 phytochemicals from S. cumini bark. Target prediction linked several of these compounds to hyperuricemia-related enzyme inhibition. ADMET analysis, along with Lipinski’s rule of five, confirmed their drug-likeness and bioavailability, identifying candidates such as 11-O-galloylbergenin, Betulinic acid, and Gallic acid as promising due to their ability to permeate biological barriers and interact with P-glycoprotein. Molecular docking highlighted notable binding affinities for three key enzymes involved in hyperuricemia: Xanthine oxidase (3NRZ), Hypoxanthine-Guanine Phosphoribosyltransferase (HGPR) (3GGC)), and Adenosine deaminase(1O5R). Specifically, 11-O-galloylbergenin, Ellagitannin, and Canthaxanthin exhibited strong interactions, with binding energies of -10.8 kcal/mol, -9.7 kcal/mol, and -11.1 kcal/mol, respectively. These results suggest their potential as enzyme inhibitors, supporting their development as natural treatments for uric acid-related conditions. Toxicity assessments confirmed that most compounds possess safe profiles, underscoring S. cumini’s value in producing safe, plant-based therapeutics. This work provides a foundation for future research on S. cumini’s bioactive compounds, encouraging further in vivo studies to validate their efficacy and safety for clinical applications.

This pilot study assessed the effectiveness of the intravitreal dexamethasone implant (Ozurdex) in retinal vein occlusion (RVO) patients and explored potential pre-treatment biomarkers to improve management and prognosis. Eighteen patients with branch RVO (BRVO) and twenty-four with central RVO (CRVO) receiving two intravitreal injections of Ozurdex (at baseline and between 4 and 6 months) were included. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded at baseline and after 3, 6, and 12 months. Retinal morphology was assessed using optical coherence tomography (OCT), and serum biomarkers were analyzed by ELISAs. No significant BCVA improvement was observed in RVO patients, while CRT significantly decreased from 3 to 12 months. Patients without defects of the retinal inner layers, ellipsoid zone, and external limiting membrane showed significantly higher BCVA at 6 and 12 months. Both BRVO and CRVO groups demonstrated significant BCVA improvement and CRT reduction at 6 and 12 months, with better outcomes in BRVO patients. These patients exhibited lower baseline serum levels of xanthine oxidase (XO) and thrombospondin-1 (TSP-1), which inversely correlated with BCVA at 12 months. Ozurdex was effective in real-life RVO treatment, particularly in BRVO. Serum XO and TSP-1 may serve as prognostic biomarkers for RVO.

Hyperuricemia is a common metabolic disorder affecting individuals across all age groups and genders. Uric acid is the final oxidation product of purine metabolism, tends to accumulate in the body, and the deposition of monosodium urate and monohydrate crystals in joints and periarticular tissues leads to condition called Gout. Presence of deposition of uric acid crystals and elevated serum uric acid levels is cardinal feature of Gout, which cause severe pain and inflammation in the affected joints. Conventional management includes analgesics, glucocorticoids, and uric acid–lowering therapies such as xanthine oxidase inhibitors and uricosuric agents, yet the condition often remains difficult to manage effectively. In Ayurveda, the clinical presentation of gout closely resembles Vata-Rakta, in which vitiated Vata and Rakta Dosha both localized in multiple joints. This article presents a case study of a 62-year-old male patient presented with complaints of bilateral knee and ankle joint pain, severe swelling of the ankles and right great toe, and elevated serum uric acid levels. He had been experiencing progressive symptoms for three months. For Ayurvedic management, he was administered Shamana Chikitsa with oral medications along with three sittings of Jalaukavcharana (leech therapy) for 21 days. Remarkable improvement was observed, with serum uric acid levels reducing from 11.2 mg/dL to 5.1 mg/dL, accompanied by significant reduction in pain, swelling, discoloration and stiffness. The therapy was carried out without any dietary modifications and no adverse effects were noted during or after treatment. This case demonstrates that Ayurvedic management, combining Shamana Chikitsa and Raktamokshana, can provide effective and safe results in Vata-Rakta (Gout). Observation and results were drawn based on assessment criteria. Discussion was done based on entire observations during research. Conclusion was drawn based on result.

Discovery of 1-(4-cyanopyrimidin-2-yl)-1H-pyrazole-4-carboxylic acids as potent xanthine oxidase inhibitors via molecular cleavage and reassembly of allopurinol as a key strategy.

Gnetum montanum (“”, Gnetaceae), traditionally employed in Vietnam for the treatment of rheumatism, chronic bronchitis, menstrual disorders, and as an antidote, was investigated for xanthine oxidase (XO) inhibitory constituents. Bioassay-guided fractionation led to the isolation of five 2-phenylbenzofurans, including two previously undescribed metabolites, gnetumgam A (1) and gnetumgam B (2), along with gnetifolin M (3), gnetifolin A (4), and gnetumelin B (5). Structures were unambiguously elucidated by comprehensive spectroscopic analyses (1D/2D NMR, HR-ESI-MS) and comparison with reference data. Among these, gnetumgam B (2) and gnetifolin M (3) exhibited notable XO inhibition (IC50 = 111.7 and 113.1 µM, respectively), although less potent than the clinical agents allopurinol and febuxostat. Structure–activity relationship analysis revealed that substitution patterns on the benzyl ring and benzofuran nucleus strongly influenced activity, particularly via interactions within the molybdenum cofactor (MoCo) pocket. Molecular docking and dynamics simulations corroborated the experimental findings and underscored gnetumgam B (2) as a promising scaffold for further optimization toward next-generation XO inhibitors.

ABSTRACT Artemisia selengensis is a medicinal and edible plant, whose tender stems are widely consumed as a folk vegetable in China. However, due to their bitterness, Artemisia selengensis leaves (ASL) are often discarded as a waste material, resulting in resource wastage. This study aimed to characterize ASL's chemical composition, develop a “green” extraction method, and explore its potential bioactivity. Using LC‐MS, 72 compounds were identified. To extract 7 representative caffeoylquinic acids (CQAs), the mixture of choline chloride and ethylene glycol (1:6) was selected as the optimal deep eutectic solvent (DES), and the extraction parameters were optimized as follows: extraction time of 21 min, temperature of 44°C and ultrasonic power of 420 W. Based on molecular docking analysis, both 3,5‐diCQA and 1,5‐diCQA exhibited strong binding affinity to xanthine oxidase (XO), consistent with their potent XO inhibitory effects (IC 50 = 3.69 and 3.35 nmol/mL, respectively). In addition, a greater XO inhibition was observed for the DES extract (IC 50 = 6.05 μg/mL) compared with the methanol extract (IC 50 = 22.5 μg/mL). This study not only helps to reduce ASL disposal's environmental load and boost its agricultural value, but also sets a green model for similar vegetable waste to aid circular agriculture.

Astragalus membranaceus polysaccharide (APs) and Eugenol: Multi-target Anti-inflammatory, Antioxidant, Antimicrobial, and anticancer effects validated by in Silico studies