Xanthine Oxidase Inhibitor Research Articles

Density functional theory (DFT), molecular docking, and xanthine oxidase inhibitory studies of dinaphthodiospyrol S from Diospyros kaki L

In this work, we investigated Diospyros kaki extract and an isolated compound for their potential as xanthine oxidase (XO) inhibitors, a target enzyme involved in inflammatory disorders. The prepared extract was subjected to column chromatography, and dinaphthodiospyrol S was isolated. Then XO inhibitory properties were assessed using a spectrophotometry microplate reader. DMSO was taken as a negative control, and allopurinol was used as a standard drug. The molecular docking study of the isolated compound to the XO active site was performed, followed by visualization and protein–ligand interaction. The defatted chloroform extract showed the highest inhibitory effect, followed by the chloroform extract and the isolated compound. The isolated compound exhibited significant inhibitory activity against XO with an IC50 value of 1.09 µM. Molecular docking studies showed that the compound strongly interacts with XO, forming hydrogen bond interactions with Arg149 and Cys113 and H-pi interactions with Cys116 and Leu147. The binding score of −7.678 kcal/mol further supported the potential of the isolated compound as an XO inhibitor. The quantum chemical procedures were used to study the electronic behavior of dinaphthodiospyrol S isolated from D. kaki. Frontier molecular orbital (FMO) analysis was performed to understand the distribution of electronic density, highest occupied molecular orbital HOMO, lowest unoccupied molecular orbital LUMO, and energy gaps. The values of HOMO, LUMO, and energy gap were found to be −6.39, −3.51 and 2.88 eV respectively. The FMO results indicated the intramolecular charge transfer. Moreover, reactivity descriptors were also determined to confirm the stability of the compound. The molecular electrostatic potential (MEP) investigation was done to analyze the electrophilic and nucleophilic sites within a molecule. The oxygen atoms in the compound exhibited negative potential, indicating that they are favorable sites for electrophilic attacks. The results indicate its potential as a therapeutic agent for related disorders. Further studies are needed to investigate this compound's in vivo efficacy and safety as a potential drug candidate.

The anti-hyperuricemic and gut microbiota regulatory effects of a novel purine assimilatory strain, Lactiplantibacillus plantarum X7022.

Probiotics have been reported to effectively alleviate hyperuricemia and regulate the gut microbiota. The aim of this work was to study the in vivo anti-hyperuricemic properties and the mechanism of a novel strain, Lactiplantibacillus plantarum X7022. Purine content and mRNA expression of purine assimilation related enzymes were determined by HPLC and qPCR, respectively. Hyperuricemic mice were induced by potassium oxonate and hypoxanthine. Uric acid (UA), blood urea nitrogen, creatinine and renal inflammation were examined by kits. The expression of renal UA transporters was subjected to western blotting. Kidney tissues were sectioned for histological analysis. The fecal short-chain fatty acids (SCFAs) were determined by HPLC, and gut microbiota was investigated using the 16S rDNA metagenomic sequencing. L. plantarum X7022 possesses a complete purine assimilation pathway and can exhaust xanthine, guanine, and adenine by 82.1%, 33.1%, and 12.6%, respectively. The strain exhibited gastrointestinal viability as 44% at the dose of 109CFU/mL in mice. After four-week administration of the strain, a significant decrease of 35.5% in the serum UA level in hyperuricemic mice was achieved. The diminished contents of fecal propionate and butyrate were dramatically boosted. The treatment also alleviated renal inflammation and restored renal damage. The above physiological changes may due to the inhibited xanthine oxidase (XO) activity, as well as the expressional regulation of UA transporters (GLUT9, URAT1 and OAT1) to the normal level. Notably, gut microbiota dysbiosis in hyperuricemic mice was improved with the inflammation and hyperuricemia related flora depressed, and SCFAs production related flora promoted. The strain is a promising probiotic strain for ameliorating hyperuricemia.

IDENTIFICATION AND TREATMENT OF ERYTHEMA MULTIFORME INDUCED BY ALLOPURINOL

Introduction: Allopurinol is a xanthine oxidase inhibitor and has become established as the drug of choice for preventing and treating chronic gout. Erythema multiforme (EM) is an immune-mediated reaction that involves the skin and sometimes the mucosa. Many cases of EM are caused by drugs, one of which is allopurinol. The purpose of the case study is to explain the identification of allopurinol as a predisposing factor for EM and how it is treated. Case. A 56-year-old woman came with complaints of scabs on her lips for 1 week ago, and had been treated with corticosteroid ointment for 3 days. Extraoral examination showed hemorrhagic crusts on the upper and lower lips with erosive surrounded by erythematous margins. On the extremity found a target lesion on the right hand. Based on the examination, the patient was diagnosed with Erythema Multiforme with a differential diagnosis of herpes labialis and herpes associated erythema multiforme. Case Management. The therapy in this case was giving antihistamines for 1 week, NaCl 0.9% compresses on the lips for 30 minutes 3 times a day, after 2 weeks of treatment added with the application of 1% hydrocortisone cream as an anti-inflammatory and petroleum jelly on the lips as a moisturizer. Conclusion. Identification of the etiology of this EM case was carried out through anamnesis and history of drugs consumed as well as administration of topical corticosteroids as anti-inflammatories and oral antihistamines to reduce allergic reactions.

Data mining-guided alleviation of hyperuricemia by Paeonia veitchii Lynch through inhibition of xanthine oxidase and regulation of renal urate transporters

BackgroundHyperuricemia (HUA) is a metabolic disease characterized by a high level of uric acid (UA). The extensive historical application of traditional Chinese medicine (TCM) offers a range of herbs and prescriptions used for the treatment of HUA-related disorders. However, the core herbs in the prescriptions and their mechanisms have not been sufficiently explained. PurposeOur current investigation aimed to estimate the anti-HUA effect and mechanisms of Paeonia veitchii Lynch, an herb with high use frequency identified from data mining of TCM prescriptions. MethodsPrescriptions for HUA/gout treatment were statistically analyzed through a data mining approach to determine the common nature and use frequency of their composition herbs. The chemical constituents of Paeonia veitchii extract (PVE) were analyzed by UPLC-QTOF-MS/MS, while its UA-lowering effect was further evaluated in adenosine-induced liver cells and potassium oxonate (PO) and hypoxanthine (HX)-induced HUA mice. ResultsA total of 225 prescriptions involving 246 herbs were sorted out. The properties, flavors and meridians of the appearing herbs were mainly cold, bitter and liver, respectively, while their efficacy was primarily concentrated on clearing heat and dispelling wind. Further usage frequency analysis yielded the top 20 most commonly used herbs, in which PVE presented significant inhibitory activity (IC50 = 131.33 µg/ml) against xanthine oxidase (XOD), and its constituents showed strong binding with XOD in a molecular docking study and further were experimentally validated through XOD enzymatic inhibition and surface plasmon resonance (SPR). PVE (50 to 200 μg/ml) dose-dependently decreased UA levels by inhibiting XOD expression and activity in BRL 3A liver cells. In HUA mice, oral administration of PVE exhibited a significant UA-lowering effect, which was attributed to the reduction of UA production by inhibiting XOD activity and expression, as well as the enhancement of UA excretion by regulating renal urate transporters (URAT1, GLUT9, OAT1 and ABCG2). Noticeably, all doses of PVE treatment did not cause any liver injury, and displayed a renal protective effect. ConclusionsOur results first comprehensively clarified the therapeutic effect and mechanisms of PVE against HUA through suppressing UA production and promoting UA excretion with hepatic and renal protection, suggesting that PVE could be a promising UA-lowering candidate with a desirable safety profile for the treatment of HUA and prevention of gout.

SCREENING FOR ANTI-HYPERURICEMIA POTENTIAL OF SOME INDONESIAN MEDICINAL PLANTS THROUGH XANTHINE OXIDASE INHIBITION IN VITRO ASSAY

Objective: This study aimed to examine the in vitro xanthine oxidase inhibitory activity of 12 plants commonly used as gout medicines by the Indonesian people.
 Methods: The measurement of xanthine oxidase enzyme inhibitory activity was using UV spectrophotometry. The in vitro assessment of xanthine oxidase inhibition activity was tested on extracts from Eleutherine bulbosa (Mill.) Urb. Bulbs, Pandanus amaryllifolius Roxb. leaves, Alyxia reinwardtii Blume stem barks, Ruta angustifolia Pers aerial parts, Dioscorea hispida Dennst tubers, Plantago major L. leaves, Symphytum officinale L. roots, Euphorbia hirta L. aerial parts, Chromolaena odorata L. leaves, Solanum torvum Sw fruits, Peperomia pellucida L. Kunth. aerial parts and Strobilanthes crispa L. Blume leaves.
 Results: The results of this study showed that all tested plant extracts can inhibit xanthine oxidase activity with IC50 values varying from 27.80 µg/ml to 47.14 µg/ml. The IC50 value of allopurinol, used as positive control, was 1.24 µg/ml. Among all the tested plant extracts, Strobilanthes crispa L. Blume leaves extract has the best inhibitory activity against xanthine oxidase enzyme with IC50 value of 27.80 µg/ml.
 Conclusion: Strobilanthes crispa L. Blume leaves extract has the best inhibitory activity against xanthine oxidase, so It has the potential to be developed into herbal medicine to treat hyperuricemia. This study provides scientific support for the anti-hyperuricemia activity of these herbs, which are empirically used to treat gout.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Polyphenol Composition, Antioxidant Capacity and Xanthine Oxidase Inhibition Mechanism of Furong Plum Fruits at Different Maturity Stages.

An experiment was conducted on the polyphenol content, flavonoid content, anthocyanin content, and antioxidant capacity of Furong plum (Prunus salicina Lindl. cv. "furong") at different maturity stages to determine the most suitable maturity stage. The inhibition of plum polyphenols on xanthine oxidase (XOD) was measured, and its kinetics were studied to reveal the inhibitory mechanism. The experimental results showed that the polyphenol, flavonoid and anthocyanin contents of plums at the ripe stage were the highest, reaching 320.46 mg GAE/100 g FW, 204.21 mg/100 g FW, and 66.24 mg/100 g FW, respectively, in comparison those of the plums at the immature and mid-ripe stages. The antioxidant capacity of the ripe plums was stronger than it was during the other stages of the plums growth. Among them, the total polyphenols of the ripe plums exhibited the strongest antioxidant capacity (IC50 values against DPPH and hydroxyl radicals were 28.19 ± 0.67 μg/mL and 198.16 ± 7.55 μg/mL, respectively), which was between the antioxidant capacity of the free polyphenols and bound polyphenols. The major phenolic monomer compounds of plum polyphenols were flavan-3-ols (epicatechin, catechin, proanthocyanidin, and procyanidin B2), flavonols (myricetin), and phenolic acids (chlorogenic acid, ferulic acid, and protocatechuic acid). Additionally, plum polyphenols exhibited a strong inhibitory effect on XOD, with an IC50 value of 77.64 μg/mL. The inhibition kinetics showed that plum polyphenols are mixed-type inhibitors that inhibit XOD activity and that the inhibition process is reversible. The calculated values of Ki and α were 16.53 mmol/L and 0.26, respectively.

Anti-hyperuricemic properties and mechanism of Lactiplantibacillus plantarum X7023

The study conducted on Lactiplantibacillus plantarum X7023, a novel strain isolated from stinky tofu brine, aimed to investigate its effects on hyperuricemia. The strain demonstrated high in vitro gastrointestinal survivability and purine-lowering ability (guanine, xanthine and adenine decreased by 21.4%, 93.9% and 11.5%, respectively). The anti-hyperuricemia effects of the strain have been studied in potassium oxonate and hypoxanthine induced hyperuricemia mice. The serum uric acid (UA) levels of hyperuricemic mice were significantly reduced by 38.8% and 19.0% after treatment with low and high dose of L. plantarum X7023 treatment, respectively. Additionally, the levels of creatinine and blood urea nitrogen were decreased by 19.6% and 21.2% respectively in low dose of L. plantarum X7023 group. The anti-hyperuricemic mechanism of L. plantarum X7023 might be its inhibiting xanthine oxidase (XOD) activity, and regulating the expression of renal UA transporters. According to kidney inflammatory cytokines and histopathological analysis, L. plantarum X7023 could also alleviate the kidney inflammation and protect the kidney. Therefore, L. plantarum X7023 is a potential probiotic strain for the amelioration of hyperuricemia. This study further demonstrated that there are significant correlations among UA level, oxidative stress, kidney inflammation, XOD activity and UA transporter expressions in hyperuricemic mice.

Comparative analysis of phenolic content and in vitro bioactivities of Bidens pilosa L. flowers and leaves as affected by extraction solvents

Bidens pilosa L., native to South America, is valued for its purposes as a food and medicine. The study aimed to examine phenolics, antioxidant activity and inhibitory effects of B. pilosa flower and leaf extracts on albumin denaturation, α-glucosidase, α-amylase, xanthine oxidase, and tyrosinase. The choice of extractants (water, methanol, acetone, and ethyl acetate) greatly influenced the phenolic content and bioactivities of the extracts. The results demonstrated the flower and leaf extracts differed significantly with respect to total phenolic content and abilities to inhibit albumin denaturation, α-amylase, and xanthine oxidase. The ethyl acetate extracts may show the strongest activity to scavenge DPPH radicals, to inhibit α-amylase and α-glucosidase, and to protect albumin against denaturation. The aqueous extract possessed the strongest capacity to inhibit xanthine oxidase while the acetonic extract was more effective in suppressing tyrosinase compared to the others.

Allopurinol versus Febuxostat: A New Approach for the Management of Hepatic Steatosis in Metabolic Dysfunction-Associated Steatotic Liver Disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) includes patients with hepatic steatosis and at least one of five cardiometabolic risk factors. Xanthine oxidase (XO) represents a treatment target for MASLD. We aimed to evaluate the effect of two xanthine oxidase inhibitors, allopurinol and febuxostat, plus lifestyle modifications compared to lifestyle modifications alone on improving steatosis. Ninety MASLD patients were assigned to one of three groups for three months. Patients with hyperuricemia were given either allopurinol 100 mg or febuxostat 40 mg daily, along with lifestyle modifications. The third control group was only given lifestyle modifications, excluding all patients with hyperuricemia due to ethical concerns. The primary outcome was to measure the change in the controlled attenuation parameter (CAP) score as an indicator of steatosis from baseline after three months. The secondary outcome was to measure the change in serum uric acid (SUA) three months from baseline. The study found that the CAP score decreased significantly in the allopurinol group (p = 0.009), but the decline in the febuxostat or lifestyle groups was non-significant (p = 0.189 and 0.054, respectively). The SUA levels were significantly reduced in both the allopurinol and febuxostat groups (p < 0.001), with no statistical difference between the two groups (p = 0.496).

Amelioration of hyperuricemia by Lactobacillus acidophilus F02 with uric acid-lowering ability via modulation of NLRP3 inflammasome and gut microbiota homeostasis

Hyperuricemia is a metabolic disease caused by disturbances in purine metabolism and imbalances in the formation and excretion of uric acid. It is closely related to the gut microbiota, which is considered a therapeutic target. Some lactic acid bacteria with a uric acid lowering effect have the potential to ameliorate hyperuricemia in the host. However, the mechanism of action remains unclear. Here, we screened a strain of Lactobacillus acidophilus F02 that efficiently degrades uric acid precursors (inosine and guanosine) and further investigated its underlying mechanism on the alleviation of hyperuricemia in high fructose-adenine induced mice. Results showed that L. acidophilus F02 administration reduced serum uric acid levels in hyperuricemia mice by inhibiting xanthine oxidase and adenosine deaminase activity, while protecting hepatorenal injury and systemic inflammation by regulating the relative expression of NLRP3 inflammasome. Most importantly, it restored gut microbial homeostasis and the abundance of bacterial taxa (i.e., a balance in the relative abundance of Firmicutes and Actinobacteria and an increase in the abundance of Bacteroides, Ruminococcus and Lactobacillus). Furthermore, the ability of L. acidophilus F02 to lower uric acid and suppress NLRP3 inflammasome expression was confirmed in the HK-2 cell model, as well as the multiple immunomodulatory effects on RAW264.7 cells. Taken together, we speculate that fructose-adenine induced hyperuricemia triggers hepatorenal injury and gut microbiota dysbiosis, which is ameliorated by L. acidophilus F02. Collectively, the results suggest that lowering uric acid synthesis, increasing uric acid excretion and reducing NLRP3-related IL-1β levels are effective strategies to ameliorate hyperuricemia. Such information could inform future studies on the ecology of L. acidophilus and guide the use of this species for dietary applications in the food industry.

Phytochemical profiling and evaluation of the anti-aging and anti-inflammatory potential of cultivated Eclipta alba (L.)

Natural products are increasingly studied for pharmaceutical and cosmetic applications. In our continuing search for new natural active ingredients for cosmetic uses, we investigated the phytochemistry and studied the bioactivity of Eclipta alba (L.) cultivated in center-Val de Loire Region (CVLR) in France to develop a new anti-aging active ingredient. This plant is known as the false daisy and is traditionally used in Ayurveda for the treatment of digestive, respiratory, hepatic, and cutaneous disorders and for its activity as a hair growth promoter.To highlight the compounds involved in different bioactivities, a metabolomic study of the plant was undertaken. The extract of the aerial parts, obtained by ultrasound-assisted extraction in ethanol, was tested for antioxidant activity and for its inhibitory effect on various enzymes involved in skin aging. The raw extract was fractionated using liquid/liquid extraction (LLE) and Centrifugal Partition Chromatography (CPC), then fraction activity was evaluated to target the main active compounds. HRMS/MS and NMR were used to identify the compounds contained in the active fractions.Some fractions had showed strong collagenase, cyclooxygenase-2 (COX-2) and xanthine oxidase (XO) inhibition. The two most active fractions contained mostly coumestans (demethylwedelolactone (DWL) and wedelolactone (WL)), and other phenolic compounds present in lower amount, which were identified as carriers of the anti-collagenase, anti-cyclooxygenase 2 and anti-xanthine oxidase activity.Therefore, this study suggested that Eclipta alba grown in CVLR has a phytochemistry in line with the description reported in literature and is highly composed of coumestans, phenolic compounds and saponins. The ethanolic extract has shown anti-inflammatory and antioxidant activity and for the first time an anti-collagenase activity has been demonstrated. These activities have been correlated with the presence of wedelolactone (WL) and demethylwedelolactone (DWL), the two majors’ compounds, and other phenolics compounds. Thus, Eclipta alba (L.) cultivated in CVLR could be used as an interesting antioxidant and anti-aging agent for cosmetical applications.